Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant
- Registration Number
- NCT02032875
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
This trial was open to participants who had received a liver transplant or had cirrhosis due to chronic HCV. All subjects were treated with daclatasvir+sofosbuvir+ribavirin and were followed for 24 weeks post treatment. Under certain conditions, the treatment duration could have been extended for cirrhotic participants. The study tested the efficacy and safety of this combination for treatment of HCV in cirrhotic and post transplant patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 116
- Participants 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
- Participants chronically infected with hepatitis C virus (HCV) Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥10,000 IU/mL at screening
- Participants may be treatment-naïve or treatment-experienced
- Cirrhotic participants must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol
- Post-transplant participants must be at least 3 months post-transplant with no evidence of moderate or severe rejection
- History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited
- Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening
- Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures)
- History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Participants with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative)
- Active hospitalization for decompensated liver disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Post-liver Transplant Cohort Daclatasvir Participants with liver transplant received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets daily for 12 weeks and were followed for 24 weeks post treatment. Post-liver Transplant Cohort Sofosbuvir Participants with liver transplant received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets daily for 12 weeks and were followed for 24 weeks post treatment. Post-liver Transplant Cohort Ribavirin Participants with liver transplant received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets daily for 12 weeks and were followed for 24 weeks post treatment. Cirrhotic Cohort Daclatasvir Cirrhotic participants received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets orally for 12 weeks and were followed for 24 weeks post-treatment. Cirrhotic participants who received a liver transplant while on study treatment were eligible (\>3 months post transplant) for a treatment extension of daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (dose based on hemoglobin level) tablets orally for an additional 12 weeks Cirrhotic Cohort Sofosbuvir Cirrhotic participants received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets orally for 12 weeks and were followed for 24 weeks post-treatment. Cirrhotic participants who received a liver transplant while on study treatment were eligible (\>3 months post transplant) for a treatment extension of daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (dose based on hemoglobin level) tablets orally for an additional 12 weeks Cirrhotic Cohort Ribavirin Cirrhotic participants received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets orally for 12 weeks and were followed for 24 weeks post-treatment. Cirrhotic participants who received a liver transplant while on study treatment were eligible (\>3 months post transplant) for a treatment extension of daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (dose based on hemoglobin level) tablets orally for an additional 12 weeks
- Primary Outcome Measures
Name Time Method Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) Post-treatment follow-up Week 12 SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (\<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment 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 Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) Post-treatment follow-up Week 12 SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment 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 Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6 Post-treatment follow-up Week 12 SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment 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 With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12) Post-treatment follow-up Week 12 Participants categorized into 2 genotypes (CC and non-CC) based on single nucleotide polymorphism in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus RNA levels be \<lower limit of quantitation ie, 25 IU/mL or below 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.
Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities From start of study treatment up to 7 days post last dose of study treatment Grade 3-4 laboratory abnormalities were defined as: Hemoglobin as 6.50-7.4 g/dL for grade 3 and/or \< 6.5 g/dL for grade 4, Platelet count as 25\*10\^9-50\*10\^9 /L for grade 3 and/or \< 25.000\*10\^9 /L for grade 4, International normalized ratio as 2.1-3.0\*upper limit of normal (ULN) \> 3.0\*ULN for grade 3 and/or \> 3.0\*ULN for grade 4, Leukocytes as 1.0\*10\^9-1.5\*10\^9/L for grade 3 and/or \<1.0\*10\^9/L for grade 4, Lymphocytes (Absolute) as 0.350\*109-0.499\*10\^9 /L for grade 3 and/or \< 0.350\*10\^9 /L for grade 4, Alanine aminotransferase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Aspartate aminotransferase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Alkaline phosphatase as 5.1-10.0\*ULN for grade 3 and/or \> 10.0\*ULN for grade 4, Bilirubin (Total) as 2.6-5.0\*ULN for grade 3 and/or \> 5.0\*ULN for grade 4, Albumin as \< 20 g/L, Lipase (Total) as 3.1-5.0\*ULN for grade 3 and/or \> 5.0\*ULN for grade 4, and Creatinine as 1.9-3.4\*ULN for grade 3 and/or ≥ 3.5\*ULN for grade 4.
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24 Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24 Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit.
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment Week 1, 2, 4, 6, 8, 12, End of treatment Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit.
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks) AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does 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.
Trial Locations
- Locations (5)
University Of Miami Schiff Center For Liver Diseases
🇺🇸Miami, Florida, United States
University Of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Baylor St. Luke'S Medical Center
🇺🇸Houston, Texas, United States
American Research Corporation
🇺🇸San Antonio, Texas, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States