Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Hepatitis C Virus

Treatments: Drug: Asunaprevir (ASV); Drug: Ribavirin (RBV); Drug: Pegylated-interferon alfa 2a (PegIFN); Drug: Daclatasvir (DCV)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01581203

AI447-028

2011-005446-35 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to estimate efficacy, as determined by the proportion of subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who are treatment-naive.

Full description

Allocation: Treatment naive cohort: Randomized Controlled Trial, Null/partial responder and intolerant/ineligible cohorts: N/A (Single arm study)

Masking: Treatment naive cohort: Double Blind, Null/partial responder and intolerant/ineligible cohorts: Open

Intervention Model: Treatment naive cohort: Parallel, Null/partial responder and intolerant/ineligible cohorts: Single group

Enrollment: 748 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Males and females, ≥ 18 years of age
• HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin, classified as previous null or partial responders based on previous therapy, OR intolerant or ineligible to P/R due to neutropenia, anemia, depression or thrombocytopenia with fibrosis/cirrhosis, OR treatment naive
• HCV RNA ≥ 10,000 IU/mL
• Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg)
• Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population)

Exclusion Criteria:

• Prior treatment of HCV with HCV direct acting antiviral (DAA)
• Evidence of a medical condition contributing to chronic liver disease other than HCV
• Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
• Diagnosed or suspected hepatocellular carcinoma or other malignancies
• Uncontrolled diabetes or hypertension

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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748 participants in 4 patient groups

Arm 1: Null or Partial Responder to P/R (ASV + DCV)

Experimental group

Description:

Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

Treatment:

Drug: Daclatasvir (DCV)

Drug: Asunaprevir (ASV)

Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV)

Experimental group

Description:

Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

Treatment:

Drug: Daclatasvir (DCV)

Drug: Asunaprevir (ASV)

Arm 3: Treatment naive (ASV + DCV)

Experimental group

Description:

\[Subjects will receive ASV + DCV for 24 weeks\] followed by ASV + DCV for 24 weeks in protocol AI444026\] Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks

Treatment:

Drug: Daclatasvir (DCV)

Drug: Pegylated-interferon alfa 2a (PegIFN)

Drug: Ribavirin (RBV)

Drug: Asunaprevir (ASV)

Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week

Experimental group

Description:

Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks

Treatment:

Drug: Daclatasvir (DCV)

Drug: Pegylated-interferon alfa 2a (PegIFN)

Drug: Ribavirin (RBV)

Drug: Asunaprevir (ASV)