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

NCT01938625 | Completed Phase 2 Results

• 3 other identifiers: CR102639TMC435HPC30162013-002726-23
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 6

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.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C, Chronic; Recurrent Chronic Hepatitis C; Pharmacokinetics; Simeprevir; Daclatasvir; Ribavirin; Orthotopic Liver Transplantation; TMC435; BMS-790052; RBV

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)

  Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (\<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.

  Week 36

Secondary Outcomes (7)

• Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)

  Week 28

• Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)

  Week 48

• Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable

  Weeks 2, 4, 12, and 24

• Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4

  Week 4

• Number of Participants With On-Treatment Failure

  Up to Week 24 after actual EOT (week 24)

Study Arms (2)

Part 1

EXPERIMENTAL

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.

Drug: Simeprevir; Drug: Daclatasvir; Drug: Ribavirin; Drug: Cyclosporine; Drug: Tacrolimus

Part 2

EXPERIMENTAL

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.

Drug: Simeprevir; Drug: Daclatasvir; Drug: Ribavirin; Drug: Tacrolimus

Interventions

Simeprevir 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.

Part 1; Part 2

Daclatasvir DRUG

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

Part 1; Part 2

Ribavirin DRUG

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

Part 1; Part 2

Cyclosporine 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.

Part 1

Tacrolimus 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 1; Part 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen R&D Ireland: lead

Study Sites (6)

Unknown Facility

Essen, Germany

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Valencia, Spain

Location

Related Publications (1)

• 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.

  PMID: 28295849 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Simeprevir; daclatasvir; Ribavirin; Cyclosporine; Tacrolimus

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones

Results Point of Contact

• Title: Medical Leader
• Organization: Janssen Research & Development

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen R&D Ireland Clinical Trial

  Janssen R&D Ireland

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2013
• First Posted: September 10, 2013
• Study Start: December 12, 2013
• Primary Completion: April 27, 2015
• Study Completion: July 28, 2015
• Last Updated: November 21, 2018
• Results First Posted: November 21, 2018

Record last verified: 2018-11

Locations

DE (2); PL (1); ES (3)