Clinical Trial Results:
A Phase III open-label study to evaluate the safety, tolerability and efficacy of TMC435 plus PegIFNα-2a (Pegasys®) and ribavirin (Copegus®) triple therapy in chronic hepatitis C genotype-1 infected subjects who are co-infected with Human Immunodeficiency Virus type 1 (HIV-1).
Due to a system error, the data reported in v1 is not correct and has been removed from public view.
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Summary
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EudraCT number |
2010-021337-31 |
Trial protocol |
GB ES PT |
Global end of trial date |
28 Aug 2013
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Results information
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Results version number |
v2(current) |
This version publication date |
30 Jun 2016
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First version publication date |
31 Jul 2015
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Other versions |
v1 (removed from public view) |
Version creation reason |
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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 |
TMC435-TiDP16-C212
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01479868 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen Sciences 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 Sciences Ireland, 353 21 4673500, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen Sciences Ireland, 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 |
28 Aug 2013
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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 |
28 Aug 2013
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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 |
To evaluate the safety and tolerability of TMC435 plus pegylated interferon alpha-2a (PegIFNα- 2a) and ribavirin (RBV) triple therapy in hepatitis C virus (HCV) genotype-1 infected participants, co-infected with human immunodeficiency virus- 1 (HIV-1).
To evaluate the proportion of participants with sustained virologic response (SVR) 12 weeks after the planned end of treatment (SVR12).
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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, measurement of vital signs, electrocardiogram (ECG) and performing physical examinations throughout the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Sep 2011
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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 |
Canada: 8
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Country: Number of subjects enrolled |
Germany: 17
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Country: Number of subjects enrolled |
Spain: 11
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Country: Number of subjects enrolled |
France: 8
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Country: Number of subjects enrolled |
United Kingdom: 9
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Country: Number of subjects enrolled |
Portugal: 12
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Country: Number of subjects enrolled |
United States: 41
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Worldwide total number of subjects |
106
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EEA total number of subjects |
57
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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) |
104
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 160 participants were screened, 107 were enrolled of whom 106 participants received at least 1 dose of study drug. | ||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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TMC435 150mg 12Wks PR24/48 | ||||||||||||||||||||
Arm description |
Participants On HAART (n=93) and Not on HAART (n=13) were given 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-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), Participants with cirrhosis, and HCV treatment-naïve 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 |
JNJ-38733214-AAA - capsule , hard - 150mg
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Investigational medicinal product code |
TMC435
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered JNJ-38733214-AAA - capsule , hard 150 mg orally, once daily.
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Investigational medicinal product name |
Pegasys
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Investigational medicinal product code |
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Other name |
PEGINTERFERON ALFA-2A
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants were administered PEGINTERFERON ALFA-2A (PegIFNα-2a) 180 microgram(s)/millilitre (µg/ml) once weekly as subcutaneous injection of 0.5 mL.
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Investigational medicinal product name |
Copegus
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Investigational medicinal product code |
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Other name |
Ribavirin
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were administered Ribavirin 1000 or 1200 milligrams (mg) orally, twice a day.
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Baseline characteristics reporting groups
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Reporting group title |
TMC435 150mg 12Wks PR24/48
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Reporting group description |
Participants On HAART (n=93) and Not on HAART (n=13) were given 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-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), Participants with cirrhosis, and HCV treatment-naïve 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 |
TMC435 150mg 12Wks PR24/48
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Reporting group description |
Participants On HAART (n=93) and Not on HAART (n=13) were given 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-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), Participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period. | ||
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End point title |
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) [1] | ||||||||
End point description |
The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per millilitre (IU/mL) undetectable at the planned end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment.
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End point type |
Primary
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End point timeframe |
12 weeks after planned end of treatment (Week 24 or 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: Descriptive statistics were done, no inferential statistical analyses were performed |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) | ||||||||
End point description |
The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per millilitre (IU/mL) undetectable at the planned end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment.
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End point type |
Secondary
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End point timeframe |
24 weeks after planned end of treatment (Week 24 or 48).
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| No statistical analyses for this end point | |||||||||
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End point title |
On treatment data for percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | ||||||||||||||||||||||||
End point description |
Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed. ITT population included all participants who had at least 1 dose of study drug. Here, "N" (number of participants analysed) is the number of participants analysed for this outcome measure, "n" is the number of participants analysed for this outcome measure at specific time points.
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End point type |
Secondary
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End point timeframe |
Week 4, 12, 24, 36, and 48
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of Participants With On-treatment 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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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Viral Breakthrough | ||||||||
End point description |
Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy.
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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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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Viral Relapse | ||||||||
End point description |
Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL. The incidence of viral relapse is only calculated for subjects with undetectable (or unconfirmed detectable) HCV RNA levels at actual end of treatment, 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) up to end of follow-up period
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Normalized Alanine Aminotransferase Levels | ||||||||
End point description |
Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of normal range at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure | ||||||||||||
End point description |
Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL for participants on HAART (n=93).
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End point type |
Secondary
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End point timeframe |
Baseline to Week 72.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | ||||||||||||||||||||||||||||||||||||||||
End point description |
Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here "n" signifies participants evaluable for this measure at specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Mean Change From Baseline in CD4+ Cell Count | ||||||||||||||||||||||||||||||||||||||||
End point description |
Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here, "n" is the number of participants analysed for this outcome measure at specific time points for participants on HAART (n=93).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline in CD4+ Cell Count in Percentage | ||||||||||||||||||||||||||||||||||||||||
End point description |
Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analysed. Here, "n" is the number of participants analysed for this outcome measure at specific time points for participants on HAART (n=93).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | ||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state.
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End point type |
Secondary
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End point timeframe |
Baseline up to End of Treatment (EOT: Week 24 or Week 48 or Early Withdrawal) +4 weeks.
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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) +4 weeks.
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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 |
TMC435 150mg 12Wks PR24/48
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Reporting group description |
Participants On HAART (n=93) and Not on HAART (n=13) were given 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-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), subjects with cirrhosis, and HCV treatment-naïve 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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19 Jan 2012 |
The amendment was created to implement the changes to the protocol based on the feedback from the Health Authorities, mainly on primary efficacy endpoint for ongoing and future TMC435 Phase III trials could be changed from SVR24 to SVR12. SVR24 became a secondary endpoint. |
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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 | |||
