Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)
Overview
- Phase
- Phase 2
- Intervention
- DCV/ASV/BMS-791325
- Conditions
- Hepatitis C
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 35
- Locations
- 7
- Primary Endpoint
- Percentage of Participants With Sustained Virologic Response 12 (SVR12)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.)
Exclusion Criteria
- •HCV Genotype other than Genotype 1
- •Documented or suspected hepatocellular carcinoma
- •Evidence of decompensated liver disease
- •Contraindication(s) to Peg/RBV therapy
Arms & Interventions
Arm 1: DCV/ASV/BMS-791325+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
Intervention: DCV/ASV/BMS-791325
Arm 1: DCV/ASV/BMS-791325+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
Intervention: Sofosbuvir
Arm 2: DCV/ASV/BMS-791325 + 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
Intervention: DCV/ASV/BMS-791325
Arm 2: DCV/ASV/BMS-791325 + 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
Intervention: Sofosbuvir
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-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
Intervention: DCV/ASV/BMS-791325
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-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
Intervention: Ribavirin
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-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
Intervention: Peginterferon α-2a
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-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
Intervention: Ribavirin
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-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
Intervention: Sofosbuvir
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-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
Intervention: Peginterferon α-2a
Outcomes
Primary Outcomes
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- Percentage of Participants With End of Treatment Response (EOTR)(End of the 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 Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b(Post-treatment Week 12)
- 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 Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)(Post-treatment Week 12)