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: May 5, 2014
Last verified: May 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 Drug: Asunaprevir
Capsule, Oral, 100 mg, Twice daily, 24 weeks
Other Name: BMS-650032
Drug: Daclatasvir
Tablet, Oral, 60 mg, Once daily, 24 weeks
Other Name: BMS-790052
Drug: Peg-interferon Alfa-2a
Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks
Other Name: Pegasys®
Drug: Ribavirin
Tablet, Oral, 1000 mg/1200 mg (depending on subject weight), Twice daily, 24 weeks
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 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
  • Confirmed Alanine aminotransferase (ALT) ≥ 5x Upper limit of normal (ULN)
  • Confirmed Albumin < 3.5 g/dL (35 g/L)
  • Alpha Fetoprotein (AFP) > 100 ng/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)
  • Confirmed 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

  Hide Study Locations
Locations
United States, Alabama
Alabama Liver & Digestive Specialists (Alds)
Montgomery, Alabama, United States, 36116
United States, California
Scripps Clinic
La Jolla, California, United States, 92037
Scpmg/ Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, United States, 90027
United States, Colorado
University Of Colorado Denver And Hospital
Aurora, Colorado, United States, 80045
South Denver Gastroenterology, Pc
Englewood, Colorado, United States, 80113
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
University Of Miami Schiff Center For Liver Diseases
Miami, Florida, United States, 33136
United States, Illinois
University Of Chicago Medical Center
Chicago, Illinois, United States, 60637-1432
United States, New York
North Shore University Hospital
Manhasset, New York, United States, 11030
United States, North Carolina
University Of North Carolina At Chapel Hill School Of Med
Chapel Hill, North Carolina, United States, 27599-7584
United States, Ohio
University Of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Oklahoma
Options Health Research, Llc
Tulsa, Oklahoma, United States, 74104
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Gastro One
Germantown, Tennessee, United States, 38138
United States, Texas
Baylor College Of Medicine
Houston, Texas, United States, 77030
Texas Liver Institute
San Antonio, Texas, United States, 78215
United States, Virginia
Mcguire Dvamc
Richmond, Virginia, United States, 23249
United States, Wisconsin
Dean Clinic
Madison, Wisconsin, United States, 53715
Argentina
Local Institution
Ciudad De Buenos Aires, Buenos Aires, Argentina, C1121ABE
Local Institution
Mar Del Plata, Buenos Aires, Argentina, 7600
Local Institution
Prov. Buenos Aires, Buenos Aires, Argentina, 1629
Canada, Alberta
Local Institution
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Local Institution
Vancouver, British Columbia, Canada, V6Z 2K5
Local Institution
Victoria, British Columbia, Canada, V8V 3P9
Canada, Ontario
Local Institution
Toronto, Ontario, Canada, M6H 3M1
Canada, Quebec
Local Institution
Montreal, Quebec, Canada, H2L 4P9
Denmark
Local Institution
Aalborg, Denmark, 9100
Local Institution
Hvidovre, Denmark, 2650
Local Institution
Odense, Denmark, 5000
France
Local Institution
Creteil, France, 94000
Local Institution
Montpellier Cedex 5, France, 34295
Local Institution
Nice Cedex 03, France, 06202
Local Institution
Paris Cedex 12, France, 75571
Local Institution
Paris Cedex 14, France, 75679
Local Institution
Pessac, France, 33604
Germany
Local Institution
Berlin, Germany, 13353
Local Institution
Duesseldorf, Germany, 40237
Local Institution
Frankfurt, Germany, 60590
Local Institution
Freiburg, Germany, 79106
Local Institution
Hamburg, Germany, 20246
Local Institution
Heidelberg, Germany, 69120
Local Institution
Tuebingen, Germany, 72076
Italy
Local Institution
Brescia, Italy, 25123
Local Institution
Cisanello (pisa), Italy, 56124
Local Institution
Milano, Italy, 20122
Local Institution
Palermo, Italy, 90127
Korea, Republic of
Local Institution
Bucheon-si, Korea, Republic of, 420-767
Local Institution
Busan, Korea, Republic of, 602-739
Local Institution
Busan, Korea, Republic of, 602-715
Local Institution
Busan, Korea, Republic of, 614-735
Local Institution
Daegu, Korea, Republic of, 700-721
Local Institution
Gyeongsangnam-do, Korea, Republic of, 626-770
Local Institution
Incheon, Korea, Republic of, 400-711
Local Institution
Incheon, Korea, Republic of, 403-720
Local Institution
Seoul, Korea, Republic of, 135-710
Local Institution
Seoul, Korea, Republic of, 120-752
Mexico
Local Institution
Mexico, Distrito Federal, Mexico, 03720
Local Institution
Mexico City, Estado De Mexico, Mexico, 06700
Netherlands
Local Institution
Amsterdam, Netherlands, 1105 AZ
Local Institution
Rotterdam, Netherlands, 3015 CE
Russian Federation
Local Institution
Moscow, Russian Federation, 127015
Local Institution
Moscow, Russian Federation, 117593
Local Institution
Saint-Petersburg, Russian Federation, 194044
Local Institution
Stavropol, Russian Federation, 355000
Local Institution
Tyumen, Russian Federation, 625026
Spain
Local Institution
Alcorcon, Spain, 28922
Local Institution
Barcelona, Spain, 08916
Local Institution
Madrid, Spain, 28029
Local Institution
Sevilla, Spain, 41014
Sweden
Local Institution
Gvteborg, Sweden, SE-41685
Local Institution
Stockholm, Sweden, 141 86
Switzerland
Local Institution
Bern, Switzerland, 3010
Local Institution
Lausanne, Switzerland, 1011
Taiwan
Local Institution
Chia-Yi, Taiwan, 600
Local Institution
Kaohsiung, Taiwan, 807
Local Institution
Taichung, Taiwan, 40705
Local Institution
Taipei, Taiwan, 11217
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: May 5, 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
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014