Back to resultsA 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
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Simeprevir
Daclatasvir
Ribavirin
Cyclosporine
Tacrolimus
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Hepatitis C, Chronic, Recurrent Chronic Hepatitis C, Pharmacokinetics, Simeprevir, Daclatasvir, Ribavirin, Orthotopic Liver Transplantation, TMC435, BMS-790052, RBV
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part 1
Part 2
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
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.
Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
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.
Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.
Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported.
Number of Participants With On-Treatment Failure
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).
Number of Participants With Viral Breakthrough
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.
Number of Participants With Viral Relapse
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.
Full Information
NCT ID
NCT01938625
First Posted
September 5, 2013
Last Updated
November 20, 2018
Sponsor
Janssen R&D Ireland
1. Study Identification
Unique Protocol Identification Number
NCT01938625
Brief Title
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
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
December 12, 2013 (Actual)
Primary Completion Date
April 27, 2015 (Actual)
Study Completion Date
July 28, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen R&D Ireland
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
Hepatitis C, Chronic, Recurrent Chronic Hepatitis C, Pharmacokinetics, Simeprevir, Daclatasvir, Ribavirin, Orthotopic Liver Transplantation, TMC435, BMS-790052, RBV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Simeprevir
Intervention Description
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
Intervention Name(s)
Daclatasvir
Intervention Description
Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Intervention Description
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
Intervention Name(s)
Tacrolimus
Intervention Description
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 Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
Description
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.
Time Frame
Week 36
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
Description
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.
Time Frame
Week 28
Title
Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
Description
Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.
Time Frame
Weeks 2, 4, 12, and 24
Title
Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
Description
Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported.
Time Frame
Week 4
Title
Number of Participants With On-Treatment Failure
Description
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).
Time Frame
Up to Week 24 after actual EOT (week 24)
Title
Number of Participants With Viral Breakthrough
Description
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.
Time Frame
Up to week 24
Title
Number of Participants With Viral Relapse
Description
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.
Time Frame
Up to Week 24 after actual EOT (week 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen R&D Ireland Clinical Trial
Organizational Affiliation
Janssen R&D Ireland
Official's Role
Study Director
Facility Information:
City
Essen
Country
Germany
City
Hamburg
Country
Germany
City
Warszawa
Country
Poland
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Valencia
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
28295849
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.
Results Reference
derived
Learn more about this trial
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
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