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

• ClinicalTrials.gov Identifier: NCT01854775
• Recruitment Status: Active, not recruiting
• First Posted: May 16, 2013
• Results First Posted: May 24, 2021
• Last Update Posted: June 30, 2022
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

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 in virologically suppressed HIV-1 infected children 6 to < 12 years of age weighing ≥ 25 kg administered E/C/F/TAF STR (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 in virologically suppressed HIV-1 infected children 6 to < 12 years of age weighing ≥ 25 kg (Part B).

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.

Condition or disease	Intervention/treatment	Phase
Acquired Immune Deficiency Syndrome (AIDS); HIV Infections	Drug: E/C/F/TAF; Drug: E/C/F/TAF (Low Dose)	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 129 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3, Open-Label Study of 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
• Actual Study Start Date: May 6, 2013
• Actual Primary Completion Date: May 11, 2020
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg; HIV-infected, ARV treatment-naive adolescents (12 to < 18 years of age weighing ≥ 35 kg) will receive E/C/F/TAF (150/150/200/10 mg) fixed-dose combination (FDC) once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.	Drug: E/C/F/TAF; Tablets administered orally with food.; Other Name: Genvoya®
Experimental: Cohort 2: Age 6 to < 12 Years and Weight ≥ 25 kg; Virologically suppressed HIV-infected children (6 to < 12 years of age weighing ≥ 25 kg) will receive E/C/F/TAF (150/150/200/10 mg) FDC once daily for 48 weeks. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF become commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.	Drug: E/C/F/TAF; Tablets administered orally with food.; Other Name: Genvoya®
Experimental: Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg; Virologically suppressed HIV-infected children (≥ 2 years of age weighing ≥ 14 to < 25 kg) will receive E/C/F/TAF (90/90/120/6 mg) FDC once daily for 48 weeks. Participants who attain a weight of ≥ 25 kg during the course of the study will switch to adult E/C/F/TAF (150/150/200/10 mg) tablets. Participants who complete 48 weeks of study treatment will have the option to receive E/C/F/TAF in an extension phase of the study until: a) the participant turns 18 years old and E/C/F/TAF is commercially available for adults in the country in which the participant is enrolled; b) age-appropriate E/C/F/TAF became commercially available in the country in which the participant is enrolled; or c) Gilead elects to terminate development of E/C/F/TAF in that country.	Drug: E/C/F/TAF; Tablets administered orally with food.; Other Name: Genvoya®; Drug: E/C/F/TAF (Low Dose); 90/90/120/6 mg STR administered once daily orally with food.

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG) (Cohort 1) [ 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 ]
   AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
2. PK Parameter: AUCtau of EVG (Cohort 2) [ 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 ]
   AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
3. PK Parameter: AUCtau of EVG (Cohort 3) [ 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 ]
   AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
4. PK Parameter: AUClast of Tenofovir Alafenamide (TAF) (Cohort 1) [ 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 ]
   AUClast is defined as the concentration of drug from time zero to the last observable concentration.
5. PK Parameter: AUClast of TAF (Cohort 2) [ 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 ]
   AUClast is defined as the concentration of drug from time zero to the last observable concentration.
6. PK Parameter: AUCtau of TAF (Cohort 3) [ 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 ]
   AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
7. Cohort 1: Percentage of Participants With All Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: From first dose date up to Week 24 ]

   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.
8. Cohort 2: Percentage of Participants With All Treatment-Emergent AEs and Treatment-Emergent SAEs [ Time Frame: From first dose date up to Week 24 ]

   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.
9. Cohort 3: Percentage of Participants With All Treatment-Emergent AEs and Treatment-Emergent SAEs [ Time Frame: From first dose date up to Week 24 ]

   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.

Secondary Outcome Measures :

1. PK Parameter: Ctau of EVG, FTC, TFV, and COBI (Cohort 1) [ 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 ]
   Ctau is defined as the observed drug concentration at the end of the dosing interval.
2. PK Parameter: Ctau of EVG, FTC, TFV, and COBI (Cohort 2) [ 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 ]
   Ctau is defined as the observed drug concentration at the end of the dosing interval.
3. PK Parameter: Ctau of EVG, FTC, TFV, and COBI (Cohort 3) [ 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 ]
   Ctau is defined as the observed drug concentration at the end of the dosing interval.
4. PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 1) [ 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 ]
   Cmax is defined as the maximum concentration of drug.
5. PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 2) [ 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 ]
   Cmax is defined as the maximum concentration of drug.
6. PK Parameter: Cmax of EVG, TAF, FTC, TFV, and COBI (Cohort 3) [ 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 ]
   Cmax is defined as the maximum concentration of drug.
7. PK Parameter: CL of EVG and TAF (Cohort 1) [ 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 ]
   Clearance (CL) is defined as the systemic clearance of the drug following intravenous administration.
8. PK Parameter: CL of EVG and TAF (Cohort 2) [ 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 ]
   Clearance (CL) is defined as the systemic clearance of the drug following intravenous administration.
9. PK Parameter: CL of EVG and TAF (Cohort 3) [ 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 ]
   Clearance (CL) is defined as the systemic clearance of the drug following intravenous administration.
10. PK Parameter: Vz of EVG and TAF (Cohort 1) [ 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 ]
    Vz is defined as the volume of distribution of the drug after intravenous administration.
11. PK Parameter: Vz of EVG and TAF (Cohort 2) [ 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 ]
    Vz is defined as the volume of distribution of the drug after intravenous administration.
12. PK Parameter: Vz of EVG and TAF (Cohort 3) [ 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 ]
    Vz is defined as the volume of distribution of the drug after intravenous administration.
13. PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 1) [ 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 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
14. PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 2) [ 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 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
15. PK Parameter: AUCtau of FTC, TFV, and COBI (Cohort 3) [ 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 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
16. Cohort 1: 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 ]
    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.
17. Cohort 1: 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 ]
    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.
18. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, as Defined by the FDA Snapshot Analysis [ Time Frame: Week 24 ]
    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.
19. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, as Defined by the FDA Snapshot Analysis [ Time Frame: Week 48 ]
    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.
20. 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 ]
    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.
21. 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 ]
    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.
22. 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 ]
    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.
23. 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 ]
    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.
24. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.
25. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed based on missing = failure analyses.
26. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Failure Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.
27. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Failure Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed based on missing = failure analyses.
28. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.
29. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed based on missing = failure analyses.
30. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Failure Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 was analyzed based on missing = failure analyses.
31. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Failure Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed based on missing = failure analyses.
32. Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Failure Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = failure analyses.
33. Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Failure Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed based on missing = failure analyses.
34. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = excluded analyses.
35. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed based on missing = excluded analyses.
36. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Excluded Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 was analyzed based on missing = excluded analyses.
37. Cohort 1: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Excluded Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed based on missing = excluded analyses.
38. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = excluded analyses.
39. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed based on missing = excluded analyses.
40. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24, Based on Missing = Excluded Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 was analyzed based on missing = excluded analyses.
41. Cohort 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48, Based on Missing = Excluded Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed based on missing = excluded analyses.
42. Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 24, Based on Missing = Excluded Analyses [ Time Frame: Week 24 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed based on missing = excluded analyses.
43. Cohort 3: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL at Week 48, Based on Missing = Excluded Analyses [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed based on missing = excluded analyses.
44. Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24 [ Time Frame: Baseline, Week 24 ]
45. Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Week 48 [ Time Frame: Baseline, Week 48 ]
46. Cohort 1: Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ]
47. Cohort 1: Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ]
48. Cohort 2: Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ]
49. Cohort 2: Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ]
50. Cohort 3: Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline, Week 24 ]
51. Cohort 3: Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline, Week 48 ]
52. Cohort 1: Change From Baseline in CD4+ Cell Percentage at Week 24 [ Time Frame: Baseline, Week 24 ]
53. Cohort 1: Change From Baseline in CD4+ Cell Percentage at Week 48 [ Time Frame: Baseline, Week 48 ]
54. Cohort 2: Change From Baseline in CD4+ Cell Percentage at Week 24 [ Time Frame: Baseline, Week 24 ]
55. Cohort 2: Change From Baseline in CD4+ Cell Percentage at Week 48 [ Time Frame: Baseline, Week 48 ]
56. Cohort 3: Change From Baseline in CD4+ Cell Percentage at Week 24 [ Time Frame: Baseline, Week 24 ]
57. Cohort 3: Change From Baseline in CD4+ Cell Percentage at Week 48 [ Time Frame: Baseline, Week 48 ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Cohort 1

  • 12 years to < 18 years of age at baseline
  • Weight greater than or equal to 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, FTC and tenofovir (TFV)
  • No prior use of any approved or experimental anti-HIV-1 drug for any length of time

• Cohort 2

  • 6 years to < 12 years of age at baseline
  • Weight greater than or equal to 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.

Contacts and Locations

Locations

United States, California

Miller's Children Hospital

Long Beach, California, United States, 90806

United States, District of Columbia

Children's Research Institute

Washington, District of Columbia, United States, 20010

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30322

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105-0371

South Africa

KIDCRU Ward J8

Cape Town, South Africa, 7505

Be Part Yoluntu Centre

Cape Town, South Africa, 7646

Desmond Tutu HIV Foundation

Cape Town, South Africa, 7705

Perinatal HIV Research Unit Baragwanath Hospital

Johannesburg, South Africa, 1862

Clinical HIV Research Unit

Johannesburg, South Africa, 2041

Empilweni Services and Research Unit (ESRU)

Johannesburg, South Africa, 2092

Thailand

The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)

Bangkok, Thailand, 10330

Queen Savang Vadhana Memorial Hospital

Chon Buri, Thailand, 20110

Department of Pediatrics, Faculty of Medicine, Khon Kaen University

Khon Kaen, Thailand, 40002

Uganda

Joint Clinical Research Centre

Kampala, Uganda, PO Box 10005

Zimbabwe

University of Zimbabwe - Clinical Research Centre

Belgravia, Zimbabwe, 263

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

  Study Documents (Full-Text)

Documents provided by Gilead Sciences:

Study Protocol  [PDF] February 21, 2020

Statistical Analysis Plan: Interim 4 Analysis  [PDF] October 12, 2018

Statistical Analysis Plan: Interim 6 Analysis  [PDF] November 25, 2020

More Information

Additional Information:

Gilead Clinical Trials Website 

Publications of Results:

Rakhmanina N, Gaur A, Natukunda E, Chokephaibulkit K, Liberty A, Kido A, et al. Acceptability and palatability of the single-tablet regimens of B/F/TAF and E/C/F/TAF in children (6-12 years) living with HIV infection [Abstract 33]. 10th International Workshop on HIV Pediatrics; 2018 July 21-22; Amsterdam, The Netherlands

Sharma S, Gupta S, Majeed S, Strehlau R, Hellstrom E, Liu Y, et al. Exposure-Safety of Tenofovir in Pediatric HIV-Infected Participants: Comparison of Tenofovir Alafenamide & Tenofovir Disoproxil Fumarate [Abstract 23]. 10th International Workshop on HIV Pediatrics; 2018 July 21-22; Amsterdam, The Netherlands.

Natukunda E, Gaur AH, Kosalaraksa P, Batra J, Rakhmanina N, Porter D, Shao Y, Zhang H, Pikora C, Rhee MS. Safety, efficacy, and pharmacokinetics of single-tablet elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed, HIV-infected children: a single-arm, open-label trial. Lancet Child Adolesc Health. 2017 Sep;1(1):27-34. doi: 10.1016/S2352-4642(17)30009-3. Epub 2017 Jun 29.

Rakhmanina N, Natukunda E, Kosalaraksa P, Batra J, Gaur A, Shao Y, et al. Safety and efficacy of E/C/F/TAF in virologically suppressed, HIV-infected children through 48 weeks [Abstract 32]. 9th International Workshop on HIV Pediatrics; 2017 July 21-22; Paris, France.

Gaur A, Natukunda E, Kosalarksa P, Batra J, Rakhmanina N, Coluci A, et al. Pharmacokinetics, Safety, and Efficacy of E/C/F/TAF in HIV-1-Infected Children (6 to <12 years) [Poster 424]. Conference on Retroviruses and Opportunistic Infections (CROI); 2017 February 13-16; Seattle Washington.

Gaur AH, Kizito H, Prasitsueubsai W, Rakhmanina N, Rassool M, Chakraborty R, Batra J, Kosalaraksa P, Luesomboon W, Porter D, Shao Y, Myers M, Ting L, SenGupta D, Quirk E, Rhee MS. Safety, efficacy, and pharmacokinetics of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in treatment-naive, HIV-infected adolescents: a single-arm, open-label trial. Lancet HIV. 2016 Dec;3(12):e561-e568. doi: 10.1016/S2352-3018(16)30121-7. Epub 2016 Oct 17.

Gaur A, Kizito H, Chakraborty R, Batra J, Kosalaraksa P, Luesomboon W, et al. Safety and Efficacy of E/C/F/TAF in HIV-1 Infected Treatment-Naive Adolescents [Poster 817]. Conference on Retroviruses and Opportunistic Infections (CROI); 2016 February 22-25; Boston, Massachusetts.

Natukunda E, Liberty A, Strehlau R, Hellstrom E, Hakim JG, Kaur H, et al. Safety, pharmacokinetics and efficacy of low dose E/C/F/TAF in virologically suppressed children ≥ 2 years old living with HIV. (Abstract OABLB0101) 23rd International AIDS Conference; 06-10 July 2020 (Virtual).

Natukunda E, Liberty A, Strehlau R, Hellstrom E, Hakim J, Kaur H, et al. Safety, pharmacokinetics, and efficacy of low dose E/C/F/TAF in virologically suppressed children ≥ 2 years old living with HIV. (Abstract 3) International Workshop on HIV Pediatrics 2020; 16-17 November 2020 (Virtual).

Liberty A, Strehlau R, Rakhmanina N, Chokephaibulkit K, Koziara J, Kaur H, et al. Acceptability and palatability of low dose B/F/TAF and E/C/F/TAF in children (≥ 2y) with HIV. (Abstract 57) International Workshop on HIV Pediatrics 2020; 16-17 November 2020 (Virtual).

Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Lawson E, Shao Y, et al. Safety, Efficacy and Pharmacokinetics of the Integrase Inhibitor-Based E/C/F/TAF Single-Tablet Regimen in Treatment-Naïve HIV-Infected Adolescents Through 24 Weeks of Treatment [Poster 953]. Conference on Retroviruses and Opportunistic Infections; 2015 February 23-26; Seattle, WA.

Porter DP, Bennett SR, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs [Poster 952]. Conference on Retroviruses and Opportunistic Infections (CROI); 2015 23-26 February; Seattle, WA.

Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Lawson E, Shao Y, et al. Safety, Efficacy and Pharmacokinetics of the Integrase Inhibitor-Based E/C/F/TAF Single-Tablet Regimen in Treatment-Naïve HIV-Infected Adolescents Through 24 Weeks of Treatment [Poster 36]. 16th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy; 2015 26-28 May; Washington, DC.

Other Publications:

Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, et al. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) [Presentation #MOAB0104]. International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; 2015 19-22 July; Vancouver, Canada.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01854775
• Other Study ID Numbers: GS-US-292-0106; 2013-002780-26 ( EudraCT Number )
• First Posted: May 16, 2013
• Results First Posted: May 24, 2021
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:

Adolescents; HIV-1; HIV; Treatment-naive; Virologically suppressed

Additional relevant MeSH terms:

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immune System Diseases; Slow Virus Diseases; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents