Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)

NCT00705432 | Completed Phase 3 Results DMC

• 2 other identifiers: P05216EUDRACT # 2007-005508-42
• Study Type: interventional
• Target: 1,472
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• Sustained Virologic Response (SVR) Rate

  Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate is the percent of participants achieving SVR. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL. If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have SVR.

  At Follow-up Week (FW) 24

Secondary Outcomes (4)

• Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)

  At FW 24

• Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.

  At FW 12 and at 72 weeks after randomization

• Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)

  At Treatment Week 2, 4, 8, 12, 16, or 20

• Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR

  At Treatment Week 4, 8, 12, 16, 20

Study Arms (3)

1. Placebo + PEG + RBV

PLACEBO COMPARATOR

PegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing \[WBD\]) for 4 weeks (lead in treatment) followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.

Biological: Peginterferon alfa-2b (PEG); Drug: Ribavirin (RBV); Drug: Placebo

2. Boceprevir + PEG + RBV - 24 Weeks (RGT)

EXPERIMENTAL

PEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks. Participants were offered a response guided therapy (RGT) at treatment week 28. * At the Treatment Week 28 visit, participants whose HCV-RNA was undetectable from Treatment Weeks 8 to Treatment Week 24, will proceed to the 44-week follow-up. * At the Treatment Week 28 visit, participants with detectable HCV-RNA at Treatment Week 8 or at any subsequent assays will continue on therapy with placebo + PEG 1.5 μg/kg + RBV (WBD) for an additional 20 weeks, to complete a total of 48 weeks on treatment with 24 weeks post-treatment follow-up.

Biological: Peginterferon alfa-2b (PEG); Drug: Ribavirin (RBV); Drug: Boceprevir

3. Boceprevir + PEG + RBV - 44 Weeks

EXPERIMENTAL

PEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.

Biological: Peginterferon alfa-2b (PEG); Drug: Ribavirin (RBV); Drug: Boceprevir

Interventions

Peginterferon alfa-2b (PEG) BIOLOGICAL

Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)

Also known as: PegIntron, PEG, SCH 54031

1. Placebo + PEG + RBV; 2. Boceprevir + PEG + RBV - 24 Weeks (RGT); 3. Boceprevir + PEG + RBV - 44 Weeks

Ribavirin (RBV) DRUG

Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day administered orally, divided twice daily (BID).

Also known as: Rebetol, RBV, SCH 18908

1. Placebo + PEG + RBV; 2. Boceprevir + PEG + RBV - 24 Weeks (RGT); 3. Boceprevir + PEG + RBV - 44 Weeks

Placebo DRUG

Placebo to boceprevir, 800 mg (4 x 200mg capsules) administered orally three times a day (TID).

1. Placebo + PEG + RBV

Boceprevir DRUG

Boceprevir, 800 mg (4 x 200 mg capsules) administered orally TID.

Also known as: SCH 503034, Victrelis

2. Boceprevir + PEG + RBV - 24 Weeks (RGT); 3. Boceprevir + PEG + RBV - 44 Weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• 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.

  PMID: 23621902 DERIVED

• 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.

  PMID: 22626609 DERIVED

• 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.

  PMID: 21449783 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2b; Ribavirin; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2008
• First Posted: June 26, 2008
• Study Start: August 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: April 7, 2017
• Results First Posted: June 14, 2011

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share