Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)
FOURward
1 other identifier
interventional
35
1 country
7
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2014
Shorter than P25 for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 25, 2014
CompletedFirst Posted
Study publicly available on registry
June 26, 2014
CompletedStudy Start
First participant enrolled
July 28, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 28, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
December 17, 2015
CompletedResults Posted
Study results publicly available
May 29, 2019
CompletedAugust 11, 2020
August 1, 2020
6 months
June 25, 2014
March 22, 2019
August 7, 2020
Conditions
Outcome Measures
Primary Outcomes (3)
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
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.
12 Weeks after treatment discontinuation (Follow-up Week 12)
Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment
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.
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities
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.
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Secondary Outcomes (5)
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 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 HCV Geno Subtype 1a vs 1b
Post-treatment Week 12
Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)
Post-treatment Week 12
Study Arms (4)
Arm 1: DCV/ASV/BMS-791325+Sofosbuvir
EXPERIMENTALInitial 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
EXPERIMENTALInitial 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
EXPERIMENTALDaclatasvir/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
OTHERSofosbuvir 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
Interventions
Eligibility Criteria
You may qualify if:
- 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.)
You may not qualify if:
- HCV Genotype other than Genotype 1
- Documented or suspected hepatocellular carcinoma
- Evidence of decompensated liver disease
- Contraindication(s) to Peg/RBV therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Inland Empire Liver Foundation
Rialto, California, 92377, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Northwestern University Feinberg School Of Medicine
Chicago, Illinois, 60611, United States
Indiana University Health - University Hospital
Indianapolis, Indiana, 46202, United States
Indiana University Med Center
Indianapolis, Indiana, 46202, United States
Johns Hopkins University
Lutherville, Maryland, 21093, United States
Texas Liver Institute
San Antonio, Texas, 78215, United States
Related Publications (1)
Sulkowski MS, Flamm S, Kayali Z, Lawitz EJ, Kwo P, McPhee F, Torbeyns A, Hughes EA, Swenson ES, Yin PD, Linaberry M. Short-duration treatment for chronic hepatitis C virus with daclatasvir, asunaprevir, beclabuvir and sofosbuvir (FOURward study). Liver Int. 2017 Jun;37(6):836-842. doi: 10.1111/liv.13335. Epub 2017 Feb 2.
PMID: 27943563DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 25, 2014
First Posted
June 26, 2014
Study Start
July 28, 2014
Primary Completion
January 28, 2015
Study Completion
December 17, 2015
Last Updated
August 11, 2020
Results First Posted
May 29, 2019
Record last verified: 2020-08