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TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents

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ClinicalTrials.gov Identifier: NCT00665847
Recruitment Status : Completed
First Posted : April 24, 2008
Results First Posted : December 21, 2012
Last Update Posted : April 23, 2015
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HIV-1 Drug: Etravirine (TMC125) Drug: Optimized background regimen (OBR) Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : November 2008
Actual Primary Completion Date : May 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Etravirine
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Etravirine (TMC125) Drug: Etravirine (TMC125)
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.
Drug: Optimized background regimen (OBR)
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.


Outcome Measures
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Primary Outcome Measures :
  1. The Number of Patients With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 48 weeks ]
    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

  2. The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 48 weeks ]
    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


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h) [ Time Frame: Week 48 ]
  3. Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax) [ Time Frame: Week 4 ]
    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.

  4. Percentage of Patients With Virologic Response at Week 24 [ Time Frame: Week 24 ]
    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.

  5. Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time [ Time Frame: Baseline, Week 48 ]
  6. The Change From Baseline in CD4 Cell Counts Over Time [ Time Frame: Baseline, Week 48 ]
  7. 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) ]
    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).


Eligibility Criteria
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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00665847


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Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00665847     History of Changes
Obsolete Identifiers: NCT00750542
Other Study ID Numbers: CR002746
TMC125-TiDP35-C213 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
2007-007086-21 ( EudraCT Number )
First Posted: April 24, 2008    Key Record Dates
Results First Posted: December 21, 2012
Last Update Posted: April 23, 2015
Last Verified: April 2015

Keywords provided by Tibotec Pharmaceuticals, Ireland:
HIV-1
TMC125-TiDP35-C213
TMC125-C213

Additional relevant MeSH terms:
Antiviral Agents
Etravirine
Anti-Infective Agents
Reverse Transcriptase Inhibitors
 Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents