Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Grazoprevir · 19 trials · 6 indications
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (\<LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.
The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid \[RNA\] level below the lower limit of quantification \[LLoQ\] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.
An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid \[RNA\] \< Lower Limit of Quantification \[LLOQ\] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
SVR12 is defined as HCV ribonucleic acid (RNA) less than the lower limit of quantification (\<LLOQ, 15 IU/mL) 12 weeks after the end of all study therapy. A4+B4: GT3 NC TN MK-3682B (8 weeks) arm includes both participants from Part A and Part B who received equivalent dose of MK-3682B.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Part C in the table below combines all (eight) participants from the four distinct arms of Part A who relapsed and were subsequently treated with MK-3682B + RBV for 16 weeks.
The percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) \< Lower Limit of Quantification (LLoQ) 12 weeks after completing treatment (i.e., SVR12) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® Taqman quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, v2.0, which had a lower limit of quantification (LLoQ) of 1.2 Log IU/mL (15 IU/mL) and a lower limit of detection (LLoD) below 15 IU/ml (no specific value). SVR12 was defined as undetectable HCV RNA (target not detected) at 12 weeks after the end of all study therapy. The Clopper-Pearson method was used to construct 95% confidence intervals (CIs) for the SVR12 rate. The lower limit of the 95% CI was compared to the reference rate of 75%; a lower CI limit that was higher than the reference rate would confirm the primary hypothesis and indicate that that the treatment combination was efficacious. As pre-specified in the protocol, only the Immediate Treatment Arm of Part 2 (treatment naïve participants) was included in the primary efficacy analysis.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through Follow-up Week 4 (FUWK4).
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period through FUWK4.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, was also an AE. The primary safety evaluation was limited to the initial treatment period and first 4 follow-up weeks, and the primary safety statistical analysis compared the percentage of participants with events between the Part 2 Immediate Treatment Arm and the Part 2 Deferred Treatment Arm while receiving placebo.
The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) \<15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, \<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group.
SVR12 was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) \<25 IU/mL, either target detected but unquantifiable (TD\[u\]) or target not detected (TND), at 12 weeks after the end of all study therapy. The percentage of participants with SVR12 and accompanying 95% confidence intervals (CIs) were reported for each treatment arm in the Per-Protocol (PP) Population.
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The investigator determined the relationship of the AE to the treatment as unrelated or possibly, probably, or definitely related.
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Data are presented according to actual treatment duration (12 weeks or 24 weeks) regardless of participants' initial arm assignment.
Hepatitis C virus ribonucleic acid (HCV RNA) was measured using the Roche COBAS™ Taqman™ HCV Test, v2.0® assay, which has a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL. SVR12 was defined as HCV RNA \<25 IU/mL (either target detected, unquantifiable or target not detected) 12 weeks after the end of all study therapy.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol -specified procedure, whether or not considered related to the medicinal product or protocol -specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL (in plasma). cEVR was defined as undetectable HCV RNA (target not detected \[TND\]) at Week 12. 95% confidence intervals provided based on the Clopper-Pearson method.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.
Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.
C(H)Xhr of GZR was expressed as liver concentration (μmol GZR/L liver) using the concentration of the extracted liver sample (mass of the liver biopsy/0.2 mL solvent), and assuming that liver has the specific gravity of water (1 g/mL). The arithmetic mean C(H)Xhr concentration is based on the means of 4 FNA passes per participant in all 4 participants.
t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)
Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma AUC0-24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Cmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Blood samples were collected at pre-dose, and from 0.5 to 24 hours post-dose on Days 1 and 10 in order to determine the plasma Tmax of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Blood samples were collected at 24 hours post-dose on Day 1 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
Blood samples were collected at 24 hours post-dose on Day 10 in order to determine the plasma C24 of Grazoprevir. Classification of HI based on the Child-Pugh scale, where a score of 5-6 = Mild HI; a score of 7-9 = Moderate HI; and a score of 10-15 = Severe HI.
An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
| Arm | Type | Description |
|---|---|---|
| Immediate Treatment Group (ITG): Grazoprevir/Elbasvir | EXPERIMENTAL | Participants receive a grazoprevir/elbasvir FDC tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and are followed-up for 24 weeks to Week 36. |
| Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir | PLACEBO_COMPARATOR | Participants receive a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants receive open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants are then followed-up for 24 weeks to Week 52. |
| Immediate Treatment | EXPERIMENTAL | Participants will take grazoprevir 100 mg + elbasvir 50 mg once daily during the 12-week treatment period and then will be monitored for safety during a 24-week follow-up period. |
| Deferred Treatment | PLACEBO_COMPARATOR | Participants will take placebo tablets once daily during the 12-week treatment period and will then be monitored for safety during a 4-week follow-up period. Participants will then begin open-label treatment with grazoprevir 100 mg + elbasvir 50 mg for a 12-week treatment period and will then be monitored for safety during a 24-week follow-up period. |
| Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks | EXPERIMENTAL | TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks. |
| Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks | EXPERIMENTAL | TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. |
| Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks | EXPERIMENTAL | TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. |
| Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks | EXPERIMENTAL | TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. |
| Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks | EXPERIMENTAL | TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks. |
| A1: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 weeks) | EXPERIMENTAL | In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (300 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. |
| A2: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 weeks) | EXPERIMENTAL | In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (300 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. |
| A3: GT3 NC TN Grazoprevir+Uprifosbuvir+Elbasvir (8 weeks) | EXPERIMENTAL | In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (450 mg) + elbasvir (50 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. |
| A4/B4: GT3 NC TN Grazoprevir+Uprifosbuvir+Ruzasvir (8 weeks) | EXPERIMENTAL | Participants will be randomized to either Part A or Part B. In Part A, HCV GT3-infected NC TN participants will take grazoprevir (100 mg) + uprifosbuvir (450 mg) + ruzasvir (60 mg) q.d. by mouth for 8 weeks. In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. Part A participants who relapsed following completion of therapy were offered the option of retreatment with 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. and RBV (weight-based dosing) b.i.d. by mouth for 16 weeks during Part C. |
| B5: GT3 NC TN MK-3682B + RBV (8 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. |
| B6: GT3 NC TN MK-3682B (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. |
| B7: GT3 NC TN MK-3682B + RBV (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. |
| B8: GT3 NC TE MK-3682B (8 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. |
| B9: GT3 NC TE MK-3682B + RBV (8 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 8 weeks. |
| B10: GT3 NC TE MK-3682B (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. |
| B11: GT3 NC TE MK-3682B + RBV (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682 FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. |
| B12: GT3 NC TE MK-3682B (16 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected NC TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. |
| B13: GT3 C TN MK-3682B (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. |
| B14: GT3 C TN MK-3682B + RBV (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. |
| B15: GT3 C TN MK-3682B (16 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. |
| B16: GT3 C TE MK-3682B (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. |
| B17: GT3 C TE MK-3682B + RBV (12 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 12 weeks. |
| B18: GT3 C TE MK-3682B (16 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 16 weeks. |
| B19: GT3 C TE MK-3682B + RBV (16 weeks) | EXPERIMENTAL | In Part B, HCV GT3-infected C TE participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d., and RBV (weight-based dosing) b.i.d., by mouth for 16 weeks. |
| B20: GT4 NC TN MK-3682B (8 weeks) | EXPERIMENTAL | In Part B, HCV GT4-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 8 weeks. |
| B21: GT5 NC TN MK-3682B (12 weeks) | EXPERIMENTAL | In Part B, HCV GT5-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. |
| B22: GT6 NC TN MK-3682B (12 weeks) | EXPERIMENTAL | In Part B, HCV GT6-infected NC TN participants will take 2 MK-3682B FDC tablets (each containing grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg) q.d. by mouth for 12 weeks. |
| A1: GT1 NC GZR+UPR+EBR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. |
| A2: GT1 NC GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. |
| A3: GT2 NC GZR+UPR+EBR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. |
| A4: GT2 NC GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. |
| A5: GT1 NC GZR+UPR+EBR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. |
| A6: GT1 NC GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. |
| B7: GT2 NC GZR+UPR+EBR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. |
| A8: GT2 NC GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. |
| B9: GT1 NC GZR+UPR+RZR (12 weeks) | EXPERIMENTAL | In Part B, HCV GT1-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. |
| B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV | EXPERIMENTAL | In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight. |
| B11: GT2 NC GZR+UPR+RZR (12 weeks) | EXPERIMENTAL | In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. |
| B12: GT1 C GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part B, HCV GT1-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. |
| B13: GT1 C GZR+UPR+RZR (12 weeks) | EXPERIMENTAL | In Part B, HCV GT1-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. |
| B14: GT2 C GZR+UPR+RZR (12 weeks) | EXPERIMENTAL | In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. |
| B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV | EXPERIMENTAL | In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight. |
| B16: GT2 C GZR+UPR+RZR (16 weeks) | EXPERIMENTAL | In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks. |
| B6: GT1 NC GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part B, HCV GT1-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. |
| B8: GT2 NC GZR+UPR+RZR (8 weeks) | EXPERIMENTAL | In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. |
| Part 1 Grazoprevir 50 mg + Elbasvir | EXPERIMENTAL | Non-cirrhotic participants take 50 mg grazoprevir in combination with 50 mg elbasvir by mouth (p.o.) once daily (q.d.) for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| Part 1 Grazoprevir 100 mg + Elbasvir | EXPERIMENTAL | Non-cirrhotic participants take 100 mg grazoprevir in combination with 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 1 and are followed-up for 24 weeks during the open-label period of Part 1. |
| Part 2 Non-cirrhotic Immediate: Grazoprevir + Elbasvir | EXPERIMENTAL | Non-cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2 and are followed-up for 24 weeks during the open-label period of Part 2. |
| Part 2 Non-cirrhotic Deferred: Placebo► Grazoprevir + Elbasvir | PLACEBO_COMPARATOR | Non-cirrhotic participants take dose-matched placebo p.o. q.d. for 12 weeks during the blinded period of Part 2 followed by a 4-week follow-up. Afterwards, participants take grazoprevir (50 mg or 100 mg dose selected from Part I) and 50 mg elbasvir p.o. q.d. for 12 weeks and are followed-up for 24 weeks during the open-label period of Part 2. |
| Part 2 Cirrhotic: Grazoprevir + Elbasvir | EXPERIMENTAL | Cirrhotic participants take grazoprevir (50 mg or 100 mg dose selected from Part 1) and 50 mg elbasvir p.o. q.d. for 12 weeks during the blinded period of Part 2, and are followed-up for 24 weeks during the open-label period of Part 2. |
| GT1:NC Grazoprevir/Elbasvir+SOF 4wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). |
| GT1:NC Grazoprevir/Elbasvir+SOF 6wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). |
| GT1:C Grazoprevir/Elbasvir+SOF 6wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). |
| GT1:C Grazoprevir/Elbasvir+SOF 8wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). |
| GT3:NC Grazoprevir/Elbasvir+SOF 8wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). |
| GT3:NC Grazoprevir/Elbasvir+SOF 12wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). |
| GT3:C Grazoprevir/Elbasvir+SOF 12wk | EXPERIMENTAL | Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned). |
| GZR 100 mg + EBR 50 mg + RBV for 12 weeks | EXPERIMENTAL | Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks |
| Part A: CP-B GZR 50 mg + EBR 50 mg | EXPERIMENTAL | CP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks. |
| Part A: NC GZR 100 mg + EBR 50 mg | EXPERIMENTAL | NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. |
| Part B: CP-B GZR 100 mg + EBR 50 mg | EXPERIMENTAL | CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. |
| Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg | EXPERIMENTAL | CP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm). |
| Intensive PK | EXPERIMENTAL | Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing. |
| GT2: Grazoprevir + Elbasvir + RBV (Arm A1) | EXPERIMENTAL | During Part A of the study, GT2 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks. |
| GT2: Grazoprevir + RBV (Arm B1) | EXPERIMENTAL | During Part B of the study, GT2 participants will receive 100 mg grazoprevir + standard weight-based dosing of RBV for 12 weeks. |
| GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2) | EXPERIMENTAL | During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks. |
| GT 4,5,6: Grazoprevir + Elbasvir (Arm B3) | EXPERIMENTAL | During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir for 12 weeks. |
| A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk | EXPERIMENTAL | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | EXPERIMENTAL | GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-12 wk | EXPERIMENTAL | GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
| B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | EXPERIMENTAL | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg-12 wk | EXPERIMENTAL | GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
| B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant |
| B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
| B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| B7: TN C Grazoprevir 100 mg + Elbasvir 50 mg-18 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks |
| B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| B9: NR Grazoprevir 100 mg + Elbasvir 50 mg-12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
| B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| B11: NR Grazoprevir 100 mg + Elbasvir 50 mg-18 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks |
| B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg-12 wk | EXPERIMENTAL | GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks |
| C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk | EXPERIMENTAL | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight. |
| C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-8 wk | EXPERIMENTAL | GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks |
| D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk | EXPERIMENTAL | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk | EXPERIMENTAL | GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight |
| Grazoprevir 100 mg + RBV 12 Weeks | EXPERIMENTAL | Grazoprevir 100 mg tablet once per day by mouth for 12 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 12 weeks. Participants with detectable HCV RNA at TW4 received an additional 12 weeks of study therapy for a total of 24 weeks of treatment. |
| Grazoprevir 100 mg + RBV 24 Weeks | EXPERIMENTAL | Grazoprevir 100 mg tablet once per day by mouth for 24 weeks and RBV capsules twice per day by mouth at a total daily dose from 800 to 1400 mg based on participant weight for 24 weeks. |
| Grazoprevir 25 mg + PEG-IFN + RBV | EXPERIMENTAL | After a maximum of a 45 day screening window, randomized participants receive 25 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by Response Guided Therapy (RGT). Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their Hepatitis C virus ribonucleic acid (HCV RNA) level at Treatment Week (TW) 4. |
| Grazoprevir 50 mg + PEG-IFN + RBV | EXPERIMENTAL | After a maximum of a 45 day screening window, randomized participants receive 50 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Grazoprevir 100 mg + PEG-IFN + RBV | EXPERIMENTAL | After a maximum of a 45 day screening window, randomized participants receive 100 mg grazoprevir in combination with PEG-IFN and RBV for 12 weeks followed by 24 weeks of follow-up as determined by RGT. Participants may receive an additional 12 weeks of PEG-IFN plus RBV depending on their HCV RNA level at TW 4. |
| Grazoprevir 100 mg | EXPERIMENTAL | TN non-cirrhotic (NC) participants receive Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. |
| Grazoprevir 200 mg | EXPERIMENTAL | TN NC participants receive Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. |
| Grazoprevir 400 mg | EXPERIMENTAL | TN NC participants receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. |
| Grazoprevir 800 mg | EXPERIMENTAL | TN NC participants receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. |
| Boceprevir 800 mg | ACTIVE_COMPARATOR | TN NC participants start a 4 week lead-in with Peg-IFN + RBV, then receive Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy. |
| Grazoprevir 400 mg/100 mg | EXPERIMENTAL | As the result of an interim analysis, TN NC participants assigned to the 400 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study. |
| Grazoprevir 800 mg/100 mg | EXPERIMENTAL | As the result of an interim analysis, TN NC participants assigned to the 800 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study. |
| OL Grazoprevir 100 mg | EXPERIMENTAL | TN cirrhotic participants receive open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. |
| Participants with End Stage Renal Disease on Hemodialysis | EXPERIMENTAL | Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.. |
| Participants with Severe Renal Impairment | EXPERIMENTAL | Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. |
| Healthy Participants | EXPERIMENTAL | Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. |
| Part 1-Mild Hepatic Impairment (HI) | EXPERIMENTAL | Participants with mild hepatic impairment will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study. |
| Part 1-Healthy Matched to Mild HI | EXPERIMENTAL | Healthy participants will receive 200 mg of Grazoprevir once a day for 10 consecutive days during Part 1 of the study. |
| Part 2-Moderate HI | EXPERIMENTAL | Participants with moderate hepatic impairment will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study. |
| Part 2-Healthy Matched to Moderate HI | EXPERIMENTAL | Healthy participants will receive 100 mg of Grazoprevir once a day for 10 consecutive days during Part 2 of the study. |
| Part 3-Severe HI | EXPERIMENTAL | Participants with severe hepatic impairment will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study. |
| Part 3-Healthy Matched to Severe HI | EXPERIMENTAL | Healthy participants will receive 50 mg of Grazoprevir once a day for 10 consecutive days during Part 3 of the study. |
| 400 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 400 mg Grazoprevir or Placebo |
| 600 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 600 mg Grazoprevir or Placebo |
| 800 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 800 mg Grazoprevir or Placebo |
| 400 mg Grazoprevir - GT3 | EXPERIMENTAL | GT3 HCV-infected Participants: 400 mg Grazoprevir or Placebo |
| 600 mg Grazoprevir - GT3 | EXPERIMENTAL | GT3 HCV-infected Participants: 600 mg Grazoprevir or Placebo |
| 800 mg Grazoprevir - GT3 | EXPERIMENTAL | GT3 HCV-infected Participants: 800 mg Grazoprevir or Placebo |
| 200 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 200 mg Grazoprevir or Placebo |
| 100 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 100 mg Grazoprevir or Placebo |
| 50 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 50 mg Grazoprevir or Placebo |
| 200 mg Grazoprevir - GT3 | EXPERIMENTAL | GT3 HCV-infected Participants: 200 mg Grazoprevir or Placebo |
| 100 mg Grazoprevir - GT3 | EXPERIMENTAL | GT3 HCV-infected Participants: 100 mg Grazoprevir or Placebo |
| 50 mg Grazoprevir - GT3 | EXPERIMENTAL | GT3 HCV-infected Participants: 50 mg Grazoprevir or Placebo |
| 30 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 30 mg Grazoprevir or Placebo |
| 10 mg Grazoprevir - GT1 | EXPERIMENTAL | GT1 HCV-infected Participants: 10 mg Grazoprevir or Placebo |
| Name | Type | Description |
|---|---|---|
| Grazoprevir/Elbasvir | DRUG | FDC tablet containing 100 mg of grazoprevir and 50 mg of elbasvir taken q.d. by mouth for 12 weeks. |
| Placebo | DRUG | Placebo tablet matching grazoprevir/elbasvir FDC tablet taken q.d. by mouth for 12 weeks. |
| Grazoprevir + Elbasvir | DRUG | FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth. |
| Grazoprevir | DRUG | GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning. |
| Elbasvir | DRUG | EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning. |
| Ribavirin | DRUG | RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight). |
| Sofosbuvir | DRUG | SOF 400 mg tablet taken q.d. by mouth in the morning with food. |
| Uprifosbuvir | DRUG | Part A: two or three uprifosbuvir 150 mg (300 or 450 mg total daily dose) tablets taken q.d. by mouth. |
| Ruzasvir | DRUG | Part A: six ruzasvir 10 mg (60 mg total daily dose) capsules taken q.d. by mouth. |
| MK-3682B | DRUG | Part B and Part C: two FDC tablets, each containing grazoprevir 50 mg + elbasvir 225 mg + ruzasvir 30 mg, taken q.d. by mouth. |
| Ribavirin (RBV) | DRUG | Part B and Part C: RBV 200 mg capsules taken b.i.d. by mouth at a total daily dose of 800 mg - 1400 mg based on participant body weight. |
| Uprifosbuvir (+) Grazoprevir (+) Ruzasvir | DRUG | Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth. |
| Placebo to Grazoprevir | DRUG | One tablet of placebo matched to grazoprevir, taken orally once daily for 12 weeks. |
| Placebo to Elbasvir | DRUG | One tablet of placebo matched to elbasvir, taken orally once daily for 12 weeks. |
| Grazoprevir/Elbasvir FDC | DRUG | FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth. |
| Grazoprevir (GZR) | DRUG | 100 mg oral tablet (total daily dose) |
| Elbasvir (EBR) | DRUG | 10 mg oral capsule (total daily dose = 5 capsules) |
| MK-5172A | DRUG | MK-5172A FDC tablet containing GZR 100 mg + EBR 50 mg taken q.d. by mouth. |
| pegylated interferon alfa-2b | BIOLOGICAL | 1.5 mcg/kg/week, administered as a weekly subcutaneous (SC) injection |
| Boceprevir | DRUG | Four 200 mg capsules orally three times daily. |
| Placebo for Grazoprevir | DRUG | Orally once daily in AM. |
| Placebo for Boceprevir | DRUG | Four capsules orally three times daily. |
| Peg-interferon alfa-2b | DRUG | 1.5 μg/kg/week subcutaneous injection. |
Inclusion Criteria: * Has documented chronic HCV GT1, GT4, or GT6 (with no evidence of non-typeable or mixed genotype) infection * Meets clinical criteria for presence or absence of cirrhosis based on liver disease staging assessment * Is abstinent or uses acceptable method(s) of contraception Exc...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Atea Pharmaceuticals, Inc. | AVIR | 2 | PHASE3 | Bemnifosbuvir-Ruzasvir, Sofosbuvir-Velpatasvir |
| Abbott Laboratories | ABT | 2 | - | Undisclosed |
| AbbVie, Inc. | ABBV | 1 | - | Undisclosed |
Grazoprevir is an investigational small molecule being developed for the treatment of Hepatitis C Virus infection, including chronic Hepatitis C. It is being studied in combination with other antiviral agents such as elbasvir and with peginterferon and ribavirin. The drug is currently in Phase 2 clinical development.
Grazoprevir is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with chronic Hepatitis C infection.
Grazoprevir is currently in Phase 2 clinical development. It has completed 13 clinical trials with a total enrollment of 2,989 participants. The drug is investigational and has not been approved by regulatory authorities for any indication.
Grazoprevir has been studied in several completed clinical trials, including NCT01353911, which evaluated the drug with peginterferon and ribavirin in treatment-naïve patients with chronic Hepatitis C. Other trials include NCT01710501, NCT01937975, and NCT02105467, which studied different dosing regimens and combinations.
Yes, Grazoprevir is also known as MK-5172. Clinical trial records refer to the drug by both names, such as in the study titled 'Grazoprevir (MK-5172) Administered With Peginterferon and Ribavirin in Treatment-Naïve Participants With Chronic Hepatitis C.'