Hepatitis CPhase 3ALLY 1NCT02032875
Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant
A Phase 3 study testing Daclatasvir, Sofosbuvir and Ribavirin in people with Hepatitis C, run by Bristol-Myers Squibb at 5 sites in United States.
Trial summary
This trial was open to participants who had received a liver transplant or had cirrhosis due to chronic HCV. All subjects were treated with daclatasvir+sofosbuvir+ribavirin and were followed for 24 weeks post treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Daclatasvir, Sofosbuvir and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2014to Jan 2016
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
- Participants chronically infected with hepatitis C virus (HCV) Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥10,000 IU/mL at screening
- Participants may be treatment-naïve or treatment-experienced
- Cirrhotic participants must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol
- Post-transplant participants must be at least 3 months post-transplant with no evidence of moderate or severe rejection
Who cannot join
- History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited
- Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening
- Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures)
- History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Participants with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative)
- Active hospitalization for decompensated liver disease
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University Of Michigan Health System
Ann Arbor, Michigan, 48109
Baylor St. Luke'S Medical Center
Houston, Texas, 77030
University Of Miami Schiff Center For Liver Diseases
Miami, Florida, 33136
American Research Corporation
San Antonio, Texas, 78215
Harborview Medical Center
Seattle, Washington, 98104
About this study
Official title: A Phase 3 Evaluation of Daclatasvir, Sofosbuvir, and Ribavirin in Genotype 1-6 Chronic Hepatitis C Infection Subjects With Cirrhosis Who May Require Future Liver Transplant and Subjects Post-Liver Transplant
This trial was open to participants who had received a liver transplant or had cirrhosis due to chronic HCV. All subjects were treated with daclatasvir+sofosbuvir+ribavirin and were followed for 24 weeks post treatment. Under certain conditions, the treatment duration could have been extended for cirrhotic participants. The study tested the efficacy and safety of this combination for treatment of HCV in cirrhotic and post transplant patients.
- Conditions
- Hepatitis C
- Being tested
- Daclatasvir, Sofosbuvir, Ribavirin
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclatasvirDrug
Also called BMS-790052
SofosbuvirDrug
RibavirinDrug
| Study group | Role | What they receive |
|---|---|---|
| Post-liver Transplant Cohort | Experimental | Participants with liver transplant received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets daily for 12 weeks and were followed for 24 weeks post treatment. Receives: Drug: Daclatasvir; Drug: Sofosbuvir; Drug: Ribavirin |
| Cirrhotic Cohort | Experimental | Cirrhotic participants received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets orally for 12 weeks and were followed for 24 weeks post-treatment. Cirrhotic participants who received a liver transplant while on study treatment were eligible (>3 months post transplant) for a treatment extension of daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (dose based on hemoglobin level) tablets orally for an additional 12 weeks Receives: Drug: Daclatasvir; Drug: Sofosbuvir; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Measured: Post-treatment follow-up Week 12
Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Measured: Post-treatment follow-up Week 12
Secondary outcomes (6)
Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Measured: Post-treatment follow-up Week 12
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24
Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit.
Measured: Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment
Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels below the lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit.
Measured: Week 1, 2, 4, 6, 8, 12, End of treatment
Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12)
Participants categorized into 2 genotypes (CC and non-CC) based on single nucleotide polymorphism in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus RNA levels be <lower limit of quantitation ie, 25 IU/mL or below target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Measured: Post-treatment follow-up Week 12
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death
AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.
Measured: From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks)
Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities
Grade 3-4 laboratory abnormalities were defined as: Hemoglobin as 6.50-7.4 g/dL for grade 3 and/or < 6.5 g/dL for grade 4, Platelet count as 25*10^9-50*10^9 /L for grade 3 and/or < 25.000*10^9 /L for grade 4, International normalized ratio as 2.1-3.0*upper limit of normal (ULN) > 3.0*ULN for grade 3 and/or > 3.0*ULN for grade 4, Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and/or <1.0*10^9/L for grade 4, Lymphocytes (Absolute) as 0.350*109-0.499*10^9 /L for grade 3 and/or < 0.350*10^9 /L for grade 4, Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Alkaline phosphatase as 5.1-10.0*ULN for grade 3 and/or > 10.0*ULN for grade 4, Bilirubin (Total) as 2.6-5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4, Albumin as < 20 g/L, Lipase (Total) as 3.1-5.0*ULN for grade 3 and/or > 5.0*ULN for grade 4, and Creatinine as 1.9-3.4*ULN for grade 3 and/or ≥ 3.5*ULN for grade 4.
Measured: From start of study treatment up to 7 days post last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2014 (estimated)
- Study startMar 2014
- Primary completionNov 2014
- Study completionJan 2016
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 116 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
- NCT02032875
- Sponsor's protocol ID
- AI444-215
- Acronym
- ALLY 1
- Status last verified
- Dec 2016
- First submitted
- 9 Jan 2014
- Last updated
- 9 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Evaluation of Daclatasvir, Sofosbuvir, and Ribavirin in Genotype 1-6 Chronic Hepatitis C Infection Subjects With Cirrhosis Who May Require Future Liver Transplant and Subjects Post-Liver Transplant
- ClinicalTrials.gov ID
- NCT02032875
- Acronym / sponsor ID
- ALLY 1 / AI444-215
- Conditions
- Hepatitis C
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- Nov 2014 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 10 Jan 2014 (estimated)
- Results
- Posted 20 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial was open to participants who had received a liver transplant or had cirrhosis due to chronic HCV. All subjects were treated with daclatasvir+sofosbuvir+ribavirin and were followed for 24 weeks post treatment. Under certain conditions, the treatment duration could have been extended for cirrhotic participants. The study tested the efficacy and safety of this combination for treatment of HCV in cirrhotic and post transplant patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Post-liver Transplant Cohort | Experimental | Drug: Daclatasvir, Drug: Sofosbuvir, Drug: RibavirinParticipants with liver transplant received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets daily for 12 weeks and were followed for 24 weeks post treatment. |
| Cirrhotic Cohort | Experimental | Drug: Daclatasvir, Drug: Sofosbuvir, Drug: RibavirinCirrhotic participants received daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (based on baseline hemoglobin and creatinine clearance and tolerated dose) tablets orally for 12 weeks and were followed for 24 weeks post-treatment. Cirrhotic participants who received a liver transplant while on study treatment were eligible (>3 months post transplant) for a treatment extension of daclatasvir 60 mg, sofosbuvir 400 mg, and ribavirin (dose based on hemoglobin level) tablets orally for an additional 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participants must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications
- Participants chronically infected with hepatitis C virus (HCV) Genotype 1, 2, 3, 4, 5, or 6 with HCV RNA viral load of ≥10,000 IU/mL at screening
- Participants may be treatment-naïve or treatment-experienced
- Cirrhotic participants must have cirrhosis confirmed by biopsy, Fibroscan or fibrotest and Aspartate aminotransferase platelet ratio index (APRI) criteria as outlined in the protocol
- Post-transplant participants must be at least 3 months post-transplant with no evidence of moderate or severe rejection
Key exclusion criteria (5 listed)
- History of multi-organ transplant, with the exception of dual transplantation of the liver/kidney, is prohibited
- Current or known history of cancer (with the following exceptions: In situ carcinoma of the cervix, adequately treated basal or squamous cell carcinoma of the skin, or hepatocellular carcinoma within Milan criteria for transplantation) within 5 years prior to screening
- Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV (such as, but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, or toxin exposures)
- History of HIV infection or chronic hepatitis B virus (HBV) as documented by HBV serologies (e.g., HBsAg-seropositive). Participants with resolved HBV infection may participate (e.g., HBcAb-seropositive with concurrent HBsAg-seronegative)
- Active hospitalization for decompensated liver disease
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 |
|---|---|---|
| DaclatasvirAlso: BMS-790052 | Drug | Cirrhotic Cohort, Post-liver Transplant Cohort |
| Sofosbuvir | Drug | Cirrhotic Cohort, Post-liver Transplant Cohort |
| Ribavirin | Drug | Cirrhotic Cohort, Post-liver Transplant Cohort |
Primary outcome
Percentage of HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
Time frame: Post-treatment follow-up Week 12
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation (<LLOQ) i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
Percentage of Genotype-1 Infected Cirrhotic Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
Time frame: Post-treatment follow-up Week 12
SVR12 was defined as hepatitis C Virus (HCV) RNA levels below the lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window.
6 secondary outcomes
Percentage of Participants Who Achieved Sustained Virologic Response at Post-treatment Week 12 (SVR12) for All Genotypes and Genotypes 2, 3, 4, 6
Time frame: Post-treatment follow-up Week 12
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Detected or Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment; Follow Up Weeks 4, 8, and 24
Time frame: Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 24
Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels Below the Lower Limit of Quantitation Target Not Detected at Each of the Following Weeks: 1, 2, 4, 6, 8, 12, End of Treatment
Time frame: Week 1, 2, 4, 6, 8, 12, End of treatment
Percentage of Participants With CC or Non-CC Genotype Who Achieved Sustained Virologic Response at 12 Weeks After the Last Dose of Study Drug (SVR12)
Time frame: Post-treatment follow-up Week 12
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), AEs Leading to Interruption, Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Death
Time frame: From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks)
Number of Participants With Treatment Emergent Grade 3-4 Laboratory Abnormalities
Time frame: From start of study treatment up to 7 days post last dose of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Daclatasvir, Sofosbuvir and Ribavirin in people with Hepatitis C, run by Bristol-Myers Squibb at 5 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 5 inclusion and 5 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 9 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 20 Oct 2015). 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 HCV Genotype-1 Infected Post-liver Transplanted Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) (time frame: Post-treatment follow-up Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Feb 2017.