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

NCT02032875 | Completed Phase 3 Results

• 1 other identifier: AI444-215
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 5

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  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

  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)

  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

  From start of study treatment up to 7 days post last dose of study treatment (approximately 13 weeks)

Study Arms (2)

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.

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

Drug: Daclatasvir; Drug: Sofosbuvir; Drug: Ribavirin

Interventions

Daclatasvir DRUG

Also known as: BMS-790052

Cirrhotic Cohort; Post-liver Transplant Cohort

Sofosbuvir DRUG

Cirrhotic Cohort; Post-liver Transplant Cohort

Ribavirin DRUG

Cirrhotic Cohort; Post-liver Transplant Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (5)

University Of Miami Schiff Center For Liver Diseases

Miami, Florida, 33136, United States

Location

University Of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Baylor St. Luke'S Medical Center

Houston, Texas, 77030, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis C

Interventions

daclatasvir; Sofosbuvir; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: January 10, 2014
• Study Start: March 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: January 1, 2016
• Last Updated: February 9, 2017
• Results First Posted: October 20, 2015

Record last verified: 2016-12

Locations

US (5)