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Completed

NCT Number: 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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Essen, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Daclatasvir

Drug

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

Ribavirin

Drug

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

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.

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.

Primary outcomes

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

    Time frame: Week 36

    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.

Secondary outcomes

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

    Time frame: Week 28

    Participants were considered to have achieved SVR4 if HCV RNA levels were (<) 25 IU/mL detectable or undetectable at 4 weeks after the end of treatment.

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

    Time frame: Week 48

    Participants were considered to have achieved SVR 24 if hepatitis C virus ribonucleic acid (HCV RNA) levels were (<) 25 IU/mL detectable or undetectable at 24 weeks after the end of treatment.

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

    Time frame: Weeks 2, 4, 12, and 24

    Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.

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

    Time frame: Week 4

    Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported.

  5. Number of Participants With On-Treatment Failure

    Time frame: Up to Week 24 after actual EOT (week 24)

    On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been <lower limit of quantification (LLOQ) while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to adverse events (AEs), withdrawal of consent).

  6. Number of Participants With Viral Breakthrough

    Time frame: Up to week 24

    Viral breakthrough is defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in participants whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment.

  7. Number of Participants With Viral Relapse

    Time frame: Up to Week 24 after actual EOT (week 24)

    Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.

Sponsors and collaborators

Lead sponsor

Janssen R&D Ireland

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Sep 10, 2013
Registry last updated
Nov 21, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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