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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01573351
First received: April 5, 2012
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Hepatitis C Virus
Drug: Asunaprevir
Drug: Daclatasvir
Drug: Peg-interferon Alfa-2a
Drug: Ribavirin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]

Enrollment: 398
Study Start Date: May 2012
Study Completion Date: December 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01573351

  Show 79 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01573351     History of Changes
Other Study ID Numbers: AI447-029, 2011-005422-21
Study First Received: April 5, 2012
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration
Korea: Food and Drug Administration
Taiwan: Department of Health
Taiwan: National Bureau of Controlled Drugs
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
Brazil: Ministry of Health
Canada: Health Canada
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: FSI Scientific Center of Expertise of Medical Application
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency of Medicines
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
Sweden: Medical Products Agency
Sweden: The National Board of Health and Welfare
Sweden: Swedish Data Inspection Board
Sweden: Swedish National Council on Medical Ethics
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014