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

Tibotec Pharmaceuticals, Ireland103 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

103

Conditions

HIV-1

Interventions

Etravirine (TMC125)DRUG

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.

Optimized background regimen (OBR)DRUG

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.

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

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)

Locations (42)

Outcomes

Primary Outcomes

The Number of Patients With Treatment-emergent Adverse Events (TEAEs)

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

Time frame: 48 weeks

The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)

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

Time frame: 48 weeks

Secondary Outcomes

Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h)

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.

Time frame: Weeks 4-48

Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)

Time frame: Week 48

Data from ClinicalTrials.gov

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