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 RNAChange 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
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