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

NCT02285114 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: GS-US-311-12692015-001339-19
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 8

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 children and adolescents with HIV-1 who are 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 2 NRTI containing regimen.

Conditions

HIV-1

Keywords

emtricitabine; FTC; tenofovir; TDF; antiretroviral; adolescents; children; pediatric; TAF

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)

  AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.

  Any time at Week 2 visit

• PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of TAF

  AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.

  Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24

  An AE is any untoward medical occurrence in a clinical study participant which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The TEAEs were defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.

  Baseline through Week 24

Secondary Outcomes (21)

• PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV

  Any time at Week 2 visit

• PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV

  Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits

• PK Parameter (Cohort 1): Clast of TAF

  Any time at Week 2 visit

• PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF

  Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits

• PK Parameter (Cohort 1): CL/F of TAF

  Any time at Week 2 visit

Study Arms (10)

F/TAF+3rd ARV Agent (Cohort 1)

EXPERIMENTAL

Participants between 12 to \< 18 years of age and ≥ 35 kg in body weight will switch their current 2-NRTI containing regimen to F/TAF (200/25 mg for unboosted 3rd agent and 200/10 mg for boosted 3rd agent) while continuing on their 3rd ARV agent for 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1)

EXPERIMENTAL

Participants between 6 to \< 12 years of age and ≥ 25 kg in body weight must be on a boosted protease inhibitor (PI) as their 3rd ARV agent and will switch their current 2-NRTI regimen to F/TAF 200/25 mg while continuing on their boosted PI for 48 weeks.

Drug: F/TAF; Drug: Boosted PIs

F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2)

EXPERIMENTAL

Participants between 2 to \< 12 years of age and between 17 kg to \< 25 kg in body weight must be on a boosted protocol specified 3rd ARV agent and will switch their current 2-NRTI containing regimen to F/TAF 120/15 mg while continuing their 3rd ARV agent for 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

FTC/TAF+3rd ARV Agent (Cohort 3, Part A)

EXPERIMENTAL

Participants between 2 to \< 6 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

FTC/TAF+3rd ARV Agent (Cohort 4, Part A)

EXPERIMENTAL

Participants between 1 month to \< 2 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 1)

EXPERIMENTAL

Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 2)

EXPERIMENTAL

Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

FTC/TAF+3rd ARV Agent (Cohort 3, Part B)

EXPERIMENTAL

Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

FTC/TAF+3rd ARV Agent (Cohort 4, Part B)

EXPERIMENTAL

Screening will be initiated for Part B following confirmation of TAF dose in Part A. Approximately 10 additional total participants will be enrolled across all Part B cohorts and will receive F/TAF while continuing their 3rd ARV agent through 48 weeks.

Drug: F/TAF; Drug: 3rd ARV agent

FTC/TAF+3rd ARV Agent (Extension Phase)

EXPERIMENTAL

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 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.

Drug: F/TAF; Drug: 3rd ARV agent

Interventions

F/TAF DRUG

F/TAF tablets administered orally once daily

F/TAF+3rd ARV Agent (Cohort 1); F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1); F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2); F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 1); F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 2); FTC/TAF+3rd ARV Agent (Cohort 3, Part A); FTC/TAF+3rd ARV Agent (Cohort 3, Part B); FTC/TAF+3rd ARV Agent (Cohort 4, Part A); FTC/TAF+3rd ARV Agent (Cohort 4, Part B); FTC/TAF+3rd ARV Agent (Extension Phase)

3rd ARV agent DRUG

A 3rd antiretroviral (ARV) agent may include one of the following: allowed boosted 3rd ARV agents: lopinavir (LPV), atazanavir (ATV), darunavir (DRV); Allowed unboosted 3rd ARV agents: efavirenz (EFV), raltegravir (RAL), dolutegravir (DTG), or nevirapine (NVP)

F/TAF+3rd ARV Agent (Cohort 1); F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2); F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 1); F/TAF+3rd ARV Agent (Cohort 2, Part B - Group 2); FTC/TAF+3rd ARV Agent (Cohort 3, Part A); FTC/TAF+3rd ARV Agent (Cohort 3, Part B); FTC/TAF+3rd ARV Agent (Cohort 4, Part A); FTC/TAF+3rd ARV Agent (Cohort 4, Part B); FTC/TAF+3rd ARV Agent (Extension Phase)

Boosted PIs DRUG

Allowed boosted PIs: LPV, ATV, DRV.

F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1)

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Human immunodeficiency virus 1 (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-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) containing regimen that includes a 3rd antiretroviral (ARV) agent for ≥ 6 consecutive months prior to screening
• Plasma HIV-1 ribonucleic acid (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

You may not qualify if:

• 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 TDF, within 30 days prior to the study dosing

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (8)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105-0371, United States

Location

Hospital del Nino

Panama City, 0816-00383, Panama

Location

Rahima Moosa Mother and Child Hospital

Johannesburg, Coronationville, 2093, South Africa

Location

KIDCRU, Ward J8, Tygerberg Children's Hospital

Cape Town, 7505, South Africa

Location

Be Part Yoluntu Centre

Cape Town, 7626, South Africa

Location

Related Publications (9)

• Chen JS, Saez-Llorens X, Castano E, Patel F, Melvin A, McFarland EJ, et al. Safety, Pharmacokinetics, and Efficacy of FTC/TAF in HIV-Infected Adolescents (12-18 years) [Poster 843]. Conference on Retroviruses and Opportunistic Infections (CROI); 2018 04-07 March; Boston, MA.

  BACKGROUND

• Castano E, Deville J, Zuidewind P, Vedder J, German P, Mathias A, et al. PK and Safety of F/TAF With Boosted 3rd Agents in Children With HIV [Abstract 54]. International Workshop on HIV & Pediatrics 2020; 2020 November 16-17 Virtual.

  BACKGROUND

• Cox S, Porter D, White K, Graham H, Pikora C, Callebaut C. Tenofovir Alafenamide-Based Regimens: A Pooled Resistance Analysis in Pediatric Participants [Abstract 4]. International Workshop on HIV Pediatrics 2019; 2019 July 19-20; San Francisco, CA.

  BACKGROUND

• Rakhmanina N, Cunningham C, Cotton M, Natukunda E, Rodriguez C, Gaur A, et al. Weight Trajectory in Children and Adolescents Who Switched to TAF-Based Regimens [Abstract 56]. International Workshop on HIV & Pediatrics 2020; 2020 November 16-17; Virtual.

  BACKGROUND

• Sharma S, Gupta S, Majeed SR, Strehlau R, Hellstrom E, Liu Y, et al. Exposure-Safety of Tenofovir in Pediatric HIV Infected Participants: Comparison of Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate [Abstract 23]. Presented at International Workshop on HIV Pediatrics 2018; 2018 July 20-21; Amsterdam, The Netherlands.

  BACKGROUND

• Cotton M, Cunningham C, Natukunda E, Rodriguez C, Gaur A, Kosalaraksa P, et al. Lack of Influence of Pubertal Stage on Safety and TFV Pharmacokinetics in TAF-based Regimens [Abstract 43]. International Workshop on HIV Pediatrics 2019; 2019 July 19-20; San Francisco, CA.

  BACKGROUND

• Andreatta K, Cox S, Chokephaibulkit K, Rodriguez C, Liberty A, Natukunda E, et al. Preexisting and Post-Baseline Resistance Analyses in Pooled Pediatric Studies of Emtricitabine/Tenofovir Alafenamide (F/TAF)-Based Antiretroviral Therapy. 12th IAS Conference on HIV Science; 2023 23-26 July; Brisbane, Australia.

  BACKGROUND

• Rakhmanina N, Gaur A, Deville JG, Kosalaraksa P, Strehlau R, Natukunda E, et al. Bone Mineral Density in Children With HIV 1 Receiving TAF Based Antiretroviral Therapy [Abstract 948]. Conference on Retroviruses and Opportunistic Infections (CROI); 2024 03-06 March; Denver, CO.

  BACKGROUND

• Mujuru H, Strehlau R, Kosalaraksa A, Deville JG, Pan M, Vieira VA, et al. Week 24 Outcomes of F/TAF Plus Cobicistat-Boosted Protease Inhibitors in Children ≥ 2 Years and ≥ 14 kg [Abstract] Presented at Conference on Retroviruses an Opportunistic Infections (CROI); 2025 09-12 March, San Francisco, CA.

  BACKGROUND

Related Links

• Gilead Clinical Trials Website

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 6, 2014
• Study Start: January 20, 2015
• Primary Completion: November 4, 2019
• Study Completion: December 11, 2024
• Last Updated: June 27, 2025
• Results First Posted: January 12, 2021

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

ZA (3); US (4); PA (1)