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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 87
- Locations
- 18
- Primary Endpoint
- Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 12 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
OBR + Tenofovir DF
Tenofovir DF administered orally, one tablet daily without regard to meals
Intervention: Tenofovir DF (Drug)
OBR + Tenofovir DF Placebo
Placebo to match tenofovir DF administered orally, one tablet daily without regard to meals
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA
Time Frame: Baseline to 24 Weeks
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. Data for participants who discontinued the randomized (double-blind) phase of the study early were included up until the point of study discontinuation (missing data not imputed).
Secondary Outcomes
- Change From Baseline to Week 288 in HIV-1 RNA(Baseline to 288 weeks)
- Change From Baseline to Week 48 in CD4 Count(Baseline to 48 weeks)
- Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA(Baseline to 48 weeks)
- Change From Baseline to Week 24 in HIV-1 RNA(Baseline to 24 weeks)
- Change From Baseline to Week 48 in HIV-1 RNA(Baseline to 48 weeks)
- Change From Baseline to Week 96 in HIV-1 RNA(Baseline to 96 weeks)
- Change From Baseline to Week 144 in HIV-1 RNA(Baseline to 144 weeks)
- Change From Baseline to Week 192 in HIV-1 RNA(Baseline to 192 weeks)
- Change From Baseline to Week 240 in HIV-1 RNA(Baseline to 240 weeks)
- Change From Baseline to Week 336 in HIV-1 RNA(Baseline to 336 weeks)
- Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count(Baseline to 24 weeks)
- Change From Baseline to Week 96 in CD4 Count(Baseline to 96 weeks)
- Change From Baseline to Week 24 in CD4 Percentage(Baseline to 24 weeks)
- Change From Baseline to Week 240 in CD4 Percentage(Baseline to 240 weeks)
- Change From Baseline to Week 336 in CD4 Percentage(Baseline to 336 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336(Baseline to 336 weeks)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288(Week 288)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24(Week 24)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144(Week 144)
- Change From Baseline to Week 144 in CD4 Count(Baseline to 144 weeks)
- Change From Baseline to Week 288 in CD4 Count(Baseline to 288 weeks)
- Change From Baseline to Week 336 in CD4 Count(Baseline to 336 weeks)
- Change From Baseline to Week 96 in CD4 Percentage(Baseline to 96 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144(Baseline to 144 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192(Baseline to 192 weeks)
- Change From Baseline to Week 192 in CD4 Count(Baseline to 192 weeks)
- Change From Baseline to Week 240 in CD4 Count(Baseline to 240 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240(Baseline to 240 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288(Baseline to 288 weeks)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48(Week 48)
- Change From Baseline to Week 48 in CD4 Percentage(Baseline to 48 weeks)
- Change From Baseline to Week 144 in CD4 Percentage(Baseline to 144 weeks)
- Change From Baseline to Week 192 in CD4 Percentage(Baseline to 192 weeks)
- Change From Baseline to Week 288 in CD4 Percentage(Baseline to 288 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24(Baseline to 24 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96(Baseline to 96 weeks)
- Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48(Baseline to 48 weeks)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24(Week 24)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336(Week 336)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144(Week 144)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192(Week 192)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240(Week 240)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240(Week 240)
- Percentage of Participants With Virologic Failure Through Week 48(Up to 48 weeks)
- Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336(Week 336)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192(Week 192)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288(Week 288)