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

Phase 2

Completed

Conditions: HIV-1

Interventions: Drug: F/TAF
Drug: Boosted PIs
Drug: 3rd ARV agent

Registration Number: NCT02285114

Lead Sponsor: Gilead Sciences

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
FTC/TAF+3rd ARV agent (Cohort 3, Part A)	F/TAF	Participants between 2 to \< 6 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
F/TAF+3rd ARV agent (Cohort 2, Group 1, Part A)	Boosted PIs	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.
F/TAF+3rd ARV agent (Cohort 1)	F/TAF	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.
F/TAF+3rd ARV agent (Cohort 2, Group 2, Part A)	F/TAF	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.
F/TAF+3rd ARV agent (Cohort 2, Group 1, Part A)	F/TAF	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.
F/TAF+3rd ARV agent (Cohort 2, Group 2, Part A)	3rd ARV agent	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.
F/TAF+3rd ARV agent (Cohort 2, Group 1, Part B)	3rd ARV agent	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.
FTC/TAF+3rd ARV agent (Cohort 4, Part B)	F/TAF	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.
F/TAF+3rd ARV agent (Cohort 1)	3rd ARV agent	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.
FTC/TAF+3rd ARV agent (Cohort 3, Part A)	3rd ARV agent	Participants between 2 to \< 6 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
FTC/TAF+3rd ARV agent (Cohort 4, Part B)	3rd ARV agent	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.
F/TAF+3rd ARV agent (Cohort 2, Group 2, Part B)	3rd ARV agent	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.
FTC/TAF+3rd ARV agent (Cohort 4, Part A)	3rd ARV agent	Participants between 1 month to \< 2 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
F/TAF+3rd ARV agent (Cohort 2, Group 1, Part B)	F/TAF	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.
F/TAF+3rd ARV agent (Cohort 2, Group 2, Part B)	F/TAF	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.
FTC/TAF+3rd ARV agent (Cohort 3, Part B)	3rd ARV agent	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.
FTC/TAF +3rd ARV agent (Extension Phase)	3rd ARV agent	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.
FTC/TAF+3rd ARV agent (Cohort 4, Part A)	F/TAF	Participants between 1 month to \< 2 years of age will receive F/TAF plus a 3rd ARV agent through 48 weeks.
FTC/TAF +3rd ARV agent (Extension Phase)	F/TAF	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.
FTC/TAF+3rd ARV agent (Cohort 3, Part B)	F/TAF	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)	Any time at Week 2 visit	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24	Baseline 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.
PK Parameter (Cohort 2): AUCtau 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	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in CD4+ Cell Count at Week 48	Baseline, Week 48
PK Parameter (Cohort 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	Cmax is defined as the maximum concentration of drug.
PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV	Any time at Week 2 visit	Cmax is defined as the maximum concentration of drug.
PK Parameter (Cohort 1): Clast of TAF	Any time at Week 2 visit	Clast is defined as the last observable concentration of drug.
PK Parameter (Cohort 1): CL/F of TAF	Any time at Week 2 visit	CL/F is defined as the apparent oral clearance following administration of the drug.
PK Parameter (Cohort 1): Ctau of FTC and TFV	Any time at Week 2 visit	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter (Cohort 1): Vz/F of TAF	Any time at Week 2 visit	Vz/F is defined as the apparent volume of distribution of the drug.
PK Parameter (Cohort 2): Vz/F 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	Vz/F is defined as the apparent volume of distribution of the drug.
PK Parameter (Cohort 1): AUCtau of FTC and TFV	Any time at Week 2 visit	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
PK Parameter (Cohort 2): AUCtau of 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	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
PK Parameter (Cohort 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	Clast is defined as the last observable concentration of drug.
PK Parameter (Cohort 2): CL/F 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	CL/F is defined as the apparent oral clearance following administration of the drug.
PK Parameter (Cohort 2): Ctau of 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	Ctau is defined as the observed drug concentration at the end of the dosing interval.
Percentage of Participants Experiencing TEAEs and SAEs Through Week 48	Baseline 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.
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	Week 24	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.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm	Week 48	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.
Change From Baseline in CD4 Percentage at Week 48	Baseline, Week 48
Percentage of Participants With Palatability of F/TAF Formulation	Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2)	Palatability was reported based on the product taste of being normal or abnormal. Missing data were reported separately.
Percentage of Participants With Acceptability of F/TAF Formulation	Baseline up to Week 4	Acceptability was reported based on the the product size and shape. Missing data were reported separately.
Change From Baseline in CD4+ Cell Count at Week 24	Baseline, Week 24
Change From Baseline in CD4 Percentage at Week 24	Baseline, Week 24

Trial Locations

Locations (8): University of California Los Angeles
🇺🇸
Los Angeles, California, United States
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
St. Christopher's Hospital for Children
🇺🇸
Philadelphia, Pennsylvania, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Rahima Moosa Mother and Child Hospital
🇿🇦
Johannesburg, Coronationville, South Africa
KIDCRU, Ward J8, Tygerberg Children's Hospital
🇿🇦
Cape Town, South Africa
Be Part Yoluntu Centre
🇿🇦
Cape Town, South Africa
Hospital del Nino
🇵🇦
Panama City, Panama