A Phase 3 Study to Evaluate Combination Therapy With Daclatasvir and Sofosbuvir in the Treatment of HIV and Hepatitis C Virus Coinfection.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02032888
First received: January 9, 2014
Last updated: September 24, 2015
Last verified: August 2015
  Purpose
A study of the efficacy and safety of the combination of daclatasvir and sofosbuvir in the treatment of hepatitis C virus and HIV coinfection.

Condition Intervention Phase
Hepatitis C
Drug: Daclatasvir
Drug: Sofosbuvir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C (Genotype 1, 2, 3, 4, 5, or 6) Subjects Coinfected With Human Immunodeficiency Virus (HIV)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA <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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.


Secondary Outcome Measures:
  • Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA<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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.

  • Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA <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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.

  • Percentage of Participants of All Genotypes Coinfected With Hepatitis C Virus (HCV)/HIV Who Achieved Sustained Virologic Response Rate at Follow-up Week 12 (SVR12) [ Time Frame: At follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA levels <lower limit of quantitation, target detected or target not detected. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.

  • Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels to be <Lower Limit of Quantitation, Target Detected (TD)or Target Not Detected (TND) at Weeks: 1, 2, 4, 6, 8, and 12; at End of Treatment; and at Follow-up Weeks 4 and 24 [ Time Frame: Week 1, 2, 4, 6, 8, 12, End of treatment, and follow-up Week 4 and 24 ] [ Designated as safety issue: No ]
    Participants with hepatitis C virus CV) levels to be <lower limit of quantitation, TD or TND at each visit. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Percentage of Participants Coinfected With Hepatitis C Virus/HIV Who Achieved HCV RNA Levels<Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) [ Time Frame: At Weeks 1, 2, 4, 6, 8, and 12 and at End of Treatment ] [ Designated as safety issue: No ]
    Participants with HCV RNA levels <LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

  • Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12) [ Time Frame: At Follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR is defined as hepatitis C virus RNA <lower limit of quantitation, target detected or target not detected at follow-up Week 12. Percentage calculated as number of responders/number of patients receiving treatment.

  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Interruption or Discontinuation, Treatment-related AEs/SAEs and Grade 3 to 4 AEs/SAEs and Who Died During Treatment Period [ Time Frame: AEs: Day 1 to 7 days after last dose of study treatment (8 weeks or 12 weeks). SAEs: Day 1 to 30 days after last dose of study treatment (8 weeks or 12 weeks) ] [ Designated as safety issue: Yes ]
    AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Who Died During Follow-up Period [ Time Frame: AEs: Day 1 of follow-up period (Week 9 or Week 13) to 7 days after end of 24 weeks follow-up period. SAEs: Day 1 of follow-up period (Week 9 or Week 13) to 30 days after end of 24 weeks follow-up period. ] [ Designated as safety issue: Yes ]
    AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

  • Number of Participants With Treatment-emergent Grade 3-4 Abnormalities on Laboratory Test Results [ Time Frame: From screening up to week 24 of post treatment follow--up ] [ Designated as safety issue: Yes ]
    Grade 3-4 abnormalities on laboratory test results were defined as: International normalized ratio as 2.1-3.0*upper limit of normal (ULN) for grade 3 and >3.0*ULN for grade 4. Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and <1.0*10^9/L for grade 4. Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4. Bilirubin (total) as 2.6-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Lipase (total) as 3.1-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4.


Enrollment: 238
Study Start Date: February 2014
Study Completion Date: January 2015
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daclatasvir + Sofosbuvir (Treatment-naive) 12 weeks
Treatment-naïve participants received daclatasvir 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks
Drug: Daclatasvir
Other Name: BMS-790052
Drug: Sofosbuvir
Experimental: Daclatasvir + Sofosbuvir (Treatment-naive) 8 weeks
Treatment-naïve participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 8 weeks
Drug: Daclatasvir
Other Name: BMS-790052
Drug: Sofosbuvir
Experimental: Daclatasvir + Sofosbuvir (Treatment-experienced) 12 weeks
Treatment-experienced participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks
Drug: Daclatasvir
Other Name: BMS-790052
Drug: Sofosbuvir

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Key Inclusion Criteria:

  • Patients must be able to understand and agree to/comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
  • Patients chronically infected with hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6, as documented by positive HCV RNA at screening
  • Patients who are HCV treatment-naive
  • Patients who are HCV treatment-experienced and who have had prior anti-HCV therapies discontinued or completed at least 12 weeks prior to screening
  • Patients with HCV RNA ≥10,000 IU/mL at screening
  • Patients with HIV-1 infection

Key Exclusion Criteria:

  • Presence of AIDs-defining opportunistic infections, as defined by the Centers of Disease Control and Prevention, within 12 weeks prior to study entry
  • Patients infected with HIV-2
  • Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair
  • Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening
  • Documented or suspected hepatocellular carcinoma, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed
  • Evidence of decompensated liver disease, including radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
  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: NCT02032888

  Hide Study Locations
Locations
United States, Alabama
University Of Alabama At Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Pacific Oaks Medical Group
Beverly Hills, California, United States, 90211
Va Long Beach Healthcare System
Long Beach, California, United States, 90822
Peter J Ruane Md Inc
Los Angeles, California, United States, 90036
Anthony M. Mills Md Inc
Los Angeles, California, United States, 90069
Jeffrey Goodman Special Care Clinic
Los Angeles, California, United States, 90232
Ucsd Antiviral Research Center (Avrc)
San Diego, California, United States, 92103
Precision Research Institute, Llc
San Diego, California, United States, 92114
University Of California San Francisco
San Francisco, California, United States, 94110
United States, Colorado
University Of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Capital Medical Associates
Washington, District of Columbia, United States, 20036
Medstar Washington Hospital Center
Washington, District of Columbia, United States, 20010
Whitman Walker Health
Washington, District of Columbia, United States, 20009
United States, Florida
Midway Immunology And Research Center
Fort Pierce, Florida, United States, 34982
University Of Miami Schiff Center For Liver Diseases
Miami, Florida, United States, 33136
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Georgia
Infect. Disease Specialists
Decatur, Georgia, United States, 30033
United States, Indiana
Indiana University Health - University Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
Digestive Disease Associates, P.A.
Baltimore, Maryland, United States, 21229
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School Of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Mexico
Southwest Care Center
Sante Fe, New Mexico, United States, 87505
United States, New York
Binghamton Gastroenterology Associates
Binghamton, New York, United States, 13903
Icahn School Of Medicine At Mount Sinai
New York, New York, United States, 10029
United States, Ohio
University Of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Oklahoma
Healthcare Research Consultants
Tulsa, Oklahoma, United States, 74135
United States, Oregon
Oregon Health Science Univ
Portland, Oregon, United States, 97239
United States, Pennsylvania
Lehigh Valley Health Network
Allentown, Pennsylvania, United States, 18102
United States, Rhode Island
University Gastroenterology
Providence, Rhode Island, United States, 02905
The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Texas
Tarrant County Inf Dis Assoc
Fort Worth, Texas, United States, 76104
Cure C Consortium
Houston, Texas, United States, 77004
University Of Texas Health Science Center At Houston
Houston, Texas, United States, 77030
United States, Utah
Clinical Research Centers Of America
Murray, Utah, United States, 84123
United States, Virginia
Mcguire D V A M C
Richmond, Virginia, United States, 23249
United States, Washington
Harborview Medical Center
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02032888     History of Changes
Other Study ID Numbers: AI444-216 
Study First Received: January 9, 2014
Results First Received: August 21, 2015
Last Updated: September 24, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on May 04, 2016