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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01573351
Recruitment Status : Completed
First Posted : April 9, 2012
Last Update Posted : October 9, 2015
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatitis C Virus Drug: Asunaprevir Drug: Daclatasvir Drug: Peg-interferon Alfa-2a Drug: Ribavirin Phase 3

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 398 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label Study With Asunaprevir and Daclatasvir Plus Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) (P/R) (QUAD) for Subjects Who Are Null or Partial Responders to Peginterferon Alfa 2a or 2b Plus Ribavirin With Chronic Hepatitis C Genotypes 1 or 4 Infection
Study Start Date : May 2012
Primary Completion Date : September 2013
Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin

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

Drug: Asunaprevir
Other Name: BMS-650032
Drug: Daclatasvir
Other Name: BMS-790052
Drug: Peg-interferon Alfa-2a
Other Name: Pegasys®
Drug: Ribavirin
Other Name: Copegus®

Primary Outcome Measures :
  1. Proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1 [ Time Frame: At 12 weeks post-treatment ]

Secondary Outcome Measures :
  1. On-treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) through the end of treatment [ Time Frame: Through the end of treatment (maximum up to 24 weeks) plus 7 days ]
  2. Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene [ Time Frame: At post-treatment Week 12 ]
  3. Proportion of subjects with HCV RNA undetectable [ Time Frame: Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [Extended rapid virologic response (eRVR)], end of treatment (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24 ]
  4. Proportion of subjects with HCV RNA < LOQ [ Time Frame: Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12, end of treatment (up to 24 weeks), post-treatment Week 24 (SVR24) ]
  5. Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects [ Time Frame: Post-treatment Week 12 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01573351

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Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb Identifier: NCT01573351     History of Changes
Other Study ID Numbers: AI447-029
2011-005422-21 ( EudraCT Number )
First Posted: April 9, 2012    Key Record Dates
Last Update Posted: October 9, 2015
Last Verified: September 2015

Additional relevant MeSH terms:
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Peginterferon alfa-2a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs