A Phase 3 Study to Evaluate Combination Therapy With Daclatasvir and Sofosbuvir in the Treatment of HIV and Hepatitis C Virus Coinfection.
- Registration Number
- NCT02032888
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
A study of the efficacy and safety of the combination of daclatasvir and sofosbuvir in the treatment of hepatitis C virus and HIV coinfection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 238
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Daclatasvir + Sofosbuvir (Treatment-experienced) 12 weeks Sofosbuvir Treatment-experienced participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks Daclatasvir + Sofosbuvir (Treatment-naive) 12 weeks Sofosbuvir Treatment-naïve participants received daclatasvir 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks Daclatasvir + Sofosbuvir (Treatment-naive) 12 weeks Daclatasvir Treatment-naïve participants received daclatasvir 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks Daclatasvir + Sofosbuvir (Treatment-naive) 8 weeks Daclatasvir Treatment-naïve participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 8 weeks Daclatasvir + Sofosbuvir (Treatment-naive) 8 weeks Sofosbuvir Treatment-naïve participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 8 weeks Daclatasvir + Sofosbuvir (Treatment-experienced) 12 weeks Daclatasvir Treatment-experienced participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks
- Primary Outcome Measures
Name Time Method Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) At follow-up Week 12 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
Name Time Method Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) At follow-up Week 12 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) At follow-up Week 12 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) At follow-up Week 12 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 Week 1, 2, 4, 6, 8, 12, End of treatment, and follow-up Week 4 and 24 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) At Weeks 1, 2, 4, 6, 8, and 12 and at End of Treatment 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) At Follow-up Week 12 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 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) 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 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. 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 From screening up to week 24 of post treatment follow--up 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.
Trial Locations
- Locations (37)
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
Tarrant County Inf Dis Assoc
🇺🇸Fort Worth, Texas, United States
Clinical Research Centers Of America
🇺🇸Murray, Utah, United States
Peter J Ruane Md Inc
🇺🇸Los Angeles, California, United States
Digestive Disease Associates, P.A.
🇺🇸Baltimore, Maryland, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Cure C Consortium
🇺🇸Houston, Texas, United States
University Of Texas Health Science Center At Houston
🇺🇸Houston, Texas, United States
Precision Research Institute, Llc
🇺🇸San Diego, California, United States
Ucsd Antiviral Research Center (Avrc)
🇺🇸San Diego, California, United States
University Of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University Of California San Francisco
🇺🇸San Francisco, California, United States
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
University Of Alabama At Birmingham
🇺🇸Birmingham, Alabama, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Oregon Health Science Univ
🇺🇸Portland, Oregon, United States
Jeffrey Goodman Special Care Clinic
🇺🇸Los Angeles, California, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
Va Long Beach Healthcare System
🇺🇸Long Beach, California, United States
Anthony M. Mills Md Inc
🇺🇸Los Angeles, California, United States
Medstar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Whitman Walker Health
🇺🇸Washington, District of Columbia, United States
University Of Miami Schiff Center For Liver Diseases
🇺🇸Miami, Florida, United States
Capital Medical Associates
🇺🇸Washington, District of Columbia, United States
Infect. Disease Specialists
🇺🇸Decatur, Georgia, United States
Indiana University Health - University Hospital
🇺🇸Indianapolis, Indiana, United States
Johns Hopkins University
🇺🇸Lutherville, Maryland, United States
Southwest Care Center
🇺🇸Sante Fe, New Mexico, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Icahn School Of Medicine At Mount Sinai
🇺🇸New York, New York, United States
Binghamton Gastroenterology Associates
🇺🇸Binghamton, New York, United States
Healthcare Research Consultants
🇺🇸Tulsa, Oklahoma, United States
Mcguire D V A M C
🇺🇸Richmond, Virginia, United States
Midway Immunology And Research Center
🇺🇸Fort Pierce, Florida, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States