Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus

A Phase 3, Open Label Study of Safety and Efficacy With BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirin in Previously Untreated HCV Patients Coinfected With Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)

The purpose of this open label study is to evaluate the safety and efficacy of daclatasvir plus pegylated interferon-alfa 2a and ribavirin in untreated hepatitis C virus in patients coinfected with HIV

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Genotype 1
• Intervention / Treatment: Drug: Daclatasvir; Drug: Ribavirin; Drug: PEG-Interferon alfa 2a

• Study Type: Interventional
• Enrollment (Actual): 549
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1181
    • Local Institution
  • Buenos Aires, Argentina, C1181
    • Local Institution
  • Cordoba, Argentina, 5000
    • Local Institution
  • Buenos Aires
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1121ABE
      • Local Institution
  • Santa Fe
    • Prov De Santa Fe, Santa Fe, Argentina, 2000
      • Local Institution
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Local Institution
    • Darlinghurst Nsw, New South Wales, Australia, 2010
      • Local Institution
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution
    • Parkville, Victoria, Australia, 3050
      • Local Institution
• Belgium
  • Antwerpen, Belgium, 2000
    • Local Institution
  • Brussels, Belgium, 1070
    • Local Institution
  • Brussels, Belgium, B-1000
    • Local Institution
• Brazil
  • Rio De Janeiro, Brazil, 20270
    • Local Institution
  • Rio De Janeiro, Brazil, 21040
    • Local Institution
  • Sao Paulo, Brazil, 04035
    • Local Institution
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035
      • Local Institution
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Local Institution
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Local Institution
    • Victoria, British Columbia, Canada, V8V 3P9
      • Local Institution
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution
    • Torono, Ontario, Canada, M5G 2N2
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Local Institution
    • Montreal, Quebec, Canada, H3A 1T1
      • Local Institution
    • Montreal, Quebec, Canada, H2L 5B1
      • Local Institution
• France
  • Marseille Cedex 09, France, 13274
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Institution
  • Paris, France, 75013
    • Local Institution
  • Paris, France, 75014
    • Local Institution
  • Paris, France, 75018
    • Local Institution
  • Paris, France, 75571
    • Local Institution
  • Paris Cedex 10, France, 75475
    • Local Institution
  • Pessac Cedex, France, 33604
    • Local Institution
• Germany
  • Berlin, Germany, 13353
    • Local Institution
  • Bonn, Germany, 53105
    • Local Institution
  • Frankfurt, Germany, 60590
    • Local Institution
  • Frankfurt Am Main, Germany, 60311
    • Local Institution
  • Hamburg, Germany, 20146
    • Local Institution
• Italy
  • Brescia, Italy, 25123
    • Local Institution
  • Milano, Italy, 20127
    • Local Institution
  • Milano, Italy, 20162
    • Local Institution
  • Modena, Italy, 41100
    • Local Institution
  • Torino, Italy, 10149
    • Local Institution
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion De Investigacion de Diego
  • San Juan, Puerto Rico, 00935
    • University of Puerto Rico School of Medicine
• Russian Federation
  • Kaluga, Russian Federation, 248023
    • Local Institution
  • Lipetsk, Russian Federation, 398043
    • Local Institution
  • Moscow, Russian Federation, 111123
    • Local Institution
  • Nizhniy Novgorod, Russian Federation, 603005
    • Local Institution
  • Saratov, Russian Federation, 410009
    • Local Institution
  • St. Petersburg, Russian Federation, 191167
    • Local Institution
  • St. Petersburg, Russian Federation, 196645
    • Local Institution
  • St.petersburg, Russian Federation, 190103
    • Local Institution
  • Volgograd, Russian Federation, 400040
    • Local Institution
• Spain
  • Barcelona, Spain, 08003
    • Local Institution
  • Cordoba, Spain, 14004
    • Local Institution
  • Madrid, Spain, 28041
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
  • Sevilla, Spain, 41014
    • Local Institution
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Local Institution
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SW10 9NH
      • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Los Angeles, California, United States, 90027
      • Southern California Permanente Medical Group
    • Palm Springs, California, United States, 92262
      • Desert Medical Group Inc.
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center
    • San Francisco, California, United States, 94110
      • San Francisco Gen Hosp
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • Saint Michael's Medical Center
  • New York
    • Bronx, New York, United States, 10468
      • James J Peters VAMC
    • Monticello, New York, United States, 12701
      • Upper Delaware Valley Infectious Diseases, Pc
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28204
      • Morehead Medical Plaza
  • Texas
    • Dallas, Texas, United States, 75235
      • Amelia Court Hiv Research Clinic
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Key Inclusion Criteria:

• Males and females, 18 to 70 years of age
• Hepatitis C virus (HCV) genotype 1a or 1b
• HCV-treatment naive
• HCV RNA >10,000 IU/mL at screening
• HIV-1 infection (approximately 250 patients receiving highly active antiretroviral therapy [HAART], up to 50 patients not receiving HAART)
• For patients receiving HAART, HIV RNA must be below <40 copies/mL at screening and must be <400 copies/ml for at least 6 months prior to screening

Key Exclusion Criteria:

• Patients receiving HAART who first initiated antiretroviral therapy within the last 6 months of Day 1
• Patients receiving HAART who have changed their antiretroviral regimen due to safety or efficacy associated to HIV treatment within the last 3 months prior to Day 1. However, if changes are required to a patient's HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. The patient should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, <40 copies/ mL
• Use of prohibited HAART regimens within 1 month of Day 1 and throughout the treatment period of the trial (patients receiving HAART who have changed their antiretroviral regimen to initiate any HCV treatment within 6 weeks prior to Day 1)

• Laboratory values:

  1. Neutrophil count <1500 cells/μL (<1200 cells/ μL for Blacks)
  2. Platelet count <90,000 cells/μL
  3. Hemoglobin ≤12 g/dL for females, hemoglobin ≤13 g/dL for males
  4. Total bilirubin ≥34 μmol/L (or ≥2 mg/dL) unless a patient has a documented history of Gilbert's disease or antiretroviral regimen contains atazanavir
  5. Alanine aminotransferase ≥5*upper limit of normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Daclatsvir + Ribavirin + PEG-Interferon alfa-2a

Drug: Daclatasvir; Tablets; oral; 30, 60, or 90 mg; once daily; up to 24 weeks; Other Names: BMS-790052; Drug: Ribavirin; Tablets; oral; for patients weighing <75 kg, the total dose is 1000 mg per day (2 200-mg tablets in the morning and 3 200-mg tablets in the evening); for patients weighing >75 kg, the total dose is 1200 mg per day (3 200-mg tablets in morning and 3 200-mg tablets in evening); twice daily with food; 24 or 48 weeks depending on response; Other Names: Copegus®; Drug: PEG-Interferon alfa 2a; Syringe, subcutaneous injection, 180 μg, once weekly, 24 or 48 weeks depending on response; Other Names: Pegasys®; Pegylated interferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)	SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.	Follow-up Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND)	Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.	Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND)	Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.	Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24
Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL	Participants who received HAART, maintained HIV RNA <40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined.	End of treatment (up to Week 48)
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene	Percentages calculated as number of responders/number who received treatment.	Follow-up Week 12
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation	Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy.	From Day 1 to 7 days post last dose of study treatment (up to Week 48)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Sulkowski MS, Fessel WJ, Lazzarin A, Berenguer J, Zakharova N, Cheinquer H, Cote P, Dieterich D, Gadano A, Matthews G, Molina JM, Moreno C, Pineda JA, Pulido F, Rivero A, Rockstroh J, Hernandez D, McPhee F, Eley T, Liu Z, Mendez P, Hughes E, Noviello S, Ackerman P. Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study. Hepatol Int. 2017 Mar;11(2):188-198. doi: 10.1007/s12072-017-9788-z. Epub 2017 Feb 16.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: November 4, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (ESTIMATE): November 15, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 29, 2016
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: AI444-043; 2011-003067-30 (EUDRACT_NUMBER)