Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials)

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Hepatitis C Virus

Treatments: Drug: Daclatasvir; Drug: Asunaprevir; Drug: Ribavirin; Drug: Peg-interferon Alfa-2a

Study type: Interventional

Funder types: Industry

Identifiers

NCT01573351

2011-005422-21 (EudraCT Number)

AI447-029

Details and patient eligibility

About

The purpose of this study is to assess 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.

Full description

• ASV = Asunaprevir (BMS-650032)
• DCV = Daclatasvir (BMS-790052)
• Peg = Peg-interferon Alfa-2a (PegIFN)
• Rib = Ribavirin (RBV)

Enrollment: 398 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females, ≥ 18 years of age
• HCV Genotype 1 or 4 who previously failed treatment with Peginterferon alfa-2a or peginterferon alfa-2b and Ribavirin (P/R), classified as previous null and partial responders based on previous therapy
• 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
• Total bilirubin ≥ 34 μmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease
• Alanine aminotransferase (ALT) ≥ 5x Upper limit of normal (ULN)
• Albumin < 3.5 g/dL (35 g/L)
• Alpha Fetoprotein (AFP) > 100 ng/mL (>82.6 IU/mL) or ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of Hepatocellular carcinoma (HCC) are excluded
• Absolute neutrophil count (ANC) < 1.5 x 1000,000,000 cells/L (< 1.2 x 1000,000,000 cells/L for Black/African-Americans)
• Platelets < 90 x 1000,000,000 cells/L
• Hemoglobin < 12 g/dL for females or < 13 g/dL for males
• Any criteria that would exclude the subject from receiving P/R

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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398 participants in 1 patient group

QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin

Experimental group

Description:

Asunaprevir: Capsule, Oral, 100 mg, Twice daily, 24 weeks Daclatasvir: Tablet, Oral, 60 mg, Once daily, 24 weeks Peg-interferon Alfa-2a: Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks Ribavirin: Tablet, Oral, 1000 mg/1200 mg (total daily dose), 24 weeks

Treatment:

Drug: Peg-interferon Alfa-2a

Drug: Ribavirin

Drug: Asunaprevir

Drug: Daclatasvir