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

HIV-1 Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02285114
• Other study ID #: GS-US-311-1269
• Secondary ID: 2015-001339-19
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: January 20, 2015
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: December 2024
• Est. primary completion date: November 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

Key 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 ß-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.

Related Conditions & MeSH terms

• HIV-1

Intervention

Drug:
• F/TAF
F/TAF tablets administered orally once daily
• 3rd ARV agent
A 3rd antiretroviral (ARV) agent of the participant's pre-existing regimen may include one of the following: boosted atazanavir (ATV), boosted lopinavir (LPV), boosted darunavir (DRV), unboosted efavirenz (EFV), unboosted nevirapine (NVP), unboosted raltegravir (RAL), or unboosted dolutegravir (DTG).
• Boosted PIs
Boosted PIs of the participant's pre-existing regimen may include one of the following: ATV, LPV, or DRV.

Locations

Country	Name	City	State
Panama	Hospital del Nino	Panama City
South Africa	Be Part Yoluntu Centre	Cape Town
South Africa	KIDCRU, Ward J8, Tygerberg Children's Hospital	Cape Town
South Africa	Rahima Moosa Mother and Child Hospital	Johannesburg	Coronationville
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of California Los Angeles	Los Angeles	California
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Panama,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).	Any time at Week 2 visit
Primary	PK Parameter (Cohort 2): AUCtau of TAF	AUCtau is defined as concentration of drug over time (the area under the 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
Primary	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	PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV	Cmax is defined as the maximum concentration of drug.	Any time at Week 2 visit
Secondary	PK Parameter (Cohort 2): Cmax of TAF, FTC, and TFV	Cmax is defined as the maximum concentration of drug.	Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Secondary	PK Parameter (Cohort 1): Clast of TAF	Clast is defined as the last observable concentration of drug.	Any time at Week 2 visit
Secondary	PK Parameter (Cohort 2) : Clast of TAF	Clast is defined as the last observable concentration of drug.	Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Secondary	PK Parameter (Cohort 1): CL/F of TAF	CL/F is defined as the apparent oral clearance following administration of the drug.	Any time at Week 2 visit
Secondary	PK Parameter (Cohort 2): CL/F of TAF	CL/F is defined as the apparent oral clearance following administration of the drug.	Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Secondary	PK Parameter (Cohort 1): Vz/F of TAF	Vz/F is defined as the apparent volume of distribution of the drug.	Any time at Week 2 visit
Secondary	PK Parameter (Cohort 2): Vz/F of TAF	Vz/F is defined as the apparent volume of distribution of the drug.	Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Secondary	PK Parameter (Cohort 1): AUCtau of FTC and TFV	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).	Any time at Week 2 visit
Secondary	PK Parameter (Cohort 2): AUCtau of FTC and TFV	AUCtau is defined as concentration of drug over time (the area under the 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
Secondary	PK Parameter (Cohort 1): Ctau of FTC and TFV	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Any time at Week 2 visit
Secondary	PK Parameter (Cohort 2): Ctau of FTC and TFV	Ctau is defined as the observed drug concentration at the end of 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
Secondary	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.	Baseline through Week 48
Secondary	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.	Week 24
Secondary	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.	Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 24		Baseline, Week 24
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline, Week 48
Secondary	Change From Baseline in CD4 Percentage at Week 24		Baseline, Week 24
Secondary	Change From Baseline in CD4 Percentage at Week 48		Baseline, Week 48
Secondary	Percentage of Participants With Palatability of F/TAF Formulation	Palatability was reported based on the product taste of being normal or abnormal. Missing data were reported separately.	Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2)
Secondary	Percentage of Participants With Acceptability of F/TAF Formulation	Acceptability was reported based on the the product size and shape. Missing data were reported separately.	Baseline up to Week 4

External Links

•   Gilead Clinical Trials Website