HIV-1Phase 2/3NCT02285114
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
A Phase 2/3 study testing F/TAF, 3rd ARV agent and Boosted PIs in people with HIV-1, run by Gilead Sciences at 8 sites in 3 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 1 month to 17 years
- Conditions the study is for
- HIV-1
- What is being tested?
- F/TAF, 3rd ARV agent and Boosted PIs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 20 Jan 2015to 11 Dec 2024
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
- NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States4 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
University of California Los Angeles
Los Angeles, California, 90095
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Seattle Children's Hospital
Seattle, Washington, 98105-0371
South Africa3 sites
KIDCRU, Ward J8, Tygerberg Children's Hospital
Cape Town, 7505
Be Part Yoluntu Centre
Cape Town, 7626
Rahima Moosa Mother and Child Hospital
Johannesburg, Coronationville, 2093
About this study
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
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.
Read the detailed description
A minimum of 100 participants in total (across all cohorts) aged 1 month to <18 years of age will be enrolled to receive F/TAF. The study will proceed in sequential cohorts as follows: Cohort 1 will switch their current 2-NRTI-containing regimen to F/TAF while continuing on their 3rd ARV agent through 48 weeks; Cohorts 2, 3, and 4 must be on a boosted protease inhibitor (PI) (Cohort 2 only) or any other 3rd ARV agent and will switch their current 2-NRTI-containing regimen to F/TAF while continuing their boosted PI or 3rd ARV 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-ATV as their 3rd ARV agent will be enrolled. 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.
However, Cohort 2 (Part B), Cohorts 3 and 4 were not conducted as planned.
- Conditions
- HIV-1
- Being tested
- F/TAF, 3rd ARV agent, Boosted PIs
- Keywords
- emtricitabine, FTC, tenofovir, TDF, antiretroviral, adolescents, children, pediatric, TAF
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
F/TAFDrug
F/TAF tablets administered orally once daily
3rd ARV agentDrug
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)
Boosted PIsDrug
Allowed boosted PIs: LPV, ATV, DRV.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: F/TAF; Drug: 3rd ARV agent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline through Week 24
Secondary outcomes (21)
PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV
Cmax is defined as the maximum concentration of drug.
Measured: Any time at Week 2 visit
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV
Cmax is defined as the maximum concentration of drug.
Measured: 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
Clast is defined as the last observable concentration of drug.
Measured: Any time at Week 2 visit
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF
Clast is defined as the last observable concentration of drug.
Measured: 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
CL/F is defined as the apparent clearance following oral administration of the drug.
Measured: Any time at Week 2 visit
PK Parameter (Cohort 2: Part A - Groups 1 and 2): CL/F of TAF
CL/F is defined as the apparent clearance following oral administration of the drug.
Measured: 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): Vz/F of TAF
Vz/F is defined as the apparent volume of distribution of the drug following oral administration.
Measured: Any time at Week 2 visit
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Vz/F of TAF
Vz/F is defined as the apparent volume of distribution of the drug following oral administration.
Measured: 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): AUCtau of FTC and TFV
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Measured: Any time at Week 2 visit
PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Measured: 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): Ctau of FTC and TFV
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Measured: Any time at Week 2 visit
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Measured: 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 TEAEs and SAEs Through Week 48
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.
Measured: Baseline through Week 48
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
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measured: Week 24
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Measured: Week 48
Change From Baseline in CD4+ Cell Count at Week 24
Measured: Baseline, Week 24
Change From Baseline in CD4+ Cell Count at Week 48
Measured: Baseline, Week 48
Change From Baseline in CD4 Percentage at Week 24
Measured: Baseline, Week 24
Change From Baseline in CD4 Percentage at Week 48
Measured: Baseline, Week 48
Number of Participants With Palatability of F/TAF Formulation
Palatability was reported based on the pleasant product taste as 'Yes' or 'No'. Data has been reported for Participant Response (PR) and Guardian Response (GR). Participants with missing data were reported as N/A.
Measured: Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2)
Number of Participants With Acceptability of F/TAF Formulation
Acceptability has been reported for categories medication size, shape and difficulty swallowing as 'Yes' or 'No' for Participant Response (PR) and Guardian Response (GR). Participants with missing data were reported as N/A.
Measured: Baseline up to Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2014 (estimated)
- Study start20 Jan 2015
- Primary completion4 Nov 2019
- Study completion11 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for HIV-1Studies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02285114
- Sponsor's protocol ID
- GS-US-311-1269
- Other IDs
- 2015-001339-19, 2015
- Status last verified
- Jun 2025
- First submitted
- 4 Nov 2014
- Last updated
- 27 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment
Publications
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.
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.
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.
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.
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.
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.
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.
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.
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.