Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01945294 | Short Duration Versus Standard Response-Guided Therapy With Boceprevir Combined With PegIntron and Ribavirin in Previously Untreated Non-Cirrhotic Asian Participants With Chronic HCV Genotype 1 (MK-3034-107) | PHASE3 | COMPLETED | 257 | — | — | Oct 10, 2013 | Nov 4, 2015 | Jul 12, 2018 | - | — |
| NCT01390844 | Safety and Efficacy of Boceprevir in Asia Pacific Participants With Chronic Hepatitis C Genotype 1 (P07063) | PHASE3 | COMPLETED | 282 | — | — | Oct 21, 2011 | Jun 19, 2015 | Sep 11, 2018 | - | — |
| NCT01023035 | Boceprevir/Peginterferon/Ribavirin for Chronic Hepatitis C: Erythropoietin Use Versus Ribavirin Dose Reduction for Anemia (P06086 AM2) | PHASE3 | COMPLETED | 687 | — | — | Dec 7, 2009 | Oct 26, 2011 | Feb 8, 2021 | - | — |
| NCT00910624 | Boceprevir Treatment in Participants With Chronic Hepatitis C Genotype 1 Deemed Nonresponders to Peginterferon/Ribavirin (P05514) | PHASE3 | COMPLETED | 168 | — | — | Jun 22, 2009 | Dec 7, 2012 | Feb 8, 2021 | - | — |
| NCT00845065 | Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05685AM2)(COMPLETED) | PHASE3 | COMPLETED | 202 | — | — | Feb 1, 2009 | Oct 1, 2010 | Apr 7, 2017 | - | — |
| NCT00708500 | Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05101AM3)(COMPLETED) | PHASE3 | COMPLETED | 404 | — | — | Aug 1, 2008 | Apr 1, 2010 | Apr 7, 2017 | - | — |
SVR12 was declared when participants who had undetectable HCV RNA (HCV RNA \< Lower Limit of Quantification \[LLoQ\]) after the 12-week lead-in also had undetectable HCV RNA 12 weeks after completing their assigned BOC treatment regimen. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.
SVR is defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The last observation carried forward (LOCF) method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR.
SVR is defined as undetectable plasma HCV-RNA at FW24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The LOCF method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR.
SVR was defined as undetectable plasma Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week 24
SVR24 was defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week (FW) 24. SVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies.
AE= any untoward medical occurrence in a participant administered a pharmaceutical product/biologic (at any dose), whether or not considered related to the use of that product. Included the onset of new illness and the exacerbation of pre-existing conditions. Clinically significant laboratory abnormalities that required intervention/additional therapy, required a dose modification, or were associated with a clinical manifestation were considered AEs. SAE= any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, or was a congenital anomaly or birth defect.
SVR rate was the percentage of participants treated with at least one dose of study medication (PEG2a, Ribavirin, or Boceprevir/Placebo) who had achieved SVR. SVR was defined as undetectable Hepatitis C Virus-Ribonucleic Acid (HCV RNA).
SVR is defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at Follow-up Week 24. This outcome measure evaluates SVR after treatment with boceprevir and PEG2b plus RBV versus PEG2b plus RBV alone in participants with chronic hepatitis C (CHC) genotype 1 who failed prior treatment.
| Arm | Type | Description |
|---|---|---|
| Arm 1: 16-week Treatment Arm | EXPERIMENTAL | All screened and enrolled participants initially underwent a 12-week (4 weeks PR + 8 weeks BOC + PR) lead-in treatment period prior to randomization to Arms 1 or 2 (participants with undetectable HCV RNA) or allocation to Arm 3 (participants with detectable HCV RNA). After completing the 12-week lead-in, participants with undetectable HCV RNA were randomized to receive an additional 4 weeks of BOC + PR, for a total of 16 weeks of treatment. At Week 16, participants underwent 12 weeks of follow-up (participation complete at Week 28). |
| Arm 2: 28-week Treatment Arm | EXPERIMENTAL | All screened and enrolled participants initially underwent a 12-week (4 weeks PR + 8 weeks BOC + PR) lead-in treatment period prior to randomization to Arms 1 or 2 (participants with undetectable HCV RNA) or allocation to Arm 3 (participants with detectable HCV RNA). After completing the 12-week lead-in, participants with undetectable HCV RNA were randomized to receive an additional 16 weeks of BOC + PR, for a total of 28 weeks of treatment. At Week 28, participants underwent 12 weeks of follow-up (participation complete at Week 40). |
| Arm 3: 48-week Treatment Arm | EXPERIMENTAL | All screened and enrolled participants initially underwent a 12-week (4 weeks PR + 8 weeks BOC + PR) lead-in treatment period prior to randomization to Arms 1 or 2 (participants with undetectable HCV RNA) or allocation to Arm 3 (participants with detectable HCV RNA). After completing the 12-week lead-in, participants with detectable HCV RNA were allocated to receive an additional 24 weeks of BOC + PR and an additional 12 weeks of PR, for a total of 48 weeks of treatment. At Week 48, participants underwent 12 weeks of follow-up (participation complete at Week 60). |
| Boceprevir | EXPERIMENTAL | PEG + RBV for 4 weeks followed by BOC + PEG + RBV for 32 weeks. At the Treatment Week 36 visit, participants with undetectable HCV-RNA at Treatment Weeks 8 and 12 will proceed to 36 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 8 and undetectable HCV-RNA at Treatment Week 12 will continue on BOC + PEG + RBV until Treatment Week 36, receive placebo + PEG + RBV until Treatment Week 48, and then proceed to 24 weeks of post-treatment follow-up. Participants with any HCV-RNA result at Treatment Week 8 and detectable HCV-RNA at Treatment Week 12 will discontinue treatment and proceed to 24 weeks of post-treatment follow-up. |
| Control | ACTIVE_COMPARATOR | PEG + RBV for 4 weeks followed by BOC placebo + PEG + RBV for 44 weeks. Participants with undetectable HCV-RNA at Treatment Week 12 and at subsequent assays will continue on placebo + PEG + RBV through Treatment Week 48 and proceed to 24 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 12 may roll over to Cross-Over BOC treatment beginning with Treatment Week 14. |
| Treated/Not Randomized | EXPERIMENTAL | Participants received 4 weeks of PEG2b/RBV followed by 24 or 44 weeks of boceprevir plus PEG2b/RBV depending on Hepatitis C Virus RNA (HCV-RNA) levels. Participants continued with this treatment if their serum hemoglobin remained \>10 g/dL throughout the 28- or 48-week treatment period. |
| Ribavirin Dose Reduction | EXPERIMENTAL | After the initiation of treatment with 4 weeks with PEG2b/RBV followed by 24 or 44 weeks of boceprevir, participants who became anemic (serum hemoglobin = ≤10 g/dL) within the 28- or 48-week treatment period and who were randomized to the Ribavirin (RBV) Dose Reduction Arm received reduced doses of RBV for management of the anemia in combination with PEG2b and boceprevir therapies. |
| Erythropoietin Use | EXPERIMENTAL | After the initiation of treatment with 4 weeks with PEG2b/RBV followed by 24 or 44 weeks of boceprevir, participants who became anemic (serum hemoglobin = ≤10 g/dL) within the 28- or 48-week treatment period and who were randomized to the Erythropoietin Use Arm received erythropoietin for management of the anemia in addition to PEG2b/RBV and boceprevir therapies. |
| BOC + PEG/RBV | EXPERIMENTAL | Participants who enrolled within 2 weeks after the last dose of PEG/RBV in previous protocol received boceprevir (BOC) + peginterferon/ribavirin (PEG/RBV) for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who did not enroll within 2 weeks after the last dose of PEG/RBV in previous protocol received PEG/RBV for 4 weeks followed by BOC + PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up. |
| Arm 1 (Control Arm) | PLACEBO_COMPARATOR | Peginterferon alfa-2a (180 μg/week subcutaneously \[SC\]) plus ribavirin (1000 to 1200 mg/day orally \[PO\]) for 4 weeks followed by placebo (800 mg three times a day \[TID\] PO, using placebo matching SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up. |
| Arm 2 (Boceprevir Arm) | EXPERIMENTAL | Peginterferon alfa-2a (180 μg/week subcutaneously \[SC\]) plus ribavirin (1000 to 1200 mg/day orally \[PO\]) for 4 weeks followed by boceprevir (800 mg three times a day \[TID\] PO, using SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up. |
| Placebo+PEG2b+RBV, x 44 weeks | PLACEBO_COMPARATOR | Participants in Arm 1 (control) received pegylated interferon alfa 2b (PegIntron, PEG2b) + Ribavirin (RBV) (weight-based dosing \[WBD\]) for 4 weeks followed by boceprevir placebo + PEG2b + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up. |
| Boceprevir+PEG2b+RBV, Response Guided Therapy | EXPERIMENTAL | Participants in Arm 2 (experimental) were assigned either a 36-week or 48-week course of therapy based on their HCV-RNA status at Treatment Week 8. PEG2b + RBV (WBD) for 4 weeks followed by boceprevir + PEG2b + RBV (WBD) for 32 weeks, then: * 36-week regimen: Participants who have undetectable HCV-RNA at Treatment Week 8 discontinue treatment and enter 36 weeks of post treatment follow-up. * 48-week regimen: Participants who have detectable HCV-RNA at Treatment Week 8 are assigned an additional 12 weeks of therapy, followed by 24 weeks of post treatment follow-up. Placebo replaces boceprevir for the remaining 12 weeks of therapy, and this switch will occur in a blinded fashion. |
| Boceprevir+PEG2b+RBV, x 44 weeks | EXPERIMENTAL | Participants in Arm 3 (experimental) received PEG2b + RBV (WBD) for 4 weeks followed by boceprevir + PEG2b + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up. |
| Name | Type | Description |
|---|---|---|
| Boceprevir | DRUG | 800 mg three times daily orally |
| Peg-interferon alfa-2b | BIOLOGICAL | 1.5 mcg/kg weekly subcutaneously |
| Ribavirin | DRUG | 800-1400 mg twice-daily divided orally based on body weight |
| Boceprevir (BOC) | DRUG | 200 mg capsules, 800 mg three times daily by mouth |
| Placebo to boceprevir | DRUG | 200 mg placebo capsules, 800 mg three times daily by mouth |
| Peginterferon alfa-2b (PEG) | DRUG | 1.5 mcg/kg/week subcutaneously |
| Ribavirin (RBV) | DRUG | 200 mg capsules, weight-based dosing 800 to 1400 mg/day by mouth divided twice daily |
| Cross-Over Boceprevir Treatment | DRUG | At Treatment Week 14, participants in the Placebo group with detectable HCV-RNA at Treatment Week 12 have the option to add boceprevir 800 mg three times daily to the PEG + RBV regimen for up to 32 weeks. |
| Peginterferon alfa-2b (PEG2b) | DRUG | 1.5 µg/kg/week given subcutaneously (SC) |
| Erythropoietin | DRUG | Initial dose of 40,000 Units given subcutaneously (SC) once weekly (QW), with dose adjustment as necessary to achieve and maintain serum hemoglobin levels of 10-12 g/dL |
| Peginterferon alfa-2b (SCH 54031) | BIOLOGICAL | Peginterferon alfa-2b 1.5 µg/kg/week subcutaneously (SC) |
| Ribavirin (SCH 18908) | DRUG | Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day PO divided twice daily (BID). |
| Placebo | OTHER | 800 mg, using placebo matching SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks |
| Peginterferon alfa-2a | BIOLOGICAL | Peginterferon alfa-2a, pre-filled syringes, given 180 μg/week subcutaneously (SC) for 48 weeks |
| Boceprevir (SCH 503034) | DRUG | Boceprevir, 200 mg capsules, 800 mg TID PO |
| Pegylated interferon alfa-2b (SCH 54031) | BIOLOGICAL | PEG2b 1.5 μg/kg/week subcutaneously (SC) |
| Boceprevir placebo | DRUG | Boceprevir placebo, 200 mg capsules, 800 mg three times daily (TID) PO. |
Inclusion Criteria: * weigh ≥ 40 kg and ≤ 125 kg * have CHC genotype 1 infection * has had a liver biopsy or non-invasive liver fibrosis test that shows no evidence of cirrhosis and hepatocellular carcinoma * must agree that the participant and the participant's partner will each use acceptable met...