Clinical trial NCT02285114: Study To Evaluate Emtricitabine/Tenofovir Alafenamide (F/TAF) in Human Immunodeficiency Virus 1 (HIV-1) Infected Children and Adolescents Virologically Suppressed on a 2- Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (2-NRTI)-Containing Regimen
Official title: A Phase 2/3, Open-Label, Multi-Cohort Switch Study to Evaluate Emtricitabine/Tenofovir Alafenamide (F/TAF) in HIV-1 Infected Children and Adolescents Virologically Suppressed on a 2-NRTI-Containing Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV-1
Keywords: emtricitabine
FTC
tenofovir
TDF
antiretroviral
adolescents
children
pediatric
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-11-06
Enrollment: 41
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to confirm the TAF dose and to evaluate the pharmacokinetics (PK) of TAF, safety, and tolerability of F/TAF in HIV-1 infected children and adolescents virologically suppressed (defined as having \< 50 copies/mL of HIV-1 ribonucleic acid \[RNA\] for a period of at least 6 months) while on a stable NRTI containing regimen.

Detailed description: Cohorts 2, 3, and 4 will be on a boosted protease inhibitor (PI) or any other 3rd antiretroviral (ARV) agent and will switch their current 2-NRTI-containing regimen to open-label F/TAF while continuing their boosted PI or 3rd agent through 48 weeks. A minimum of 10 participants each in Groups 1 and 2 of Cohort 2, and Cohorts 3 and 4, who are on boosted-atazanavir (ATV) as their 3rd ARV agent will be enrolled. Participants in Cohort 2, Group 1 receive boosted PI agents only. Cohorts 2, 3, and 4 will be enrolled by cohort into a two-part study (Parts A and B).

After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) The participant turns 18 years old and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or b), F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or c), Gilead Sciences elects to terminate development of F/TAF in the applicable country.

Eligibility criteria: Key Inclusion Criteria:

* HIV-1 infected male and female adolescents and children aged 1 month to \< 18 years at baseline/Day 1 (according to requirements of the enrolling cohort)
* Must be able to give written assent prior to any screening evaluations
* Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
* Body weight at screening as follows:

  * Cohort 1: ≥ 35 kg
  * Cohort 2, Group 1: ≥ 25 kg
  * Cohort 2, Group 2: 17 kg to \< 25 kg
  * Cohort 3: to be updated per a protocol amendment
  * Cohort 4: to be updated per a protocol amendment
* Currently on a stable 2-NRTI containing regimen that includes a 3rd ARV agent for ≥ 6 consecutive months prior to screening
* Plasma HIV-1 RNA levels \< 50 copies/mL for ≥ 6 consecutive months preceding the screening visit
* No opportunistic infection within 30 days of study entry (at baseline/Day 1)
* A negative serum β-human chorionic gonadotropin (HCG) pregnancy test is required for females of childbearing potential only

Key Exclusion Criteria:

* An acquired immunodeficiency syndrome (AIDS) - indicator condition with onset within 30 days prior to screening
* Life expectancy of \< 2 years
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline/Day 1
* Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
* Active hepatitis C virus (HCV) infection defined as positive for HCV antibody and having detectable HCV RNA
* Positive hepatitis B surface antigen or other evidence of active hepatitis B virus (HBV) infection.
* Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment, or compliance with the protocol.
* Pregnant or lactating females
* Have history of significant drug sensitivity or drug allergy
* Have previously participated in an investigational trial involving administration of any investigational agent, other than tenofovir, within 30 days prior to the study dosing

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2): AUCtau of TAF
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24
timeFrame: Baseline through Week 24
Secondary outcomes:
measure: PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2): Cmax of TAF, FTC, and TFV
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: PK Parameter (Cohort 1): Clast of TAF
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2) : Clast of TAF
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: PK Parameter (Cohort 1): CL/F of TAF
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2): CL/F of TAF
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: PK Parameter (Cohort 1): Vz/F of TAF
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2): Vz/F of TAF
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: PK Parameter (Cohort 1): AUCtau of FTC and TFV
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2): AUCtau of FTC and TFV
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: PK Parameter (Cohort 1): Ctau of FTC and TFV
timeFrame: Any time at Week 2 visit
measure: PK Parameter (Cohort 2): Ctau of FTC and TFV
timeFrame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
measure: Percentage of Participants Experiencing TEAEs and SAEs Through Week 48
timeFrame: Baseline through Week 48
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in CD4 Percentage at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in CD4 Percentage at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants With Palatability of F/TAF Formulation
timeFrame: Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2)
measure: Percentage of Participants With Acceptability of F/TAF Formulation
timeFrame: Baseline up to Week 4
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Panama City
country: Panama
facility: Hospital del Nino
city: Johannesburg
country: South Africa
facility: Rahima Moosa Mother and Child Hospital
state: Coronationville
city: Cape Town
country: South Africa
facility: KIDCRU, Ward J8, Tygerberg Children's Hospital
city: Cape Town
country: South Africa
facility: Be Part Yoluntu Centre
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: