Study in Genotype 2 or 3 Patients With Chronic Hepatitis Virus Infection
- Conditions
- Hepatitis C Virus
- Interventions
- Registration Number
- NCT01257204
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
To identify a shorter duration of antiviral therapy (12 or 16 weeks) for the combination of daclatasvir with pegylated interferon alfa-2a and ribavirin.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 196
- Participants chronically infected with hepatitis C virus (HCV) genotype 2 or 3
- No previous exposure to an interferon formulation (ie, interferon alfa, pegylated interferon alfa-2a ) or ribavirin
- Body mass index (BMI) of 18 to 35 kg/m^2, inclusive. BMI=weight (kg)/height (m)^2
- Males and females, 18 - 70 years of age
Key
- Liver transplant recipients
- Documented or suspected hepatocellular carcinoma
- Evidence of decompensated cirrhosis
- History of chronic hepatitis B virus (HBV). Patients with resolved HBV infection may participate
- Current or known history of cancer
- Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug
- Inability to tolerate oral medication
- Poor venous access
- Severe psychiatric disease
- History of chronic pulmonary disease
- History of cardiomyopathy, coronary artery disease (including angina), interventive procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia,, or other clinically significant cardiac disease
- History of or current electrocardiogram findings indicative of cardiovascular instability
- Preexisting ophthalmologic disorders considered clinically significant on eye
- History of uncontrolled diabetes mellitus
- Any known contraindication to pegylated interferon alfa-2a or ribavirin not otherwise specified.
- Positive hepatitis B virus surface antigen, HIV-1 or HIV-2 Ab
- Prior exposure to any HCV direct antiviral agent (eg, HCV protease, polymerase, previous nonstructural protein 5A inhibitors)
- Exposure to any investigational drug or placebo
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Placebo Placebo + Pegylated interferon alfa-2a + Ribavirin Control Pegylated interferon alfa-2a Placebo + Pegylated interferon alfa-2a + Ribavirin 12 Week Cohort Daclatasvir Daclatasvir + Pegylated interferon alfa-2a + Ribavirin Control Ribavirin Placebo + Pegylated interferon alfa-2a + Ribavirin 12 Week Cohort Pegylated interferon alfa-2a Daclatasvir + Pegylated interferon alfa-2a + Ribavirin 12 Week Cohort Ribavirin Daclatasvir + Pegylated interferon alfa-2a + Ribavirin 16 Week Cohort Daclatasvir Daclatasvir + Pegylated interferon alfa-2a + Ribavirin 16 Week Cohort Pegylated interferon alfa-2a Daclatasvir + Pegylated interferon alfa-2a + Ribavirin 16 Week Cohort Ribavirin Daclatasvir + Pegylated interferon alfa-2a + Ribavirin
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 Follow-up Week 24 SVR24 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], 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.
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 Follow-up Week 24 SVR24 was defined as undetectable HCV RNA (HCV RNA \<lower limit of quantitation \[LLOQ\], 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 Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 Week 4 RVR was defined as undetectable HCV 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.
Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 Week 4 RVR was defined as undetectable HCV 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.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period Baseline (Day 1) up to 24 weeks (treatment period) AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has a causal relationship with treatment. 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. Mild (Grade 1): awareness of event but easily tolerated; Moderate (Grade 2): discomfort enough to cause some interference with usual activity; Severe (Grade 3): inability to carry out usual activity; Very severe (Grade 4): debilitating, significantly incapacitates participant despite symptomatic therapy. Only Grade 2-4 treatment-related AEs were reported.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period From end of treatment period up to Week 48 (follow-up period) AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has a causal relationship with treatment. 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 Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 Week 12 cEVR was defined as undetectable HCV 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.
Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 Week 12 cEVR was defined as undetectable HCV 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.
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 Follow-up Week 12 SVR12 was defined as undetectable HCV 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.
Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 Follow-up Week 12 SVR12 was defined as undetectable HCV 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.
Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 Baseline up to Week 48 Virologic failure was defined as:
1. Virologic breakthrough: confirmed \>1 log10 increase in 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 or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation)
5. 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.Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 Baseline up to Week 48 Virologic failure was defined as:
1. Virologic breakthrough: confirmed \>1 log10 increase in 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 or \<LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation)
5. 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.
Trial Locations
- Locations (5)
California Liver Institute
🇺🇸Los Angeles, California, United States
Local Institution
🇮🇹Viale Del Policlinico, 155, Italy
Options Health Research, Llc
🇺🇸Tulsa, Oklahoma, United States
Digestive Disease Associates, P.A.
🇺🇸Baltimore, Maryland, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States