Clinical trial NCT01938625: 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
Official title: Phase 2, Open-Label Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Tolerability of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052) and Ribavirin (RBV) in Subjects With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
Recurrent Chronic Hepatitis C
Pharmacokinetics
Simeprevir
Daclatasvir
Ribavirin
Orthotopic Liver Transplantation
TMC435
BMS-790052
RBV
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2013-09-10
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
timeFrame: Week 36
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
timeFrame: Week 28
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
timeFrame: Week 48
measure: Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
timeFrame: Weeks 2, 4, 12, and 24
measure: Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
timeFrame: Week 4
measure: Number of Participants With On-Treatment Failure
timeFrame: Up to Week 24 after actual EOT (week 24)
measure: Number of Participants With Viral Breakthrough
timeFrame: Up to week 24
measure: Number of Participants With Viral Relapse
timeFrame: Up to Week 24 after actual EOT (week 24)
Other outcomes:
Locations:
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Warszawa
country: Poland
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.