Study of Daclatasvir (BMS-790052) Add-on to Standard of Care in Treatment- naïve Patients
- Conditions
- Hepatitis C Virus
- Interventions
- Registration Number
- NCT01125189
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 558
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo plus peg-interferon alfa-2a and ribavirin Placebo - Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg) peg-interferon alfa-2a - Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg) ribavirin - Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg) Daclatasvir - Placebo plus peg-interferon alfa-2a and ribavirin peg-interferon alfa-2a - Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg) Daclatasvir - Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg) peg-interferon alfa-2a - Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg) ribavirin - Placebo plus peg-interferon alfa-2a and ribavirin ribavirin -
- Primary Outcome Measures
Name Time Method Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died 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) 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) 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 Outcome Measures
Name Time Method Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR) Week 4 RVR was defined as undetectable RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 4. 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. N=Number of participants analyzed for this outcome.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR) Week 12 cEVR was defined as undetectable RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at Week 12. 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. N=Number of participants analyzed for this outcome.
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12) Follow-up Week 12 SVR12 was defined as undetectable RNA (HCV RNA \< lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. 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. N=Number of participants analyzed for this outcome.
Percentage of Resistant Variants Associated With Virologic Failure Follow-up Week 48 Virologic failure was defined as:
1. Virologic breakthrough: confirmed \>1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA \<LLOQ, target not detected (TND) while on treatment
2. \<1 log10 decrease in HCV RNA from baseline at Week 4 of treatment
3. Failure to achieve early virologic response: \<2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment
4. HCV RNA \< LLOQ, TD or ≥ LLOQ at Week 12 and ≥ LLOQ at Week 24
5. HCV RNA ≥LLOQ or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation)
6. Relapse, defined as HCV RNA ≥LLOQ or \<LLOQ, TD during follow-up, after HCV RNA \< LLOQ, TND at EOT.
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. N=Number of participants analyzed for this outcome.
Trial Locations
- Locations (36)
University Of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Johns Hopkins University
🇺🇸Lutherville, Maryland, United States
Cli
🇺🇸Los Angeles, California, United States
Alabama Liver & Digestive Specialists (Alds)
🇺🇸Montgomery, Alabama, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
University Of Miami
🇺🇸Miami, Florida, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Digestive Disease Associates, P.A.
🇺🇸Baltimore, Maryland, United States
Claudia T. Martorell, Md, Llc
🇺🇸Springfield, Massachusetts, United States
James Sungsik Park, M.D. C.N.S.C.
🇺🇸Great Neck, New York, United States
Carolinas Center For Liver Disease
🇺🇸Statesville, North Carolina, United States
Upper Delaware Valley Infectious Diseases, Pc
🇺🇸Monticello, New York, United States
Healthcare Research Consultants
🇺🇸Tulsa, Oklahoma, United States
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
North Texas Research Institute
🇺🇸Arlington, Texas, United States
St. Luke'S Episcopal Hospital - Baylor College Of Medicine
🇺🇸Houston, Texas, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States
Metropolitan Research
🇺🇸Fairfax, Virginia, United States
Dean Clinic
🇺🇸Madison, Wisconsin, United States
Local Institution
🇸🇪Stockholm, Sweden
Local institution
🇨🇦Toronto, Ontario, Canada
Local Instituition
🇫🇷Paris Cedex 12, France
Options Health Research, Llc
🇺🇸Tulsa, Oklahoma, United States
James J Peters Vamc
🇺🇸Bronx, New York, United States
Desta Digestive Disease Medical Center
🇺🇸San Diego, California, United States
University Of California, San Francisco/Sf General Hospital
🇺🇸San Francisco, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Kaiser Permanente Medical Center
🇺🇸San Francisco, California, United States
Transplant Center And Hepatology Clinic, B-154
🇺🇸Aurora, Colorado, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Nashville Medical Research Institute
🇺🇸Nashville, Tennessee, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
University Of North Carolina At Chapel Hill School Of Med
🇺🇸Chapel Hill, North Carolina, United States
University Of Florida Hepatology
🇺🇸Gainesville, Florida, United States