A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation

NCT ID: NCT01938625

Last Updated: 2018-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-12
• Study Completion Date: 2015-07-28

Brief Summary

The purpose of the study is to evaluate effect of steady-state (when the amount of drug administered (in a given time period is equal to the amount of drug eliminated in that same period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication does to the body) of cyclosporine (applicable to Part 1 only) and tacrolimus when administered as a combinational regimen in post-orthotopic liver transplantation (OLT) participants with recurrent hepatitis C virus (HCV) genotype 1b infection and effectiveness of a 24-week treatment regimen containing simeprevir, daclatasvir, and ribavirin (RBV) with respect to the proportion of HCV genotype 1b infected post-OLT participants achieving sustained virologic response 12 weeks after end of treatment.

Detailed Description

This is an open-label (all participants of this study know the identity of the intervention) and multicenter (study conducted at multiple sites) study. This study will be conducted in 2 parts. Both the parts of the study will consist of screening phase (4 weeks), treatment period (24 weeks), and a post-treatment follow-up (24 weeks). A total of 30 participants will be enrolled in Part 1 and Part 2 of the study. A minimum of 9 participants were planned to receive cyclosporine as stable immunosuppressant therapy and a minimum of 9 participants were planned to receive tacrolimus as stable immunosuppressant therapy during Part 1. All participants will be receiving tacrolimus as stable immunosuppressant therapy during Part 2. In Part 1 of the study, participants with Metavir score of F1-F2, will receive a combination of study drugs - simeprevir, daclatasvir, and ribavirin for 24 weeks. In Part 2 of the study, participants with Metavir score F1-F4 will receive a dosing regimen of study drugs based on the data from Part 1 of the study. Safety evaluations will include assessments of adverse events, clinical laboratory tests, urinalysis, electrocardiogram, vital signs, and physical examination. The total study duration for each participant will be approximately 52 weeks.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1

Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.

Group Type: EXPERIMENTAL

Simeprevir

Intervention Type: DRUG

Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.

Daclatasvir

Intervention Type: DRUG

Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.

Ribavirin

Intervention Type: DRUG

Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.

Cyclosporine

Intervention Type: DRUG

Participants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks.

Tacrolimus

Intervention Type: DRUG

Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.

Part 2

Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy.

Group Type: EXPERIMENTAL

Simeprevir

Intervention Type: DRUG

Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.

Daclatasvir

Intervention Type: DRUG

Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.

Ribavirin

Intervention Type: DRUG

Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.

Tacrolimus

Intervention Type: DRUG

Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.

Interventions

Simeprevir

Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.

Intervention Type: DRUG

Daclatasvir

Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.

Intervention Type: DRUG

Ribavirin

Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.

Intervention Type: DRUG

Cyclosporine

Participants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks.

Intervention Type: DRUG

Tacrolimus

Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Liver transplant between 6 months and 10 years prior to the screening visit
• Hepatitis C virus (HCV) genotype 1 subtype b infection confirmed at screening
• Screening HCV ribonucleic acid level greater than 10,000 IU/mL
• HCV treatment-naïve participants must not have received post orthotopic liver transplant treatment with any approved or investigational drug for the treatment of HCV
• Receiving stable immunosuppressant therapy (ie, no change in dose in the last month) with cyclosporine (only allowed in Part 1) or tacrolimus for more than 3 months prior to the screening visit

Exclusion Criteria

• Evidence of acute or chronic hepatic decompensation after the liver transplantation (including ascites, bleeding varices or hepatic encephalopathy)
• Any liver disease of non-HCV etiology, including current evidence of graft rejection except the presence of liver steatosis
• Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of ribavirin
• Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B surface antigen positive)
• Multi-organ transplant that included heart, lung, pancreas, or kidney

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen R&D Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen R&D Ireland Clinical Trial

Role: STUDY_DIRECTOR

Janssen R&D Ireland

Locations

Essen, , Germany

Hamburg, , Germany

Warsaw, , Poland

Barcelona, , Spain

Madrid, , Spain

Valencia, , Spain

Countries

Germany; Poland; Spain

References

Forns X, Berenguer M, Herzer K, Sterneck M, Donato MF, Andreone P, Fagiuoli S, Cieciura T, Durlik M, Calleja JL, Marino Z, Shukla U, Verbinnen T, Lenz O, Ouwerkerk-Mahadevan S, Peeters M, Janssen K, Kalmeijer R, Jessner W. Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver transplantation: The Phase II SATURN study. Transpl Infect Dis. 2017 Jun;19(3). doi: 10.1111/tid.12696. Epub 2017 May 4.

Reference Type: DERIVED

PMID: 28295849 (View on PubMed)

Other Identifiers

TMC435HPC3016

Identifier Type: OTHER

Identifier Source: secondary_id

2013-002726-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR102639

Identifier Type: -

Identifier Source: org_study_id