- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00665847
TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents
April 2, 2015 updated by: Tibotec Pharmaceuticals, Ireland
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
The purpose of this study is to determine the safety and antiviral activity of etravirine in treatment-experienced human immunodeficiency virus (HIV) infected children and adolescents.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The study design is a single arm treatment (all patients assigned to receive etravirine), open label (patients will know the identity of the treatments they are receiving) safety and antiviral activity of Etravirine (TMC125) in treatment-experienced, HIV infected children and adolescents 6 to 17 years of age.
Etravirine is a new drug belonging to the NNRTI (a non-nucleoside reverse transcriptase inhibitor) drug class that slows down the growth of the human immunodeficiency virus (HIV).
This drug has been tested for safety and effectiveness in adults, however, there is no data on the drug's long-term safety and antiviral activity in children and adolescents.
This study will last for a maximum of 48 weeks.
A total of 100 ptients will receive etravirine tablets based on body weight and an investigator selected optimized background regimen (OBR) of at least 2 antiretrovirals (ARVs), consisting of a boosted protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor(s) (NRTI[s]).
Use of enfuvirtide is optional.
Safety will be monitored throughout the study.
Study Type
Interventional
Enrollment (Actual)
103
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Buenos Aires, Argentina
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Belo Horizonte, Brazil
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Ribeirao Preto, Brazil
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Rio De Janeiro, Brazil
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Ontario
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Quebec
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Montreal, Quebec, Canada
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Lyon Cedex 08, France
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Nantes Cedex 1, France
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Paris, France
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Toulouse Cedex 3 N/A, France
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Amsterdam Zuidoost, Netherlands
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Almada, Portugal
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Lisboa, Portugal
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Porto, Portugal
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Rio Piedras, Puerto Rico
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San Juan, Puerto Rico
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Bucuresti, Romania
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Constanta, Romania
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Dundee, South Africa
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Durban, South Africa
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Port Elizabeth, South Africa
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Barcelona, Spain
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Esplugues De Llobregat, Spain
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Madrid, Spain
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Sevilla, Spain
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Bangkok, Thailand
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Khon Kaen, Thailand
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Birmingham, United Kingdom
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Alabama
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Mobile, Alabama, United States
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California
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Los Angeles, California, United States
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District of Columbia
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Washington, District of Columbia, United States
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Louisiana
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New Orleans, Louisiana, United States
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Missouri
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Saint Louis, Missouri, United States
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New Jersey
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New Brunswick, New Jersey, United States
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New York
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Bronx, New York, United States
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New York, New York, United States
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Syracuse, New York, United States
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Pennsylvania
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Philadelphia, Pennsylvania, United States
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Tennessee
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Memphis, Tennessee, United States
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Texas
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Dallas, Texas, United States
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Fort Worth, Texas, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- HIV-1 infected
- Body weight according to age within the 10-90th percentile of CDC growth chart
- On steady antiretroviral therapy regimen for at least 8 weeks at screening and willing to remain on that regimen until baseline
- HIV viral load of 1,000 copies/ml or greater at study entry
- Parent or legal guardian willing to provide informed consent, if necessary
Exclusion Criteria:
- The Key Exclusion Criteria are: Evidence of resistance to etravirinel Any grade 3 or 4 toxicity (More information available in the protocol)
- Use of disallowed concomitant therapy (specified in the protocol)
- Currently active AIDS defining illness (category C)
- Active hepatitis A, B or C virus infection
- Any clinically significant diseases or findings that, in the opinion of the investigator, would interfere with the study
- Receipt of any ARV or non-ARV investigational medication or investigational vaccine within 30 days prior to screening
- History of clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC125)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Etravirine (TMC125)
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Patients will be dosed by body weight , i.e. 5.2 mg/kg twice daily (b.i.d.) up to a maximum of 200 mg b.i.d. for 48 weeks.
An investigator-selected optimized background regimen (OBR) comprising of a low-dose ritonavir (rtv)-boosted protease inhibitor (PI) (either lopinavir [LPV], darunavir [DRV], atazanavir [ATV] or saquinavir [SQV]) in combination with nucleos(t)ide reverse transcriptase inhibitor(s) (N[t]RTIs) to be dosed according to the drugs individual package inserts for 48 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Time Frame: 48 weeks
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A treatment-emergent adverse event (TEAE) was 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.
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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48 weeks
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The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
Time Frame: 48 weeks
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The percentage of patients 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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48 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h)
Time Frame: Weeks 4-48
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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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Weeks 4-48
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Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)
Time Frame: Week 48
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Week 48
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Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax)
Time Frame: Week 4
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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 as shown in the table below.
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Week 4
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Percentage of Patients With Virologic Response at Week 24
Time Frame: Week 24
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Virologic response was defined as the percentage of patients with plasma viral load < 50 copies/mL at Week 24 calculated according to the non-completer=failure (NC=F) imputation method.
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Week 24
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Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time
Time Frame: Baseline, Week 48
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Baseline, Week 48
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The Change From Baseline in CD4 Cell Counts Over Time
Time Frame: Baseline, Week 48
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Baseline, Week 48
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The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
Time Frame: Baseline and Endpoint (up to Week 48)
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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 > 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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Baseline and Endpoint (up to Week 48)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2008
Primary Completion (Actual)
May 1, 2011
Study Completion (Actual)
August 1, 2011
Study Registration Dates
First Submitted
April 22, 2008
First Submitted That Met QC Criteria
April 23, 2008
First Posted (Estimate)
April 24, 2008
Study Record Updates
Last Update Posted (Estimate)
April 23, 2015
Last Update Submitted That Met QC Criteria
April 2, 2015
Last Verified
April 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR002746
- TMC125-TiDP35-C213 (Other Identifier: Tibotec Pharmaceuticals, Ireland)
- 2007-007086-21 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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