Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children

Gilead Sciences129 enrolled

Overview

The primary objectives of Cohort 1 are to evaluate the steady state pharmacokinetics (PK) for elvitegravir (EVG) and tenofovir alafenamide (TAF) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) STR (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 (Part B) in human immunodeficiency virus - 1 (HIV-1) infected, antiretroviral (ARV) treatment-naive adolescents. The primary objectives of Cohort 2 are to evaluate the PK of EVG and TAF (Part A), and to evaluate the safety and tolerability of E/C/F/TAF through Week 24 (Part B) in virologically suppressed HIV-1 infection children 6 to \< 12 years weighing \>= 25 kg. The primary objectives of Cohort 3 are to evaluate the PK of EVG and TAF and confirm the dose of the STR, and to evaluate the safety and tolerability of E/C/F/TAF low dose (LD) STR in virologically suppressed HIV-1 infected children ≥ 2 years of age and weighing ≥ 14 to \< 25 kg.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

129

Conditions

Acquired Immune Deficiency Syndrome (AIDS)HIV Infections

E/C/F/TAFDRUG

Tablets administered orally with food.

E/C/F/TAF (Low Dose)DRUG

90/90/120/6 mg STR administered once daily orally with food.

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Cohort 1 * Age at baseline: 12 years to \< 18 years old * Weight at screening: ≥ 35 kg (77 lbs) * Plasma HIV-1 ribonucleic acid (RNA) levels of ≥ 1,000 copies/mL at screening (Roche COBAS TaqMan v2.0) * Screening genotype report shows sensitivity to EVG, emtricitabine (FTC) and tenofovir (TFV) * No prior use of any approved or experimental anti-HIV-1 drug for any length of time * Cohort 2 * Age at baseline: 6 years to \< 12 years old * Weight at screening: ≥ 25 kg (55 lbs) * Plasma HIV-1 RNA of \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without documented history of resistance to any component of E/C/F/TAF STR. * Cohort 3 * Age at baseline: ≥ 2 years old * Weight at screening: ≥ 14 kg (31 lbs) to \< 25 kg (55 lbs) * Plasma HIV-1 RNA: \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 180 consecutive days (6 months) prior to screening on a stable antiretroviral regimen, without prior history of resistance to any component of E/C/F/TAF STR Key Exclusion Criteria: * Hepatitis B or hepatitis C virus infection * Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit. * Individuals experiencing decompensated cirrhosis * Pregnant or lactating females Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (16)

Miller's Children Hospital

Long Beach, California, United States

Children's Research Institute

Washington D.C., District of Columbia, United States

Emory University School of Medicine

Atlanta, Georgia, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Seattle Children's Hospital

Seattle, Washington, United States

KIDCRU Ward J8

Cape Town, South Africa

Be Part Yoluntu Centre

Cape Town, South Africa

Desmond Tutu HIV Foundation

Cape Town, South Africa

Perinatal HIV Research Unit Baragwanath Hospital

Johannesburg, South Africa

Clinical HIV Research Unit

Johannesburg, South Africa

...and 6 more locations

Outcomes

Primary Outcomes

Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG) (Cohort 1)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: AUCtau of EVG (Cohort 2)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: AUCtau of EVG (Cohort 3)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

PK Parameter: AUClast of Tenofovir Alafenamide (TAF) (Cohort 1)

AUClast is defined as the concentration of drug from time zero to the last observable concentration, area under the concentration time curve to last observation (AUClast).

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: AUClast of TAF (Cohort 2)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: AUCtau of TAF (Cohort 3)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

Cohort 1: Percentage of Participants With All Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.

Time frame: From first dose date up to Week 24

Cohort 2: Percentage of Participants With All Treatment-Emergent AEs and Treatment-Emergent SAEs

TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the Gilead Sciences Grading Scale for Severity of Adverse Events. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above.

Time frame: From first dose date up to Week 24

Cohort 3: Percentage of Participants With All Treatment-Emergent AEs and Treatment-Emergent SAEs

Time frame: From first dose date up to Week 24

Secondary Outcomes

PK Parameter: Ctau of EVG, Emtricitabine (FTC), Tenofovir (TFV), and Cobicistat (COBI) (Cohort 1)

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: Ctau of EVG, FTC, TFV and COBI (Cohort 2)

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: Ctau of EVG, FTC, TFV, and COBI (Cohort 3)

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

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

Cmax is defined as the maximum concentration of drug.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 2)

Cmax is defined as the maximum concentration of drug.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 3)

Cmax is defined as the maximum concentration of drug.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

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

Apparent oral clearance (CL/F) is defined as the apparent clearance of the drug following oral administration.

Data from ClinicalTrials.gov

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Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: CL/F of EVG and TAF (Cohort 2)

CL/F is defined as the apparent clearance of the drug following oral administration.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: CL/F of EVG and TAF (Cohort 3)

CL/F is defined as the apparent clearance of the drug following oral administration.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

PK Parameter: Vz/F of EVG and TAF (Cohort 1)

Vz/F is defined as the apparent volume of distribution of the drug after oral administration.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: Vz/F of EVG and TAF (Cohort 2)

Vz/F is defined as the apparent volume of distribution of the drug after oral administration.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: Vz/F of EVG and TAF (Cohort 3)

Vz/F is defined as the apparent volume of distribution of the drug after oral administration.

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 1)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 5 minutes, 0.25, 0.5, 1, 1.5, 2, 4, 5, 8 and 24 hours post-dose at Week 4

PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 2)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours post-dose at Week 4

PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 3)

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

Time frame: 0 (pre-dose, ≤ 30 minutes prior to dosing), 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 8 hours post-dose at Week 2

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines 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

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines 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

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis

The percentage of participants with HIV-1 RNA \< 400 Copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines 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

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis

The percentage of participants with HIV-1 RNA \< 400 Copies/mL at Weeks 24 and 48 was analyzed using the snapshot algorithm, which defines 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

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis

Time frame: Week 24

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis

Time frame: Week 48

Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis

Time frame: Week 24

Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis

Time frame: Week 48

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.

Time frame: Week 24

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed based on missing = failure analyses.

Time frame: Week 48

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.

Time frame: Week 24

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed based on missing = failure analyses.

Time frame: Week 48

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.

Time frame: Week 24

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed based on missing = failure analyses.

Time frame: Week 48

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed based on missing = failure analyses.

Time frame: Week 24

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed based on missing = failure analyses.

Time frame: Week 48

Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.

Time frame: Week 24

Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed based on missing = failure analyses.

Time frame: Week 48

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = excluded analyses.

Time frame: Week 24

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed based on missing = excluded analyses.

Time frame: Week 48

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed based on missing = excluded analyses.

Time frame: Week 24

Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed based on missing = excluded analyses.

Time frame: Week 48

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = excluded analyses.

Time frame: Week 24

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed based on missing = excluded analyses.

Time frame: Week 48

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed based on missing = excluded analyses.

Time frame: Week 24

Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed based on missing = excluded analyses.

Time frame: Week 48

Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed based on missing = excluded analyses.

Time frame: Week 24

Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses

The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed based on missing = excluded analyses.

Time frame: Week 48

Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24

Time frame: Baseline, Week 24

Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Week 48

Time frame: Baseline, Week 48

Cohort 1: Change From Baseline in Cluster of Differentiation (CD4+) Cell Count at Week 24

Time frame: Baseline, Week 24

Cohort 1: Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline, Week 48

Cohort 2: Change From Baseline in CD4+ Cell Count at Week 24

Time frame: Baseline, Week 24

Cohort 2: Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline, Week 48

Cohort 3: Change From Baseline in CD4+ Cell Count at Week 24

Time frame: Baseline, Week 24

Cohort 3: Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline, Week 48

Cohort 1: Change From Baseline in CD4+ Cell Percentage at Week 24

Time frame: Baseline, Week 24

Cohort 1: Change From Baseline in CD4+ Cell Percentage at Week 48

Time frame: Baseline, Week 48

Cohort 2: Change From Baseline in CD4+ Cell Percentage at Week 24

Time frame: Baseline, Week 24

Cohort 2: Change From Baseline in CD4+ Cell Percentage at Week 48

Time frame: Baseline, Week 48

Cohort 3: Change From Baseline in CD4+ Cell Percentage at Week 24

Time frame: Baseline, Week 24

Cohort 3: Change From Baseline in CD4+ Cell Percentage at Week 48

Time frame: Baseline, Week 48

Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children

Overview

Conditions

Interventions

Eligibility

Locations (16)

Outcomes

Primary Outcomes

Secondary Outcomes