Clinical Trial Results:
A Phase II, open-label trial to evaluate the safety, tolerability and antiviral activity of TMC125 in antiretroviral experienced HIV-1 infected children and adolescents
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Summary
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EudraCT number |
2007-007086-21 |
Trial protocol |
GB DE BE PT ES FR NL IT |
Global end of trial date |
30 Aug 2011
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Results information
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Results version number |
v2(current) |
This version publication date |
23 Jun 2016
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First version publication date |
16 May 2015
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Other versions |
v1 |
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 |
TMC125-TiDP35-C213
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00665847 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Tibotec Pharmaceuticals
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Sponsor organisation address |
Eastgate Village, Eastgate, Little Island, Co Cork, Ireland,
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Public contact |
Tibotec Pharmaceuticals, Clinical Registry Group, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Tibotec Pharmaceuticals, Clinical Registry Group, 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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000222-PIP01-08 | ||
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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Aug 2011
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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 |
30 Aug 2011
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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 safety and tolerability of etravirine in combination with other antiretroviral (ARVs) over a 24-week treatment period in children and adolescents.
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Protection of trial subjects |
The safety assessments included laboratory measurements (for example hematology and coagulation, biochemistry, urinalysis, hepatitis serology/Viremia), cardiovascular safety, vital sign measurements and electrocardiograms (ECGs). Adverse events and vital signs were monitored throughout the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Aug 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Argentina: 15
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Country: Number of subjects enrolled |
Brazil: 9
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Country: Number of subjects enrolled |
Canada: 4
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Puerto Rico: 1
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Country: Number of subjects enrolled |
Portugal: 5
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Country: Number of subjects enrolled |
Romania: 4
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Country: Number of subjects enrolled |
Thailand: 20
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Country: Number of subjects enrolled |
United States: 15
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Country: Number of subjects enrolled |
South Africa: 10
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Worldwide total number of subjects |
101
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EEA total number of subjects |
27
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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) |
41
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Adolescents (12-17 years) |
60
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
In total, 41 investigators in 13 countries enrolled participants in study TMC125-C213. | ||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 103 participants were documented as being enrolled in the study. Among those, 101 participants were treated with etravirine (ETR) also known as TMC125 and were included in the intent-to-treat (ITT) population. | ||||||||||||||||||||||
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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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TMC125 | ||||||||||||||||||||||
Arm description |
TMC125 dosed according to body weight (kilogram) from 100 milligram (mg) to 200 mg twice a day | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
TMC125
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Investigational medicinal product code |
TMC125 (formulation F060 and F066)
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
TMC125 dosed according to body weight (kilogram) from 100 milligram (mg) to 200 mg twice a day
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Baseline characteristics reporting groups
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Reporting group title |
TMC125
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Reporting group description |
TMC125 dosed according to body weight (kilogram) from 100 milligram (mg) to 200 mg twice a day | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
TMC125
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Reporting group description |
TMC125 dosed according to body weight (kilogram) from 100 milligram (mg) to 200 mg twice a day | ||
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End point title |
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The percentage of participants with a treatment-emergent adverse event (TEAE) (defined as an event that occurred in the 48-week treatment period during which it emerged [i.e. started or worsened in severity, relation, or other attribute], and not in the subsequent study periods, even if the event continued to be present] are provided below. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen.
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End point type |
Primary
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End point timeframe |
48 weeks
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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 |
Area Under the Plasma Concentration-Time Curve Over 12 Hours at Steady-state (AUC12h) of Etravirine | ||||||||
End point description |
The AUC12h is a Bayesian estimation based on a population pharmacokinetic model and sparse samples collected at each visit over the duration of trial. For each sparse sample taken, the time blood sample was recorded as well as the time of etravirine intake just prior to the time of blood sample.
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End point type |
Secondary
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End point timeframe |
Weeks 4-48
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| No statistical analyses for this end point | |||||||||
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End point title |
Trough Plasma Concentration (C0h) of Etravirine | ||||||||
End point description |
Trough plasma concentration is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose.
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End point type |
Secondary
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End point timeframe |
Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Plasma Concentration (Cmax) of Etravirine | ||||||||
End point description |
Etravirine/TMC125 (ETR) Cmax was approximated for each individual using the median value of plasma ETR concentrations taken 4 hours postdose (± 1 hour), when available, on the day of the Week 4 visit.
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End point type |
Secondary
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End point timeframe |
Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With Virologic Response at Week 24 | ||||||||
End point description |
Virologic response was defined as the percentage of participants with plasma viral load less than (< ) 50 copies/ milliliter (mL) at Week 24 calculated according to the non-completer=failure (NC=F) imputation method.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Human Immunodeficiency Virus – Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time | ||||||||
End point description |
Human Immunodeficiency Virus – Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Cell Counts Over Time | ||||||||
End point description |
CD4 cells (a type of white blood cells) are circulating in blood and gives an idea of how strong the HIV positive person's immune system really is. The values of CD4 cell counts were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
The Emergence of Non-Nucleoside Reverse Transcriptase Inhibitor Resistance-Associated Mutations (NNRTI RAMs) in Participants Classified as Virologic Failures | ||||||||||||||
End point description |
Virologic failure (lack of response) was defined as: plasma viral load decline of < 0.5 log10 from Baseline by Week 8 and/or plasma viral load decline of <1.0 log10 from Baseline by Week 12. Virologic failure (loss of response) was defined as 2 consecutive measurements of plasma viral load greater than (>) 0.5 log10 above the nadir after a minimum of 12 weeks of treatment. The table below provides data for 41 viologic failures of which 30 had mutation data available. In the table below, only the 4 most frequently emerging mutations are presented (emerging in at least 3 patients).
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End point type |
Secondary
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End point timeframe |
Baseline and Endpoint (up to Week 48)
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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 |
Up to Week 52
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Adverse event reporting additional description |
Only participants who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. participants with Non-Serious Adverse Events.
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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 |
11.1
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Reporting groups
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Reporting group title |
TMC125
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Reporting group description |
TMC125 dosed according to body weight (kilogram) from 100 milligram (mg) to 200 mg twice a day | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Sep 2008 |
The overall reason for the amendment was to address feedback provided by the United States Food and Drug Administration (US FDA) and modify inclusion criterion. |
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30 Jan 2009 |
The overall reason for the amendment was to modify inclusion criterion. |
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24 Mar 2010 |
The overall reason for the amendment was to adjust body weight criterion, definition Serious Adverse Events (SAE) and criterion regarding co-enrollment of participants in another study. |
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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 | |||
