Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)
- Conditions
- Hepatitis C
- Interventions
- Registration Number
- NCT02175966
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of the study is to determine whether the combination of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325 and Sofosbuvir is effective and safe in treating Hepatitis-C virus.
- Detailed Description
Allocation:
Initial Therapy: Randomized Controlled Trial: Participants are assigned to intervention groups by chance
Rescue Therapy: Nonrandomized Trial: Participants are expressly assigned to intervention groups through a non-random method such as physician choice
Number of Arms:
Initial Therapy: 2 Groups
Rescue Therapy: 2 Groups
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
- Males and Females ≥18 years of age, inclusive
- Chronic HCV infection Genotype 1 only
- Non-cirrhotic
- Treatment naive subjects with no previous exposure to an Interferon formulation (ie, IFNα, pegIFNα), ribavirin (RBV) or HCV Direct Acting Antiviral (DAA) (protease, polymerase inhibitor, etc.)
- HCV Genotype other than Genotype 1
- Documented or suspected hepatocellular carcinoma
- Evidence of decompensated liver disease
- Contraindication(s) to Peg/RBV therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a Peginterferon α-2a Sofosbuvir 400 mg tablet once daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir DCV/ASV/BMS-791325 Initial Therapy Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 6 weeks Sofosbuvir 400 mg tablet once daily orally for 6 weeks Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a DCV/ASV/BMS-791325 Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks Arm 1: DCV/ASV/BMS-791325+Sofosbuvir DCV/ASV/BMS-791325 Initial Therapy: Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 4 weeks Sofosbuvir 400 mg tablet once daily orally for 4 weeks Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a Peginterferon α-2a Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks Arm 1: DCV/ASV/BMS-791325+Sofosbuvir Sofosbuvir Initial Therapy: Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 4 weeks Sofosbuvir 400 mg tablet once daily orally for 4 weeks Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir Sofosbuvir Initial Therapy Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 6 weeks Sofosbuvir 400 mg tablet once daily orally for 6 weeks Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a Ribavirin Daclatasvir/Asunaprevir/BMS-791325 \[30 mg (as the free base)/200 mg/75 mg (as the free base)\] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a Sofosbuvir Sofosbuvir 400 mg tablet once daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a Ribavirin Sofosbuvir 400 mg tablet once daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks
- Primary Outcome Measures
Name Time Method Percentage of Participants With Sustained Virologic Response 12 (SVR12) 12 Weeks after treatment discontinuation (Follow-up Week 12) SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) \< lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 12. Imputed SVR12 was based on Next Value Carried Backwards approach.
Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months) SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect.
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months) Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 24 data set was used to evaluate the Week-24 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With End of Treatment Response (EOTR) End of the treatment EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment.
Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24) Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24).
Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b Post-treatment Week 12 Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b
Percentage of Participants Who Achieved HCV RNA < LLOQ TND Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24 Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) \< lower limit of quantitation (LLOQ), target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), and 24 (SVR24).
Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) Post-treatment Week 12 Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.
Trial Locations
- Locations (7)
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Indiana University Health - University Hospital
🇺🇸Indianapolis, Indiana, United States
Northwestern University Feinberg School Of Medicine
🇺🇸Chicago, Illinois, United States
Indiana University Med Center
🇺🇸Indianapolis, Indiana, United States
Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Johns Hopkins University
🇺🇸Lutherville, Maryland, United States