A Phase 2b Study of Daclatasvir in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 1 and 4 Infection
Overview
- Phase
- Phase 2
- Intervention
- peg-interferon alfa-2a
- Conditions
- Hepatitis C Virus
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 558
- Locations
- 36
- Primary Endpoint
- Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
To establish that at least 1 dose of daclatasvir combined with standard of care (pegylated interferon and ribavirin) is safe and well tolerated and demonstrates extended rapid virologic response rates at least 35% greater than those with placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients chronically infected with hepatitis C virus (HCV) genotype 1 or 4
- •HCV RNA viral load of ≥100,000 IU/mL
- •No previous exposure to interferon, pegIFNα, or RBV
- •Results of a liver biopsy demonstrating absence of cirrhosis obtained ≤24 months prior to randomization. Compensated cirrhotics with Hepatitis C virus genotype 1 infection are eligible, but will be capped at 10% of the randomized study population (biopsy can be from any time period prior to randomization)
- •Findings on ultrasound, computed tomography scan, or magnetic resonance imaging 12 months prior to randomization that do not demonstrate evidence of hepatocellular carcinoma
- •Body mass index of 18 to 35 kg/m\^2
Exclusion Criteria
- •Positive for hepatitis B or HIV-1/HIV-2 antibody at screening
- •Evidence of a medical condition associated with chronic liver disease other than HCV
- •Evidence of decompensated cirrhosis based on radiologic criteria or biopsy
Arms & Interventions
Placebo plus peg-interferon alfa-2a and ribavirin
Intervention: peg-interferon alfa-2a
Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
Intervention: Daclatasvir
Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
Intervention: peg-interferon alfa-2a
Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
Intervention: ribavirin
Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
Intervention: Daclatasvir
Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
Intervention: peg-interferon alfa-2a
Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
Intervention: ribavirin
Placebo plus peg-interferon alfa-2a and ribavirin
Intervention: Placebo
Placebo plus peg-interferon alfa-2a and ribavirin
Intervention: ribavirin
Outcomes
Primary Outcomes
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died
Time Frame: From start of study treatment (day 1) up to follow-up Week 48
SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR)
Time Frame: Weeks 4 and 12
eRVR was defined as HCV RNA \<lower limit of quantitation and target not detected at both Weeks 4 and 12 on treatment.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24)
Time Frame: Follow-up Week 24
SVR24 was defined as HCV \<lower limit of quantitation (LLOQ) and target not detected (TND) at follow-up Week 24. The LLOQ was 25 IU/mL, and \<LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Secondary Outcomes
- Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR)(Week 4)
- Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR)(Week 12)
- Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12)(Follow-up Week 12)
- Percentage of Resistant Variants Associated With Virologic Failure(Follow-up Week 48)