Clinical trial NCT00665847: TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1
Keywords: HIV-1
TMC125-TiDP35-C213
TMC125-C213
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2008-04-24
Enrollment: 103
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 48 weeks
measure: The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 48 weeks
Secondary outcomes:
measure: Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h)
timeFrame: Weeks 4-48
measure: Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)
timeFrame: Week 48
measure: Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax)
timeFrame: Week 4
measure: Percentage of Patients With Virologic Response at Week 24
timeFrame: Week 24
measure: Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time
timeFrame: Baseline, Week 48
measure: The Change From Baseline in CD4 Cell Counts Over Time
timeFrame: Baseline, Week 48
measure: The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
timeFrame: Baseline and Endpoint (up to Week 48)
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: New Orleans
country: United States
state: Louisiana
city: Saint Louis
country: United States
state: Missouri
city: New Brunswick
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Memphis
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Belo Horizonte
country: Brazil
city: Ribeirao Preto
country: Brazil
city: Rio De Janeiro
country: Brazil
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Lyon Cedex 08
country: France
city: Nantes Cedex 1
country: France
city: Paris
country: France
city: Toulouse Cedex 3 N/A
country: France
city: Amsterdam Zuidoost
country: Netherlands
city: Almada
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Rio Piedras
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Bucuresti
country: Romania
city: Constanta
country: Romania
city: Dundee
country: South Africa
city: Durban
country: South Africa
city: Port Elizabeth
country: South Africa
city: Barcelona
country: Spain
city: Esplugues De Llobregat
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
city: Birmingham
country: United Kingdom
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Tambuyzer L, Thys K, Hoogstoel A, Nijs S, Tomaka F, Opsomer M, De Meyer S, Vingerhoets J. Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study. Antivir Ther. 2016;21(4):317-27. doi: 10.3851/IMP3011. Epub 2015 Nov 13.