Clinical trial NCT00708500
Conditions: Hepatitis C, Chronic
Keywords: Treatment failure
Sponsor: Merck Sharp & Dohme LLC
Start date: 2008-08-01; Completion date: 2010-04-01
Enrollment: 404 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study involves treatment with boceprevir or placebo in combination with pegylated interferon alfa-2b (PegIntron, PEG2b) + Ribavirin (RBV) (weight-based dosing \[WBD\]) in adult subjects with chronic hepatitis C (CHC) genotype 1 who demonstrated interferon responsiveness (a decrease in hepatitis C virus RNA \[HCV-RNA\] viral load \>=2 log10 by Week 12 or undetectable HCV-RNA at end of treatment) but who failed to achieve sustained virologic response (SVR) on prior treatment with any combination therapy of peginterferon alpha and RBV. This trial includes three arms, one control arm (PEG2b + RBV for 48 weeks) and two experimental arms (PEG2b + RBV + boceprevir). One of the experimental arms, Arm 3, consists of treatment with all three drugs for 44 weeks after the lead-in. The other experimental arm, Arm 2, consists of all three drugs for 32 weeks after the lead-in. Participants in Arm 2 who were undetectable for HCV-RNA at Treatment Week 8 will complete treatment at that point. Those who were not undetectable for HCV-RNA at Treatment Week 8 will receive an additional 12 weeks of PEG2b + RBV + boceprevir placebo. It is hypothesized that the addition of a third active anti-HCV drug may lead to more rapid viral response than therapy with two drugs, and therefore, the addition of boceprevir to PEG2b plus RBV therapy after a 4-week lead-in period may allow for both increased rates of SVR and shorter treatment durations (in some populations) than treatment with peginterferon plus RBV alone.

Detailed description:

Arms: arm 1: 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. arm 2: 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. arm 3: 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.
Interventions: intervention 1: Boceprevir (SCH 503034) intervention 2: Pegylated interferon alfa-2b (SCH 54031) intervention 3: Ribavirin (SCH 18908) intervention 4: Boceprevir placebo
Intervention descriptions: intervention 1: Boceprevir, 200 mg capsules, 800 mg TID PO intervention 2: PEG2b 1.5 μg/kg/week subcutaneously (SC) intervention 3: Ribavirin WBD 600 mg/day to 1400 mg/day by mouth (PO) divided twice daily (BID). intervention 4: Boceprevir placebo, 200 mg capsules, 800 mg three times daily (TID) PO.

Protocol documents: