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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00352053
First received: July 13, 2006
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

The purpose of this study was to assess the safety and efficacy of tenofovir disoproxil fumarate (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.


Condition Intervention Phase
HIV Infections
Drug: Tenofovir DF
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA [ Time Frame: Baseline to 24 Weeks ] [ Designated as safety issue: No ]
    DAVG24 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 24 minus the baseline value. DAVG24 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value.


Secondary Outcome Measures:
  • Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    DAVG48 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 48 minus the baseline value. DAVG48 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value.

  • Change From Baseline to Week 24 in HIV-1 RNA [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    Change = Week 24 value minus baseline value

  • Change From Baseline to Week 48 in HIV-1 RNA [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    Change = Week 48 value minus baseline value

  • Change From Baseline to Week 96 in HIV-1 RNA [ Time Frame: Baseline to 96 weeks ] [ Designated as safety issue: No ]
    Change = Week 96 value minus baseline value

  • Change From Baseline to Week 144 in HIV-1 RNA [ Time Frame: Baseline to 144 weeks ] [ Designated as safety issue: No ]
    Change = Week 144 value minus baseline value

  • Change From Baseline to Week 192 in HIV-1 RNA [ Time Frame: Baseline to 192 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 240 in HIV-1 RNA [ Time Frame: Baseline to 240 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 288 in HIV-1 RNA [ Time Frame: Baseline to 288 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 336 in HIV-1 RNA [ Time Frame: Baseline to 336 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    Change = Week 24 value minus baseline value

  • Change From Baseline to Week 48 in CD4 Count [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    Change = Week 48 value minus baseline value

  • Change From Baseline to Week 96 in CD4 Count [ Time Frame: Baseline to 96 weeks ] [ Designated as safety issue: No ]
    Change = Week 96 value minus baseline value

  • Change From Baseline to Week 144 in CD4 Count [ Time Frame: Baseline to 144 weeks ] [ Designated as safety issue: No ]
    Change = Week 144 value minus baseline value

  • Change From Baseline to Week 192 in CD4 Count [ Time Frame: Baseline to 192 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 240 in CD4 Count [ Time Frame: Baseline to 240 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 288 in CD4 Count [ Time Frame: Baseline to 288 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 336 in CD4 Count [ Time Frame: Baseline to 336 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 24 in CD4 Percentage [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    Change = Week 24 value minus baseline value. CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

  • Change From Baseline to Week 48 in CD4 Percentage [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    Change = Week 48 value minus baseline value. CD4 percentage is the percentage of total lymphocytes that are CD4 cells.

  • Change From Baseline to Week 96 in CD4 Percentage [ Time Frame: Baseline to 96 weeks ] [ Designated as safety issue: No ]
    Change = Week 96 value minus baseline value

  • Change From Baseline to Week 144 in CD4 Percentage [ Time Frame: Baseline to 144 weeks ] [ Designated as safety issue: No ]
    Change = Week 144 value minus baseline value

  • Change From Baseline to Week 192 in CD4 Percentage [ Time Frame: Baseline to 192 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 240 in CD4 Percentage [ Time Frame: Baseline to 240 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline to Week 288 in CD4 Percentage [ Time Frame: Baseline to 288 weeks ] [ Designated as safety issue: No ]
  • Change From Baseline in Week 336 in CD4 Percentage [ Time Frame: Baseline to 336 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 24 [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    The percentage of participants achieving a plasma HIV-1 RNA decrease of >= 1.0 log10 copies/mL from baseline at Week 24 was summarized.

  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 48 [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    The percentage of participants achieving a plasma HIV-1 RNA decrease of >= 1.0 log10 copies/mL from baseline at Week 48 was summarized.

  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 96 [ Time Frame: Baseline to 96 weeks ] [ Designated as safety issue: No ]
    The percentage of participants achieving a plasma HIV-1 RNA decrease of >= 1.0 log10 copies/mL from baseline at Week 96 was summarized.

  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 144 [ Time Frame: Baseline to 144 weeks ] [ Designated as safety issue: No ]
    The percentage of participants achieving a plasma HIV-1 RNA decrease of >= 1.0 log10 copies/mL from baseline at Week 144 was summarized.

  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 192 [ Time Frame: Baseline to 192 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0 log10 Copies/mL From Baseline to Week 240 [ Time Frame: Baseline to 240 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0log10 Copies/mL From Baseline to Week 288 [ Time Frame: Baseline to 288 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With an HIV-1 RNA Decrease of >= 1.0log10 Copies/mL From Baseline to Week 336 [ Time Frame: Baseline to 336 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 400 copies/mL at Week 24 was summarized.

  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 400 copies/mL at Week 48 was summarized.

  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 400 copies/mL at Week 96 was summarized.

  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 400 copies/mL at Week 144 was summarized.

  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192 [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240 [ Time Frame: Week 240 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288 [ Time Frame: Week 288 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336 [ Time Frame: Week 336 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized.

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized.

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 96 was summarized.

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 [ Time Frame: Week 144 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 144 was summarized.

  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240 [ Time Frame: Week 240 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288 [ Time Frame: Week 288 ] [ Designated as safety issue: No ]
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336 [ Time Frame: Week 336 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Virologic Failure at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Virologic failure was defined as participants who never responded (response was defined as either a >= 0.5 log10 decrease from baseline in HIV-1 RNA in 2 consecutive visits or HIV-1 RNA < 400 copies/mL in 2 consecutive visits) or who had a rebound after achieving a response (rebound was defined as >= 1 log10 increase from nadir, or >= the baseline value, or > 1000 copies/mL in 2 consecutive visits). The virologic failure rate at Week 48 was estimated from Kaplan-Meier product limit method by including all HIV-1 RNA data collected during the double-blind phase.


Enrollment: 87
Study Start Date: July 2006
Study Completion Date: December 2013
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OBR + Tenofovir DF
Tenofovir DF administered orally, one tablet daily without regard to meals.
Drug: Tenofovir DF
Tenofovir DF 300-mg tablet, administered orally, daily + OBR
Placebo Comparator: OBR + Tenofovir DF Placebo Drug: Placebo
Tenofovir DF Placebo administered orally, daily + OBR

Detailed Description:

This was 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 were failing their current antiretroviral regimen and had HIV-1 RNA levels >= 1000 copies/mL at screening. Data from three consecutive 96-week study extensions (ongoing) 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 was 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 were randomized in a 1:1 ratio to receive either tenofovir DF + OBR or placebo + OBR. The majority of efficacy and safety assessments were performed at each clinic visit (Weeks 4, 8, 16, 24, 32, 40, and 48). At Week 24, participants who were adherent to study drug (in the opinion of the investigator), but did not demonstrate a >= 0.5 log10 copies/mL decrease from baseline in HIV-1 RNA, were considered to be nonresponders and were unblinded. Nonresponders randomized to the placebo group were 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 were discontinued from the study.

Extension Phases:

After completing 48 weeks of double-blind treatment with tenofovir DF or placebo, participants who had 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, were 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 received open-label tenofovir DF after Week 24 were also 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 had not reached 18 years of age, and who had shown ongoing clinical benefit from tenofovir DF, were 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 were enrolled, whichever occurred first.

After completing the second 96 week study extension, participants who had not reached 18 years of age, and who had shown ongoing clinical benefit from tenofovir DF, were 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 were enrolled, whichever occurred first.

Presentation of data:

Participants who were randomized to placebo during the randomized phase of the study and then switched to open-label tenofovir DF had their baseline reset (defined as open-label baseline), and only outcome data collected after (on/after for AEs/concomitant medications) participants received their first dose of open-label tenofovir DF were included in this entry.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Major Inclusion Criteria:

  • Weight greater than or equal to 35 kg
  • Documented laboratory diagnosis of HIV infection
  • Plasma HIV-1 RNA greater than or equal to 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352053

Locations
Brazil
Santa Casa de Belo Horizonte
Belo Horizonte - MG, Brazil
Faculdade de Medicina - UFMG
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
NEIMPE - Dept of Pediatrics Hospital das Clinicas FMRP-USP
Sao Paulo, Brazil
Instituto de Infectologia Emilio Ribas
Sao Paulo - SP, Brazil
Instituto da Crianca do Hospital das Clinicas da FMUSP Depto de Pediatria
Sao Paulo - SP, Brazil
Universidade Federal de Sao Paulo
Vila Clementino, Brazil
Hospital Infantil Nossa Senhora da Gloria Servico de Infectologia Pediatria
Vitoria - ES, Brazil
Panama
Hospital del Nino
Panama City, Panama
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Erin Quirk, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00352053     History of Changes
Other Study ID Numbers: GS-US-104-0321
Study First Received: July 13, 2006
Results First Received: March 5, 2010
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Panama: Commemorative Institute GORGAS of Studies of Health

Keywords provided by Gilead Sciences:
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 21, 2014