Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Vaniprevir · 8 trials · 3 indications
SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
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 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 product, was also an AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
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 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 product, was also an AE.
SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.
An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the 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 product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted "Tier 1" safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea).
Rapid viral response (RVR) is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) at Week 4. Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The limit of quantification was 1.2 log IU/mL (15 IU/mL) and the limit of detection was \<1.2 log IU/mL, but with no specific value. The Data-As-Observed (DAO) approach was used to handle missing data.
The percentage of non-cirrhotic participants with undetectable Hepatits C virus (HCV) ribonucleic acid (RNA) 24 weeks after completing treatment was determined for each Vaniprevir 600 mg b.i.d. and control regimen. Results for Vaniprevir 300 mg are presented as a Secondary Outcome Measure.
The number of non-cirrhotic participants experiencing AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen. An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product.
The number of non-cirrhotic participants withdrawing from study treatment due to AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen.
Rapid Viral Response (RVR) was declared if Hepatitis C Virus (HCV) ribonucleic acid (RNA) was undetectable at Week 4.
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 study therapy, whether or not considered related to the use of the product.
Liver samples were collected by FNA at 3 of 5 of the following specified postdose timepoints: 3, 12, 24, 48 and 72 hours after a single vaniprevir dose on Day 7. The technical success of the FNA procedure was established for a participant if vaniprevir was detected from at least 2 of the 3 FNA collection timepoints.
Participants were administered a single dose of vaniprevir; then their blood was collected at the following time points: 0.5, 1, 1.5, 2, 3, 4, 8, 12, 16, 24, 32 and 48 hours postdose. The AUC (0-infinity) of vaniprevir in blood plasma was based on an analysis of covariance (ANCOVA) model used to analyze natural log-transformed values that were back-transformed to derive geometric least-squares mean and confidence interval.
| Arm | Type | Description |
|---|---|---|
| Vaniprevir 24 Week Arm | EXPERIMENTAL | Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment |
| Vaniprevir 12 Week Arm | EXPERIMENTAL | Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV |
| Control Arm | ACTIVE_COMPARATOR | Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV. |
| Vaniprevir 200 mg + peg-IFN + ribavirin | EXPERIMENTAL | Participants will receive vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Vaniprevir 600 mg + peg-IFN + ribavirin | EXPERIMENTAL | Participants will receive vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Vaniprevir 1200 mg + peg-IFN + ribavirin | EXPERIMENTAL | Participants will receive vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Placebo + peg-IFN + ribavirin | PLACEBO_COMPARATOR | Participants will receive placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| 24-wk Vaniprevir 600 mg + Peg-IFN/RBV | EXPERIMENTAL | Vaniprevir 600 mg (total daily dose) and RBV (1000 mg or 1200 mg total daily dose based on body weight) twice daily (b.i.d.) and Peg-IFN 180 mcg injection once weekly for 24 weeks. |
| 24-wk Vaniprevir 600 mg + 24-wk PBO + Peg-IFN/RBV | EXPERIMENTAL | Vaniprevir 600 mg (total daily dose) and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 24 weeks, followed by PBO and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for an additional 24 weeks. |
| 48-wk Vaniprevir 300 mg + Peg-IFN/RBV | EXPERIMENTAL | Vaniprevir 300 mg (total daily dose, taken once daily \[q.d.\]) and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks. |
| 48-wk Vaniprevir 600 mg + Peg-IFN/RBV | EXPERIMENTAL | Vaniprevir 600 mg and RBV (1000 mg or 1200 mg based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks. |
| 48-wk PBO + Peg-IFN/RBV | PLACEBO_COMPARATOR | PBO and RBV (1000 mg or 1200 mg based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks. |
| Placebo + Peg-IFN/Ribavirin | PLACEBO_COMPARATOR | Participants took double-blind Placebo + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. |
| Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin | EXPERIMENTAL | Participants took double-blind Vaniprevir 300 mg twice daily (b.i.d.) + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. |
| Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin | EXPERIMENTAL | Participants took double-blind Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. |
| Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin | EXPERIMENTAL | Participants took double-blind Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. |
| Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin | EXPERIMENTAL | Participants took double-blind Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. |
| Vaniprevir 600 mg | EXPERIMENTAL | Participants received 600 mg vaniprevir only on days 1-7, and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10. |
| Vaniprevir 600 mg + Peg-IFN + RBV | EXPERIMENTAL | Participants received 600 mg vaniprevir on Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10. |
| Vaniprevir 300 mg + Peg-IFN + RBV | EXPERIMENTAL | Participants received 300 mg vaniprevir from Days 1-7; Peg-IFN alpha-2b once a week, RBV daily from Day 1 up to Day 21; and had postdose liver biopsy done by FNA and CNB from Day 7 up to Day 10. |
| Mild Hepatic Insufficiency (HI) | EXPERIMENTAL | Participants with mild hepatic insufficiency (HI) administered a single 300 mg oral tablet of vaniprevir |
| Healthy Control to Mild HI | EXPERIMENTAL | Healthy, matched to mild HI, control participants administered a single 300 mg oral tablet of vaniprevir |
| Moderate HI | EXPERIMENTAL | Participants with moderate HI administered a single 300 mg oral tablet of vaniprevir |
| Healthy Control to Moderate HI | EXPERIMENTAL | Healthy, matched to moderate HI, control participants administered a single 300 mg oral tablet of vaniprevir |
| Severe HI | EXPERIMENTAL | Participants with severe HI administered a single 200 mg oral tablet of vaniprevir |
| Healthy Control to Severe HI | EXPERIMENTAL | Healthy, matched to severe HI, control participants administered a single 200 mg oral tablet of vaniprevir |
| Name | Type | Description |
|---|---|---|
| Vaniprevir | DRUG | Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 24 weeks |
| peg-IFN | BIOLOGICAL | Open-label peg-IFN alfa-2b at 1.5 μg/kg once per week, administered subcutaneously (SC) for 24 weeks |
| ribavirin | DRUG | Capsules containing 200 mg RBV, orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 weeks |
| Placebo to vaniprevir | DRUG | Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks |
| Pegylated Interferon (peg-IFN) | DRUG | Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks |
| Comparator: Placebo | DRUG | Placebo to vaniprevir oral capsule twice daily for 28 days |
| Ribavirin (RBV) | DRUG | Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing \<=75 kg and 1200 mg for participants weighing \>75 kg. |
| Placebo (PBO) | DRUG | Participants took PBO capsules matching Vaniprevir capsules, three in the morning and three in the evening, for 24 or 48 weeks. |
| Comparator: Vaniprevir | DRUG | Vaniprevir 300 mg b.i.d., 600 mg b.i.d., 600 mg q.d., or 800 mg q.d.; duration of treatment: 28 days |
| Comparator: Pegylated-Interferon (Peg-IFN) | DRUG | Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks |
| Comparator: Ribavirin | DRUG | Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks |
| Vaniprevir 600 mg | DRUG | Vaniprevir capsules, were administered orally, twice per day (BID) to achieve a final daily dose of 600 mg on Days 1 through 6; and a single dose of 600 mg, orally, on Day 7. |
| Peg-IFN alfa-2b | BIOLOGICAL | Peg-IFN alfa-2b was administered at 1.5 µg/kg per week by subcutaneous injections on Days 1, 8, 15 and 21 |
| Liver samples from FNA | PROCEDURE | Liver samples were collected from Day 7 up to Day 10 by FNA at 3 of 5 specified postdose timepoints. |
| Vaniprevir 300 mg | DRUG | Vaniprevir capsules were administered orally, twice per day to achieve a final daily dose of 300 mg on Days 1 through 6; and a single dose of 300 mg, orally, on Day 7. |
| Liver samples from CNB | PROCEDURE | Liver samples were collected from Day 8 up to Day 10 by CNB at 1 of 3 specified postdose timepoints. |
| Vaniprevir 200 mg | DRUG | single dose administration of 200 mg oral tablet |
Inclusion criteria: * Japanese participant diagnosed with compensated CHC GT 1 * Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease * Has received and tolerated treatment with IFN-based therapy (IFN α, IFN β, or peg-IFN) wit...
Vaniprevir is an investigational small molecule being developed for the treatment of Hepatitis C, including chronic Hepatitis C. It is being studied in combination with pegylated-interferon and ribavirin in patients with Hepatitis C virus infection.
Vaniprevir is a small molecule that targets the Hepatitis C virus. It is being studied as a direct-acting antiviral agent for the treatment of Hepatitis C, including chronic infection.
Vaniprevir is being developed by Merck & Company, Inc., which is publicly traded under the ticker symbol MRK.
Vaniprevir is currently in Phase 1 clinical development. It has completed Phase 2 trials for Hepatitis C, but the most advanced ongoing development is Phase 1. It is not yet approved by the FDA and remains investigational.
Vaniprevir has been studied in several clinical trials, including NCT00704184, NCT00704405, NCT00880763, and NCT01010906. These trials evaluated its safety and efficacy in Hepatitis C patients, including treatment-experienced and Japanese populations, as well as its pharmacokinetics in hepatic insufficiency.