Back to resultsShort Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study) (FOURward)
Primary Purpose
Hepatitis C
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
DCV/ASV/BMS-791325
Ribavirin
Sofosbuvir
Peginterferon α-2a
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
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
Sites / Locations
- Inland Empire Liver Foundation
- Northwestern Memorial Hospital
- Northwestern University Feinberg School Of Medicine
- Indiana University Health - University Hospital
- Indiana University Med Center
- Johns Hopkins University
- Texas Liver Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Other
Arm Label
Arm 1: DCV/ASV/BMS-791325+Sofosbuvir
Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a
Arm Description
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
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
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
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
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
Percentage of Participants With End of Treatment Response (EOTR)
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
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 HCV RNA < LLOQ TND
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 HCV Geno Subtype 1a vs 1b
Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b
Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)
Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02175966
Brief Title
Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)
Acronym
FOURward
Official Title
Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
July 28, 2014 (Actual)
Primary Completion Date
January 28, 2015 (Actual)
Study Completion Date
December 17, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: DCV/ASV/BMS-791325+Sofosbuvir
Arm Type
Experimental
Arm Description
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 Title
Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir
Arm Type
Experimental
Arm Description
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
Arm Title
Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a
Arm Type
Experimental
Arm Description
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 Title
Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a
Arm Type
Other
Arm Description
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 Type
Drug
Intervention Name(s)
DCV/ASV/BMS-791325
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Other Intervention Name(s)
Sovaldi®
Intervention Type
Drug
Intervention Name(s)
Peginterferon α-2a
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
Description
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.
Time Frame
12 Weeks after treatment discontinuation (Follow-up Week 12)
Title
Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment
Description
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.
Time Frame
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Title
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities
Description
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.
Time Frame
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Secondary Outcome Measure Information:
Title
Percentage of Participants With End of Treatment Response (EOTR)
Description
EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment.
Time Frame
End of the treatment
Title
Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND
Description
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).
Time Frame
Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24)
Title
Percentage of Participants Who Achieved HCV RNA < LLOQ TND
Description
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).
Time Frame
Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24
Title
Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b
Description
Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b
Time Frame
Post-treatment Week 12
Title
Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)
Description
Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.
Time Frame
Post-treatment Week 12
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Inland Empire Liver Foundation
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Northwestern University Feinberg School Of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University Health - University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Indiana University Med Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Johns Hopkins University
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
Facility Name
Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27943563
Citation
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.
Results Reference
derived
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting
Learn more about this trial
Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)
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