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

Study Description

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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 Design

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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
Actual Primary Completion Date :	September 2013
Actual Study Completion Date :	December 2013

Arms and Interventions

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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®

Outcome Measures

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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 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

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Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

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Additional Information:

BMS Clinical Trial Information 

BMS clinical trial educational resource 

Investigator Inquiry form 

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jensen D, Sherman KE, Hézode C, Pol S, Zeuzem S, de Ledinghen V, Tran A, Elkhashab M, Younes ZH, Kugelmas M, Mauss S, Everson G, Luketic V, Vierling J, Serfaty L, Brunetto M, Heo J, Bernstein D, McPhee F, Hennicken D, Mendez P, Hughes E, Noviello S; HALLMARK-QUAD Study Team. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015 Jul;63(1):30-7. doi: 10.1016/j.jhep.2015.02.018. Epub 2015 Feb 19.

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01573351 History of Changes
Other Study ID Numbers:	AI447-029; 2011-005422-21 ( EudraCT Number )
First Posted:	April 9, 2012
Last Update Posted:	October 9, 2015
Last Verified:	September 2015

Additional relevant MeSH terms:

Hepatitis; Hepatitis C; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Interferons; Ribavirin	Interferon-alpha; Peginterferon alfa-2a; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs