Clinical trial NCT00352053: Safety and Efficacy of Tenofovir DF in HIV-1 Infected Adolescents Failing Their Current Antiretroviral Therapy
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Tenofovir DF as Part of an Optimized Antiretroviral Regimen in HIV-1-Infected Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Phase 3
Randomized, Double-Blind
Control
Treatment-Experienced
OBR
Optimized background regimen
Highly Active Antiretroviral Therapy
HAART
HIV
HIV-1
AIDS Virus
Human Immunodeficiency Virus
Acquired Immune Deficiency Syndrome Virus
Virus
Human Immunodeficiency
Pediatrics
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2006-07-14
Enrollment: 87
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) plus a genotype-guided optimized background regimen (OBR) compared to placebo plus OBR in the treatment of human immunodeficiency virus type 1 (HIV-1) infected antiretroviral treatment-experienced adolescents with plasma HIV-1 ribonucleic acid (RNA) levels greater than or equal to 1000 copies/mL.

Detailed description: This is a 48-week, randomized, double-blind, placebo-controlled, multicenter study of the safety and efficacy of tenofovir DF as part of an optimized antiretroviral regimen in HIV-1 infected adolescents (12 years to \< 18 years of age) who are failing their current antiretroviral regimen and have HIV-1 RNA levels ≥ 1000 copies/mL at screening. Data from three consecutive 96-week study extensions have been used to evaluate the long-term efficacy, safety, and tolerability of open-label tenofovir DF as part of an antiviral regimen, providing data for up to 336 weeks of total drug exposure.

Pretreatment:

HIV-1 genotyping will be performed as part of the screening assessments to assist in the construction of an OBR, defined as at least 3, but no more than 5 antiretroviral agents, not including tenofovir DF or placebo.

Randomized Phase:

Participants will be randomized in a 1:1 ratio to receive either tenofovir DF + OBR, or placebo + OBR. The majority of efficacy and safety assessments will be performed at each clinic visit (Weeks 4, 8, 16, 24, 32, 40, and 48). At Week 24, participants who are adherent to study drug (in the opinion of the investigator), but do not demonstrate a ≥ 0.5 log10 copies/mL decrease from baseline in HIV-1 RNA, will be considered to be nonresponders and will be unblinded. Nonresponders randomized to the placebo group will be given the option to continue on study and receive open-label tenofovir DF with an appropriate background regimen determined by the investigator. Nonresponders randomized to the tenofovir DF treatment group will be discontinued from the study.

Extension Phases:

After completing 48 weeks of double-blind treatment with tenofovir DF or placebo, participants who have not reached 18 years of age, and who, in the opinion of the investigator, would derive clinical benefit from the use of open-label tenofovir DF, will be given the option to continue (or initiate) treatment with open-label tenofovir DF in the first of three 96 week study extension periods. Nonresponders who receive open-label tenofovir DF after Week 24 will also be considered eligible for the first study extension if they met the above criteria at Week 48.

After completing the first 96 week study extension, participants who have not reached 18 years of age, and who have shown ongoing clinical benefit from tenofovir DF, will be given the option to continue receiving open-label tenofovir DF for an additional 96 weeks or until tenofovir DF became commercially available in the country where the participants are enrolled, whichever occurs first.

After completing the second 96 week study extension, participants who have not reached 18 years of age, and who have shown ongoing clinical benefit from tenofovir DF, will be given the option to continue receiving open-label tenofovir DF for an additional 96 weeks or until tenofovir DF became commercially available in the country where the participants are enrolled, whichever occurs first.

Presentation of data:

After the randomized phase of the study, participants randomized to placebo during the randomized phase of the study and then switch to open-label tenofovir DF will have their baseline reset (defined as open-label baseline), and only outcome data collected after (on/after for adverse events (AEs)/concomitant medications) participants receive their first dose of open-label tenofovir DF will be included.

Eligibility criteria: Major Inclusion Criteria:

* Weight ≥ 35 kg
* Documented laboratory diagnosis of HIV infection
* Plasma HIV-1 RNA ≥ 1000 copies/mL
* Prior antiretroviral treatment experience with at least 2 antiretroviral drug classes
* Naive to tenofovir DF
* Absence of K65R mutation on genotypic testing

Exclusion Criteria:

* Patients requiring didanosine in background regimen
* Prior history of significant renal disease
* Prior history of significant bone disease

Primary outcomes:
measure: Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA
timeFrame: Baseline to 24 Weeks
Secondary outcomes:
measure: Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA
timeFrame: Baseline to 48 weeks
measure: Change From Baseline to Week 24 in HIV-1 RNA
timeFrame: Baseline to 24 weeks
measure: Change From Baseline to Week 48 in HIV-1 RNA
timeFrame: Baseline to 48 weeks
measure: Change From Baseline to Week 96 in HIV-1 RNA
timeFrame: Baseline to 96 weeks
measure: Change From Baseline to Week 144 in HIV-1 RNA
timeFrame: Baseline to 144 weeks
measure: Change From Baseline to Week 192 in HIV-1 RNA
timeFrame: Baseline to 192 weeks
measure: Change From Baseline to Week 240 in HIV-1 RNA
timeFrame: Baseline to 240 weeks
measure: Change From Baseline to Week 288 in HIV-1 RNA
timeFrame: Baseline to 288 weeks
measure: Change From Baseline to Week 336 in HIV-1 RNA
timeFrame: Baseline to 336 weeks
measure: Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count
timeFrame: Baseline to 24 weeks
measure: Change From Baseline to Week 48 in CD4 Count
timeFrame: Baseline to 48 weeks
measure: Change From Baseline to Week 96 in CD4 Count
timeFrame: Baseline to 96 weeks
measure: Change From Baseline to Week 144 in CD4 Count
timeFrame: Baseline to 144 weeks
measure: Change From Baseline to Week 192 in CD4 Count
timeFrame: Baseline to 192 weeks
measure: Change From Baseline to Week 240 in CD4 Count
timeFrame: Baseline to 240 weeks
measure: Change From Baseline to Week 288 in CD4 Count
timeFrame: Baseline to 288 weeks
measure: Change From Baseline to Week 336 in CD4 Count
timeFrame: Baseline to 336 weeks
measure: Change From Baseline to Week 24 in CD4 Percentage
timeFrame: Baseline to 24 weeks
measure: Change From Baseline to Week 48 in CD4 Percentage
timeFrame: Baseline to 48 weeks
measure: Change From Baseline to Week 96 in CD4 Percentage
timeFrame: Baseline to 96 weeks
measure: Change From Baseline to Week 144 in CD4 Percentage
timeFrame: Baseline to 144 weeks
measure: Change From Baseline to Week 192 in CD4 Percentage
timeFrame: Baseline to 192 weeks
measure: Change From Baseline to Week 240 in CD4 Percentage
timeFrame: Baseline to 240 weeks
measure: Change From Baseline to Week 288 in CD4 Percentage
timeFrame: Baseline to 288 weeks
measure: Change From Baseline to Week 336 in CD4 Percentage
timeFrame: Baseline to 336 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24
timeFrame: Baseline to 24 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48
timeFrame: Baseline to 48 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96
timeFrame: Baseline to 96 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144
timeFrame: Baseline to 144 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192
timeFrame: Baseline to 192 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240
timeFrame: Baseline to 240 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288
timeFrame: Baseline to 288 weeks
measure: Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336
timeFrame: Baseline to 336 weeks
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192
timeFrame: Week 192
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240
timeFrame: Week 240
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288
timeFrame: Week 288
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336
timeFrame: Week 336
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144
timeFrame: Week 144
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192
timeFrame: Week 192
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240
timeFrame: Week 240
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288
timeFrame: Week 288
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336
timeFrame: Week 336
measure: Percentage of Participants With Virologic Failure Through Week 48
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Belo Horizonte - MG
country: Brazil
facility: Faculdade de Medicina - UFMG
city: Belo Horizonte - MG
country: Brazil
facility: Santa Casa de Belo Horizonte
city: Campinas - SP
country: Brazil
facility: Hospital e Maternidade Celso Pierro
city: Campinas - SP
country: Brazil
facility: Universidade Estadual de Campinas - UNICAMP
city: Campo Grande - MS
country: Brazil
facility: Centro de Doenças Infecciosas e Parasitárias
city: Curitiba - PR
country: Brazil
facility: Hospital das Clinicas da Universidade Federal do Parana - UFPR
city: Florianópolis - SC
country: Brazil
facility: Hospital Infantil Joana de Gusmão
city: Joinville - SC
country: Brazil
facility: Hospital Municipal Sao Jose
city: Recife
country: Brazil
facility: Hospital Materno Infantil Professor Fernando Figueira- IMIP
city: Rio de Janeiro
country: Brazil
facility: Hospital dos Servidores do Estado
city: Rio de Jeneiro
country: Brazil
facility: Hospital Geral de Nova Iguacu Ambulatorio de DST e AIDS
city: Santos
country: Brazil
facility: Hospital Guilherme Alvaro
city: Sao Paulo - SP
country: Brazil
facility: Instituto da Crianca do Hospital das Clinicas da FMUSP Depto de Pediatria
city: Sao Paulo - SP
country: Brazil
facility: Instituto de Infectologia Emilio Ribas
city: Sao Paulo
country: Brazil
facility: NEIMPE - Dept of Pediatrics Hospital das Clinicas FMRP-USP
city: Vila Clementino
country: Brazil
facility: Universidade Federal de Sao Paulo
city: Vitoria - ES
country: Brazil
facility: Hospital Infantil Nossa Senhora da Gloria Servico de Infectologia Pediatria
city: Panama City
country: Panama
facility: Hospital del Nino
Study officials:
affiliation: Gilead Sciences
name: Erin Quirk, MD
role: STUDY_DIRECTOR
References: