Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study) (FOURward)

August 7, 2020 updated by: Bristol-Myers Squibb

Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Rialto, California, United States, 92377
        • Inland Empire Liver Foundation
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Med Center
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health - University Hospital
    • Maryland
      • Lutherville, Maryland, United States, 21093
        • Johns Hopkins University
    • Texas
      • San Antonio, Texas, United States, 78215
        • Texas Liver Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: DCV/ASV/BMS-791325
Drug: Sofosbuvir
Other Names:
  • Sovaldi®
Experimental: 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
Drug: DCV/ASV/BMS-791325
Drug: Sofosbuvir
Other Names:
  • Sovaldi®
Experimental: 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
Drug: DCV/ASV/BMS-791325
Drug: Ribavirin
Drug: Peginterferon α-2a
Other: 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
Drug: Sofosbuvir
Other Names:
  • Sovaldi®
Drug: Ribavirin
Drug: Peginterferon α-2a

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
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
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.
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With End of Treatment Response (EOTR)
Time Frame: 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.
End of the treatment
Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND
Time Frame: 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).
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
Time Frame: 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).
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
Time Frame: Post-treatment Week 12
Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 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)
Time Frame: 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.
Post-treatment Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2014

Primary Completion (Actual)

January 28, 2015

Study Completion (Actual)

December 17, 2015

Study Registration Dates

First Submitted

June 25, 2014

First Submitted That Met QC Criteria

June 25, 2014

First Posted (Estimate)

June 26, 2014

Study Record Updates

Last Update Posted (Actual)

August 11, 2020

Last Update Submitted That Met QC Criteria

August 7, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AI443-131

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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