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

NCT ID: NCT00352053

Last Updated: 2015-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2013-12-31

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

OBR + Tenofovir DF

Tenofovir DF administered orally, one tablet daily without regard to meals

Group Type: EXPERIMENTAL

Tenofovir DF

Intervention Type: DRUG

Tenofovir DF 300-mg tablet, administered orally, daily + OBR

OBR + Tenofovir DF Placebo

Placebo to match tenofovir DF administered orally, one tablet daily without regard to meals

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tenofovir DF Placebo administered orally, daily + OBR

Interventions

Tenofovir DF

Tenofovir DF 300-mg tablet, administered orally, daily + OBR

Intervention Type: DRUG

Placebo

Tenofovir DF Placebo administered orally, daily + OBR

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erin Quirk, MD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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

São 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

Countries

Brazil; Panama

Other Identifiers

GS-US-104-0321

Identifier Type: -

Identifier Source: org_study_id