Clinical trial NCT00705432: Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)
Official title: A Phase 3, Safety and Efficacy Study of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-06-26
Enrollment: 1472
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study involves treatment with boceprevir or placebo in combination with PegIntron (PEG) + Ribavirin (RBV) (weight-based dosing \[WBD\]) in previously untreated adult participants with chronic hepatitis C (CHC) genotype 1. It is hypothesized that the addition of a third active anti- Hepatitis C Virus (anti-HCV) drug may lead to more rapid viral response than therapy with two drugs, and therefore, the addition of boceprevir to PegIntron plus ribavirin therapy after a 4-week lead-in period may allow for both increased rates of sustained virologic response (SVR) and shorter treatment durations (in some populations) than treatment with PegIntron plus ribavirin alone.

The study includes two separate cohorts, Cohort I (White participants) and Cohort II (Black participants). Participants from each cohort are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).

Detailed description: Participants from Cohort I and Cohort II are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).

1. Control arm, participants are treated with (PEG + RBV + placebo) for 44 weeks after the lead-in.
2. Experimental arm with Response Guided Therapy (RGT)

   In this experimental arm, participants are treated with all three drugs (PEG + RBV + boceprevir) for 24 weeks after the lead-in. At treatment week 28, those participants with undetectable Hepatitis C Virus - ribonucleic acid (HCV-RNA) from week 8 (up to treatment week 24), will be considered to complete treatment, and will enter follow-up. Participants with detectable for HCV-RNA at week 8 or later will receive an additional 20 weeks of therapy with PegIntron and Ribavirin (PEG + RBV + placebo).
3. Experimental arm, participants are treated with all three drugs (PEG + RBV + Ribavirin) for 44 weeks after the lead-in.

All participants were followed up to 72 weeks following randomization.

Eligibility criteria: Inclusion Criteria:

* Participant must have previously documented CHC genotype 1 infection.
* Participant must have a liver biopsy with histology consistent with CHC and no other etiology.
* Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC).
* Participant must be \>=18 years of age.
* Participant must weigh between 40 kg and 125 kg.
* Participant and participant's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations.
* Participants must be willing to give written informed consent.

Exclusion Criteria:

* Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
* Participants who received prior treatment for hepatitis C; other than herbal remedies, except those with known hepatotoxicity.
* Treatment with any investigational drug within 30 days of the randomization visit in this study.
* Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
* Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
* Diabetic and/or hypertensive participants with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality.
* Pre-existing psychiatric condition(s).
* Clinical diagnosis of substance abuse of the specified drugs within the specified timeframes.
* Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the study.
* Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). Participants under evaluation for malignancy are not eligible.
* Participants who are pregnant or nursing. Participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period.
* Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
* Participants who are part of the site personnel directly involved with this study.
* Participants who are family members of the investigational study staff.
* Participants who had life-threatening serious adverse event (SAE) during screening period.
* Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin \<12 g/dL for females and \<13 g/dL for males; Neutrophils \<1500/mm\^3 (blacks: \<1200/mm\^3); Platelets \<100,000/mm\^3; Direct bilirubin \>1.5 x upper limit of normal (ULN)
* Serum albumin \< lower limit of normal (LLN)
* Thyroid-stimulating hormone (TSH) \>1.2 x ULN or \<0.8 x LLN of laboratory, with certain exceptions.
* Serum creatinine \>ULN of the laboratory reference.
* Protocol-specified serum glucose concentrations.
* protocol-specified alpha fetoprotein levels.
* Prothrombin time/partial thromboplastin time (PT/PTT) values \>10% above laboratory reference range.
* Anti-nuclear antibodies (ANA) \>1:320.

Primary outcomes:
measure: Sustained Virologic Response (SVR) Rate
timeFrame: At Follow-up Week (FW) 24
Secondary outcomes:
measure: Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)
timeFrame: At FW 24
measure: Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.
timeFrame: At FW 12 and at 72 weeks after randomization
measure: Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)
timeFrame: At Treatment Week 2, 4, 8, 12, 16, or 20
measure: Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR
timeFrame: At Treatment Week 4, 8, 12, 16, 20
Other outcomes:
Locations:
Study officials:
References:
citation: Ferrante SA, Chhatwal J, Brass CA, El Khoury AC, Poordad F, Bronowicki JP, Elbasha EH. Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study. BMC Infect Dis. 2013 Apr 27;13:190. doi: 10.1186/1471-2334-13-190.
citation: Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS, Poynard T, Morgan TR, Molony C, Pedicone LD, Sings HL, Burroughs MH, Sniukiene V, Boparai N, Goteti VS, Brass CA, Albrecht JK, Bacon BR; SPRINT-2 and RESPOND-2 Investigators. Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology. 2012 Sep;143(3):608-618.e5. doi: 10.1053/j.gastro.2012.05.011. Epub 2012 May 21.
citation: Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1195-206. doi: 10.1056/NEJMoa1010494.