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

Gilead Sciences41 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 1 MonthMax age: 17 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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 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 TDF, within 30 days prior to the study dosing NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline through Week 24

Secondary Outcomes

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

Cmax is defined as the maximum concentration of drug.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: Week 48

Change From Baseline in CD4+ Cell Count at Week 24

Time frame: Baseline, Week 24

Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline, Week 48

Change From Baseline in CD4 Percentage at Week 24

Time frame: Baseline, Week 24

Change From Baseline in CD4 Percentage at Week 48

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to Week 4

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

Overview

Conditions

Interventions

Eligibility

Locations (8)

Outcomes

Primary Outcomes

Secondary Outcomes