Safety and Efficacy of Tenofovir DF in HIV-1 Infected Adolescents Failing Their Current Antiretroviral Therapy
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Tenofovir DF; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Tenofovir DF 300-mg tablet, administered orally, daily + OBR; Tenofovir DF Placebo administered orally, daily + OBR
Intervention MeSH terms: Tenofovir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
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