Phase III Daclatasvir, Sofosbuvir, and Ribavirin in Cirrhotic Participants and Participants Post-liver Transplant

Hepatitis C Clinical Trial

— ALLY 1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02032875
• Other study ID #: AI444-215
• Status: Active, not recruiting
• Phase: Phase 3
• First received: January 9, 2014
• Last updated: October 20, 2015
• Start date: March 2014
• Est. completion date: January 2016

Study information

• Verified date: October 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This trial is open to participants with cirrhosis due to chronic hepatitis C virus (HCV), and to participants who have already received a liver transplant for chronic HCV. All subjects will be treated with Daclatasvir and Sofosbuvir for 12 weeks. Under certain conditions, the treatment duration may be extended for cirrhotic participants . The study will test how well this combination of investigational drugs works to treat chronic HCV.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 116
• Est. completion date: January 2016
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C

Intervention

Drug:
• Daclatasvir

• Sofosbuvir

• Ribavirin

Locations

Country	Name	City	State
United States	University Of Michigan Health System	Ann Arbor	Michigan
United States	Baylor St. Luke'S Medical Center	Houston	Texas
United States	University Of Miami Schiff Center For Liver Diseases	Miami	Florida
United States	American Research Corporation	San Antonio	Texas
United States	Harborview Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 to be < 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.	Post-treatment follow-up Week 12	No
Primary	Percentage of 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 to be < 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.	Post-treatment follow-up Week 12	No
Secondary	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 to be < 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.	Post-treatment follow-up Week 12	No
Secondary	Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels to be < 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 12	Participants who responded to treatment were assessed using proportion of subjects with hepatitis C Virus RNA levels to be < lower limit of quantitation i.e., 25 IU/mL target detected or target not detected, at each visit.	Week 1, 2, 4, 6, 8, 12, End of treatment, Follow-up Week 4, 8, and 12	No
Secondary	Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels to be < 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 to be < lower limit of quantitation i.e., 25 IU/mL target not detected, at each on-treatment visit.	Week 1, 2, 4, 6, 8, 12, End of treatment	No
Secondary	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	Week 12 (Follow-up period)	No
Secondary	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 Who Died During Treatment Period	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not has 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.	From start of study treatment up to 7 days post last dose of study treatment	Yes
Secondary	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.	From start of study treatment up to 7 days post last dose of study treatment	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry form