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CompletedNCT02175966FOURwardUpdated Aug 11, 2020Results posted

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

A Phase 2 interventional study of DCV/ASV/BMS-791325 and Ribavirin in Hepatitis C, sponsored by Bristol-Myers Squibb. Completed at 7 sites in United States. Per ClinicalTrials.gov, last updated 2020-08-11.

Sponsored by Bristol-Myers Squibb · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
35
Allocation
Randomized
Sex
All
01

Study 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.

Read the 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

02

Conditions studied

  • Hepatitis C
03

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 35 is below the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.

Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion 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

Exclusion Criteria:

  • HCV Genotype other than Genotype 1
  • Documented or suspected hepatocellular carcinoma
  • Evidence of decompensated liver disease
  • Contraindication(s) to Peg/RBV therapy
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
35 participants (actual)

Study arms

  • 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

  • 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

  • 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: Ribavirin · Drug: Sofosbuvir · Drug: Peginterferon α-2a

Interventions

  • DrugDCV/ASV/BMS-791325
  • DrugRibavirin
  • DrugSofosbuvir

    Also known as: Sovaldi®

  • DrugPeginterferon α-2a
06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 12 Weeks after treatment discontinuation (Follow-up Week 12)

  2. 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.

    Time frame: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)

  3. 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.

    Time frame: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)

Secondary outcomes

  1. 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.

    Time frame: End of the treatment

  2. 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).

    Time frame: Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24)

  3. 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).

    Time frame: Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24

  4. 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

    Time frame: Post-treatment Week 12

  5. 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.

    Time frame: Post-treatment Week 12

07

Results

Posted May 29, 2019

Participant flow

Treatment Period
Participant flow — Treatment Period
Milestone4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Started1414
Completed1414
Not completed00
Follow-up Period
Participant flow — Follow-up Period
Milestone4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Started1414
Completed48
Not completed106
Withdrew: Lack of efficacy106

Outcome measures

PrimaryPercentage 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.

Time frame:
12 Weeks after treatment discontinuation (Follow-up Week 12)
Reported as:
Number · Percentage of participants
Percentage of Participants With Sustained Virologic Response 12 (SVR12)
Percentage of participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Percentage of Participants With Sustained Virologic Response 12 (SVR12)28.6 (13.1 to 49.2)57.1 (36.9 to 75.7)
SecondaryPercentage 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.

Time frame:
End of the treatment
Reported as:
Number · Percentage of participants
Percentage of Participants With End of Treatment Response (EOTR)
Percentage of participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Percentage of Participants With End of Treatment Response (EOTR)92.9 (66.1 to 99.8)100.0 (76.8 to 100.0)
PrimaryNumber 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.

Time frame:
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Reported as:
Count of participants · Participants
Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment
Participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Death00
Serious Adverse Events10
AEs Leading to Discontinuation00
PrimaryNumber 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.

Time frame:
From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)
Reported as:
Count of participants · Participants
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities
Participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Number of Participants With Selected Grade 3/4 Laboratory Abnormalities00
SecondaryPercentage 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).

Time frame:
Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24)
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND
Percentage of Participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Week 135.7 (12.8 to 64.9)71.4 (41.9 to 91.6)
Week 278.6 (49.2 to 95.3)100.0 (76.8 to 100.0)
Week 4100.0 (76.8 to 100.0)100.0 (76.8 to 100.0)
Week 6NA (NA to NA)100.0 (76.8 to 100.0)
Follow-Up Week 278.6 (49.2 to 95.3)100.0 (76.8 to 100.0)
Follow-Up Week 442.9 (17.7 to 71.1)78.6 (49.2 to 95.3)
Follow-Up Week 1228.6 (8.4 to 58.1)57.1 (28.9 to 82.3)
Follow-Up Week 2428.6 (8.4 to 58.1)57.1 (28.9 to 82.3)
SecondaryPercentage 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).

Time frame:
Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24
Reported as:
Number · Percentage of participants
Percentage of Participants Who Achieved HCV RNA < LLOQ TND
Percentage of participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Week 121.4 (4.7 to 50.8)7.1 (0.2 to 33.9)
Week 242.9 (17.7 to 71.1)64.3 (35.1 to 87.2)
Week 492.9 (66.1 to 99.8)100.0 (76.8 to 100.0)
Week 6NA (NA to NA)100.0 (76.8 to 100.0)
Follow-Up Week 271.4 (41.9 to 91.6)92.9 (66.1 to 99.8)
Follow-Up Week 442.9 (17.7 to 71.1)71.4 (41.9 to 91.6)
Follow-Up Week 1228.6 (8.4 to 58.1)57.1 (28.9 to 82.3)
Follow-Up Week 2428.6 (8.4 to 58.1)57.1 (28.9 to 82.3)
SecondaryPercentage 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

Time frame:
Post-treatment Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b
Percentage of Participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
Genotype 1a27.354.5
Genotype 1b33.366.7
SecondaryPercentage 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.

Time frame:
Post-treatment Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)
Percentage of Participants4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
CC genotype40.066.7
Non-CC Genotype22.250.0

Adverse events

Collected over All AEs were collected from signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
4 Weeks DCV 3DAA + SOF0/14 (0%)1/14 (7.1%)5/14 (35.7%)
6 Weeks DCV 3DAA + SOF0/14 (0%)0/14 (0%)11/14 (78.6%)
Most frequent serious events
Most frequent serious events
Event4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
OverdoseInjury, poisoning and procedural complications1/140/14
Most frequent other events
Showing 10 of 29
Most frequent other events
Event4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOF
FATIGUEGeneral disorders3/144/14
HEADACHENervous system disorders2/143/14
NAUSEAGastrointestinal disorders2/141/14
INSOMNIAPsychiatric disorders0/142/14
CHEST DISCOMFORTGeneral disorders0/141/14
CHILLSGeneral disorders1/140/14
OEDEMA PERIPHERALGeneral disorders1/140/14
PYREXIAGeneral disorders1/140/14
DIARRHOEAGastrointestinal disorders1/141/14
CONSTIPATIONGastrointestinal disorders0/141/14

Baseline characteristics

All treated participants.

Age, Continuous
Age, Continuous(years)4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOFTotal
Median58.0 (21 to 64)59.0 (31 to 64)58.5 (21 to 64)
Sex: Female, Male
Sex: Female, Male(Participants)4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOFTotal
Female9817
Male5611
Race (NIH/OMB)
Race (NIH/OMB)(Participants)4 Weeks DCV 3DAA + SOF6 Weeks DCV 3DAA + SOFTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American112
White121325
More than one race000
Unknown or Not Reported000
08

Study locations

7 sites
  • 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
09

References and documents

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. PubMed 27943563 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 11, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02175966
Lead sponsor
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Jun 26, 2014
Start date
Jul 28, 2014
Primary completion
Jan 28, 2015
Completion
Dec 17, 2015
Results posted
May 29, 2019
Last update
Aug 11, 2020

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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