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

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ClinicalTrials.gov Identifier: NCT02175966
Recruitment Status : Completed
First Posted : June 26, 2014
Results First Posted : May 29, 2019
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE June 25, 2014
First Posted Date  ICMJE June 26, 2014
Results First Submitted Date  ICMJE March 22, 2019
Results First Posted Date  ICMJE May 29, 2019
Last Update Posted Date August 11, 2020
Actual Study Start Date  ICMJE July 28, 2014
Actual Primary Completion Date January 28, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
  • Proportion of treated subjects with SVR12, defined as HCV RNA <LOQ target detected or target not detected (LOQ TD/TND) for each treatment arm [ Time Frame: Post-treatment Week 12 ]
    Sustained Virologic Response (SVR) Hepatitis C virus (HCV)
  • On-treatment safety, as measured by frequency of deaths, SAEs, discontinuations due to AEs, and Grade 3/4 laboratory abnormalities (hematologic and liver function, based on DAIDs criteria) by each arm and overall [ Time Frame: Up to post-treatment week 4 ]
    Serious AE (SAE) Adverse Event (AE) Division of AIDs (DAIDS)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • 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.
  • 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).
  • 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).
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
  • Proportion of subjects in each arm who achieve HCV RNA <LOQ TD/TND [ Time Frame: Weeks 1, 2, 4 and 6 (Arm 2 only); post-treatment Weeks 2 (SVR2), 4 (SVR4) and 24 (SVR24) ]
  • Proportion of subjects in each arm who achieve HCV RNA <LOQ TND [ Time Frame: Weeks 1, 2, 4 and 6 (Arm 2 only); and post-treatment Weeks 2, 4, 12 and 24 ]
  • Proportion of subjects in each arm achieving SVR12 associated with HCV geno subtype 1a vs 1b [ Time Frame: Post-treatment Week 12 ]
  • Proportion of subjects in each arm achieving SVR12 associated with interleukin-28B (IL28B) rs12979860 SNP status (CC genotype or non-CC genotype) [ Time Frame: Post-treatment Week 12 ]
    Single nucleotide polymorphism (SNP)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)
Official Title  ICMJE Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: DCV/ASV/BMS-791325
  • Drug: Ribavirin
  • Drug: Sofosbuvir
    Other Name: Sovaldi®
  • Drug: Peginterferon α-2a
Study Arms  ICMJE
  • 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

    Interventions:
    • Drug: DCV/ASV/BMS-791325
    • Drug: Sofosbuvir
  • 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

    Interventions:
    • Drug: DCV/ASV/BMS-791325
    • Drug: Sofosbuvir
  • 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

    Interventions:
    • Drug: DCV/ASV/BMS-791325
    • Drug: Ribavirin
    • Drug: 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

    Interventions:
    • Drug: Ribavirin
    • Drug: Sofosbuvir
    • Drug: Peginterferon α-2a
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 6, 2019)
35
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2014)
30
Actual Study Completion Date  ICMJE December 17, 2015
Actual Primary Completion Date January 28, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02175966
Other Study ID Numbers  ICMJE AI443-131
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP