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Safety and Efficacy of Tenofovir DF in HIV-1 Infected Adolescents Failing Their Current Antiretroviral Therapy

Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Tenofovir DF (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Gilead Sciences

Official(s) and/or principal investigator(s):
Erin Quirk, MD, Study Director, Affiliation: Gilead Sciences

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA

Secondary outcome:

Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA

Change From Baseline to Week 24 in HIV-1 RNA

Change From Baseline to Week 48 in HIV-1 RNA

Change From Baseline to Week 96 in HIV-1 RNA

Change From Baseline to Week 144 in HIV-1 RNA

Change From Baseline to Week 192 in HIV-1 RNA

Change From Baseline to Week 240 in HIV-1 RNA

Change From Baseline to Week 288 in HIV-1 RNA

Change From Baseline to Week 336 in HIV-1 RNA

Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count

Change From Baseline to Week 48 in CD4 Count

Change From Baseline to Week 96 in CD4 Count

Change From Baseline to Week 144 in CD4 Count

Change From Baseline to Week 192 in CD4 Count

Change From Baseline to Week 240 in CD4 Count

Change From Baseline to Week 288 in CD4 Count

Change From Baseline to Week 336 in CD4 Count

Change From Baseline to Week 24 in CD4 Percentage

Change From Baseline to Week 48 in CD4 Percentage

Change From Baseline to Week 96 in CD4 Percentage

Change From Baseline to Week 144 in CD4 Percentage

Change From Baseline to Week 192 in CD4 Percentage

Change From Baseline to Week 240 in CD4 Percentage

Change From Baseline to Week 288 in CD4 Percentage

Change From Baseline to Week 336 in CD4 Percentage

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288

Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288

Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288

Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336

Percentage of Participants With Virologic Failure Through Week 48

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

Minimum age: 12 Years. Maximum age: 17 Years. Gender(s): Both.

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

Locations and Contacts

Faculdade de Medicina - UFMG, Belo Horizonte - MG, Brazil

Santa Casa de Belo Horizonte, Belo Horizonte - MG, Brazil

Hospital e Maternidade Celso Pierro, Campinas - SP, Brazil

Universidade Estadual de Campinas - UNICAMP, Campinas - SP, Brazil

Centro de Doenças Infecciosas e Parasitárias, Campo Grande - MS, Brazil

Hospital das Clinicas da Universidade Federal do Parana - UFPR, Curitiba - PR, Brazil

Hospital Infantil Joana de Gusmão, Florianópolis - SC, Brazil

Hospital Municipal Sao Jose, Joinville - SC, Brazil

Hospital Materno Infantil Professor Fernando Figueira- IMIP, Recife, Brazil

Hospital dos Servidores do Estado, Rio de Janeiro, Brazil

Hospital Geral de Nova Iguacu Ambulatorio de DST e AIDS, Rio de Jeneiro, Brazil

Hospital Guilherme Alvaro, Santos, Brazil

Instituto da Crianca do Hospital das Clinicas da FMUSP Depto de Pediatria, Sao Paulo - SP, Brazil

Instituto de Infectologia Emilio Ribas, Sao Paulo - SP, Brazil

NEIMPE - Dept of Pediatrics Hospital das Clinicas FMRP-USP, Sao Paulo, Brazil

Universidade Federal de Sao Paulo, Vila Clementino, Brazil

Hospital Infantil Nossa Senhora da Gloria Servico de Infectologia Pediatria, Vitoria - ES, Brazil

Hospital del Nino, Panama City, Panama

Additional Information

Starting date: June 2006
Last updated: June 15, 2015

Page last updated: August 23, 2015

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