Clinical Trial Results:
An Open-Label, Single-Arm Phase III Study to Evaluate the Efficacy, Safety and Tolerability of TMC435 in Combination With PegIFN alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naive or Treatment-Experienced, Chronic Hepatitis C Virus Genotype-4 Infected participants.
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Summary
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EudraCT number |
2011-004097-29 |
Trial protocol |
BE |
Global end of trial date |
20 Mar 2014
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Results information
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Results version number |
v1 |
This version publication date |
06 Jul 2016
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First version publication date |
20 Jun 2015
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TMC435HPC3011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01567735 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen R&D Ireland
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Sponsor organisation address |
Eastgate Village,Eastgate, Little Island, Co. Cork, Ireland,
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Public contact |
Clinical Registry Group, Janssen Research & Development, +353 21 4673500, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Research & Development, +353 21 4673500, ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Mar 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Mar 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective is to evaluate the efficacy of TMC435 in combination with PegIFNα-2a/RBV with respect to the proportion of participants with chronic HCV-4 infection achieving SVR 12 weeks after planned end of treatment (SVR12) in the overall population as well as in the different subpopulations (treatment-naive, previous relapsers and previous nonresponders).
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Protection of trial subjects |
Safety and tolerability were evaluated throughout the study by monitoring of adverse events (AEs), performing laboratory tests, monitoring of adverse events (AEs),measurement of vital signs, electrocardiogram and performing physical examinations.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
16 Feb 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 38
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Country: Number of subjects enrolled |
France: 69
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Worldwide total number of subjects |
107
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EEA total number of subjects |
107
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
100
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted from 16 February 2012 to 20 March 2014. | ||||||||||||
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Pre-assignment
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Screening details |
136 participants were screened of whom 107 participants were treated and 103 participants completed the study. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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simeprevir (TMC435) | ||||||||||||
Arm description |
Participants received TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naive and prior HCV relapsers who met the response guided therapy criteria. All prior HCV non-responders (null and partial), and HCV treatment-naive and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
simeprevir
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Investigational medicinal product code |
TMC435
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naive and prior HCV relapsers who met the response guided therapy criteria. All prior HCV non-responders (null and partial), and HCV treatment-naive and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
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Baseline characteristics reporting groups
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Reporting group title |
simeprevir (TMC435)
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Reporting group description |
Participants received TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naive and prior HCV relapsers who met the response guided therapy criteria. All prior HCV non-responders (null and partial), and HCV treatment-naive and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
simeprevir (TMC435)
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Reporting group description |
Participants received TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naive and prior HCV relapsers who met the response guided therapy criteria. All prior HCV non-responders (null and partial), and HCV treatment-naive and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period. | ||
Subject analysis set title |
Intent-to-treat (ITT) population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Intent-to-treat (ITT) population, which includes all participants who took at least 1 dose of study medication.
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End point title |
Percentage of participants achieving sustained virologic response 12 weeks after planned end of treatment (SVR12) [1] | ||||||||||||||||
End point description |
Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (<) 25 International unit per milliliter (IU/mL) undetectable at the actual end of treatment; 2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable 12 weeks after planned end of treatment. SVR 12 was reported for overall population (that is, ITT population), treatment naive, relapser and non-responder participants. 'N' (number of participants analyzed) signifies the participants evaluable for this measure and "n" signifies those participants who were evaluated for this measure at the specified time point.
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End point type |
Primary
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End point timeframe |
12 Weeks After the Planned End of Treatment (Planned EOT: if participant eligible for response-guided treatment (RGT) and met the criteria: Week 24; otherwise Week 48)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not reported for this endpoint as inferential analysis was not performed as planned. |
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| Notes [2] - ITT Population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of participants achieving sustained virologic response 4 weeks after planned end of treatment (SVR4) | ||||||||
End point description |
Participants are considered to have reached SVR4 and SVR 12 if both conditions below are met: 1) HCV RNA levels less than <25 International unit per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable (4, 12, 24, 36 and 48 weeks after the planned EOT).
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End point type |
Secondary
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End point timeframe |
4 weeks after Planned EOT (if participant eligible for response-guided treatment (RGT) and met the criteria: Week 24; otherwise Week 48)
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| Notes [3] - ITT Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants achieving sustained virologic response 24 weeks after planned end of treatment (SVR24). | ||||||||
End point description |
Participants are considered to have reached SVR24 if both conditions below are met: 1) HCV RNA levels less than <25 International units per milliliter (IU/mL) undetectable (at the actual end of treatment);2) HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable (24 weeks after the planned EOT.
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End point type |
Secondary
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End point timeframe |
24 Weeks After the Planned EOT (if participant eligible for response-guided treatment (RGT) and met the criteria: Week 24; otherwise Week 48
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| Notes [4] - ITT Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With On-treatment Virologic Failure | ||||||||
End point description |
Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.
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End point type |
Secondary
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End point timeframe |
Actual EOT (Week 24 or Week 48 or Early withdrawal)
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| Notes [5] - ITT Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Viral Breakthrough | ||||||||
End point description |
Viral breakthrough was defined as a confirmed increase of more than 1 log10 in Hepatitis C Virus (HCV)
ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of HCV RNA more than
100 international units/milliliter (IU/mL) in participants whose HCV RNA was previously less than 25
IU/mL.
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End point type |
Secondary
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End point timeframe |
Up to Actual EOT (Week 24 or Week 48 or Early withdrawal)
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| Notes [6] - ITT Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Viral Relapse | ||||||||
End point description |
Participants are considered to have a viral relapse if both conditions as specified are met: 1) <25 IU/mL undetectable HCV RNA at the actual end of study drug treatment; 2) confirmed HCV RNA greater than or equal to (>=) 25 IU/mL during follow-up. ‘N’ (number of participants analyzed) signifies those participants who were evaluable for this measure. The incidence of viral relapse is only calculated for subjects with undetectable HCV RNA levels (or unconfirmed detectable) at EOT and with at least one follow-up HCV RNA measurement.
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End point type |
Secondary
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End point timeframe |
Actual EOT (Week 24 or Week 48 or Early withdrawal) upto end of follow up period
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | ||||||||||||
End point description |
An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
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End point type |
Secondary
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End point timeframe |
Upto End of treatment (EOT:week 48)
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| Notes [7] - ITT Population |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to End of Treatment (EOT: Week 24 or Week 48 or Early Withdrawal)
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Adverse event reporting additional description |
Adverse events were reported for the entire treatment phase.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
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Reporting groups
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Reporting group title |
Simeprevir(TMC435)
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Reporting group description |
Participants received TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naive and prior HCV relapsers who met the response guided therapy criteria. All prior HCV non-responders (null and partial), and HCV treatment-naive and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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22 Feb 2012 |
Based on consultations with Health Authorities, the following substantial changes:
The definitions for SVR12 and SVR24 were evaluated and updated and it clarified that a liver biopsy is the required method for all subjects without a contraindication for this procedure. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
