Hepatitis CPhase 2FOURwardNCT02175966
Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)
A Phase 2 study testing DCV/ASV/BMS-791325, Ribavirin and Sofosbuvir in people with Hepatitis C, run by Bristol-Myers Squibb at 7 sites in United States.
Trial 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 more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hepatitis C
- What is being tested?
- DCV/ASV/BMS-791325, Ribavirin and Sofosbuvir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 7 sitesUnited States
- Study dates
- 28 Jul 2014to 17 Dec 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.)
Who cannot join
- HCV Genotype other than Genotype 1
- Documented or suspected hepatocellular carcinoma
- Evidence of decompensated liver disease
- Contraindication(s) to Peg/RBV therapy
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Northwestern University Feinberg School Of Medicine
Chicago, Illinois, 60611
Indiana University Health - University Hospital
Indianapolis, Indiana, 46202
Indiana University Med Center
Indianapolis, Indiana, 46202
Johns Hopkins University
Lutherville, Maryland, 21093
Inland Empire Liver Foundation
Rialto, California, 92377
Texas Liver Institute
San Antonio, Texas, 78215
About this study
Official title: 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.
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
- Conditions
- Hepatitis C
- Being tested
- DCV/ASV/BMS-791325, Ribavirin, Sofosbuvir, Peginterferon α-2a
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DCV/ASV/BMS-791325Drug
RibavirinDrug
SofosbuvirDrug
Also called Sovaldi®
Peginterferon α-2aDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: DCV/ASV/BMS-791325+Sofosbuvir | Experimental | 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 Receives: Drug: DCV/ASV/BMS-791325; Drug: Sofosbuvir |
| Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir | Experimental | 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 Receives: Drug: DCV/ASV/BMS-791325; Drug: Sofosbuvir |
| Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a | Experimental | 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 Receives: Drug: DCV/ASV/BMS-791325; Drug: Ribavirin; Drug: Peginterferon α-2a |
| Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a | Other | 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 Receives: Drug: Ribavirin; Drug: Sofosbuvir; Drug: Peginterferon α-2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)
EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment.
Measured: End of the 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).
Measured: 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
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).
Measured: 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
Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b
Measured: Post-treatment Week 12
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.
Measured: Post-treatment Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2014 (estimated)
- Study start28 Jul 2014
- Primary completion28 Jan 2015
- Study completion17 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02175966
- Sponsor's protocol ID
- AI443-131
- Acronym
- FOURward
- Status last verified
- Aug 2020
- First submitted
- 25 Jun 2014
- Last updated
- 11 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)
- ClinicalTrials.gov ID
- NCT02175966
- Acronym / sponsor ID
- FOURward / AI443-131
- Conditions
- Hepatitis C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 28 Jul 2014 (actual)
- Primary completion
- 28 Jan 2015 (actual)
- Study completion
- 17 Dec 2015 (actual)
- First posted
- 26 Jun 2014 (estimated)
- Results
- Posted 29 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1: DCV/ASV/BMS-791325+Sofosbuvir | Experimental | Drug: DCV/ASV/BMS-791325, Drug: SofosbuvirInitial 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 | Experimental | Drug: DCV/ASV/BMS-791325, Drug: SofosbuvirInitial 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 | Experimental | Drug: DCV/ASV/BMS-791325, Drug: Ribavirin, Drug: Peginterferon α-2aDaclatasvir/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 | Other | Drug: Ribavirin, Drug: Sofosbuvir, Drug: Peginterferon α-2aSofosbuvir 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.)
Key exclusion criteria (4 listed)
- HCV Genotype other than Genotype 1
- Documented or suspected hepatocellular carcinoma
- Evidence of decompensated liver disease
- Contraindication(s) to Peg/RBV therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DCV/ASV/BMS-791325 | Drug | 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 |
| Ribavirin | Drug | Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a, Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a |
| SofosbuvirAlso: Sovaldi® | Drug | Arm 1: DCV/ASV/BMS-791325+Sofosbuvir, Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir, Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a |
| Peginterferon α-2a | Drug | Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a, Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a |
Primary outcome
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.
5 secondary outcomes
Percentage of Participants With End of Treatment Response (EOTR)
Time frame: 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 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 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 Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)
Time frame: Post-treatment Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27943563Sulkowski 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DCV/ASV/BMS-791325, Ribavirin and Sofosbuvir in people with Hepatitis C, run by Bristol-Myers Squibb at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Sustained Virologic Response 12 (SVR12) (time frame: 12 Weeks after treatment discontinuation (Follow-up Week 12)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02175966, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.