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
• Last Update Posted: September 9, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

There will be 3 cohorts in this study.

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) single tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of E/C/F/TAF STR through Week 24 (Part B) in 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 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1 (12 to < 18 years of age); Participants within the ages of 12 and <18 years old will receive E/C/F/TAF STR once daily with food.	Drug: E/C/F/TAF; E/C/F/TAF tablets contain 150 mg of elvitegravir (EVG), 150 mg of cobicistat (COBI), 200 mg of emtricitabine (FTC), and 10 mg of tenofovir alafenamide (TAF; as 11.2 mg of TAF fumarate)
Experimental: Cohort 2 (6 to < 12 years of age); Participants within the ages of 6 and <12 years old and weighing ≥ 25 kg will receive E/C/F/TAF STR once daily with food.	Drug: E/C/F/TAF; E/C/F/TAF tablets contain 150 mg of elvitegravir (EVG), 150 mg of cobicistat (COBI), 200 mg of emtricitabine (FTC), and 10 mg of tenofovir alafenamide (TAF; as 11.2 mg of TAF fumarate)
Experimental: Cohort 3 (≥ 2 years of age); Participants ≥ 2 years of age and weighing ≥ 14 to < 25 kg will receive E/C/F/TAF STR once daily with food.	Drug: E/C/F/TAF (Low Dose); 90/90/120/6 mg STR administered orally

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetic (PK) Parameter: AUCtau for EVG (Part A of Cohort 1,2; Cohort 3) [ Time Frame: Predose and up to 24 hours postdose ]
   AUCtau is defined as concentration of drug over a dosing interval.
2. PK Parameter: AUClast for TAF (Part A of Cohort 1 and 2) [ Time Frame: Predose and up to 24 hours postdose ]
   AUClast is defined as the concentration of drug from time zero to the last observable concentration.
3. Incidence of Treatment-Emergent Serious Adverse Events [ Time Frame: Up to 24 weeks ]
4. Incidence of All Treatment-Emergent Adverse Events [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :

1. Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 24 ]
2. Percentage of Participants with Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 48 ]
3. Percentage of Participants with Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 24 ]
4. Percentage of Participants with Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis (Part B) [ Time Frame: Week 48 ]
5. Change from Baseline in Plasma log10 HIV-1 RNA (copies/mL) at Week 24 [ Time Frame: Baseline; Week 24 ]
6. Change from Baseline in Plasma log10 HIV-1 RNA (copies/mL) at Week 48 [ Time Frame: Baseline; Week 48 ]
7. Change from Baseline in CD4+ Cell Count (cells/μL) at Week 24 [ Time Frame: Baseline; Week 24 ]
8. Change from Baseline in CD4+ Cell Count (cells/μL) at Week 48 [ Time Frame: Baseline; Week 48 ]
9. Percentage Change from Baseline in CD4+ Cell Count (cells/μL) at Week 24 [ Time Frame: Baseline; Week 24 ]
10. Percentage Change from Baseline in CD4+ Cell Count (cells/μL) at Week 48 [ Time Frame: Baseline; Week 48 ]
11. PK Parameter: Ctau for EVG, FTC, TFV, and COBI (Part A) [ Time Frame: Predose and up to 24 hours postdose ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.
12. PK Parameter: Cmax for EVG, TAF, FTC, TFV, and COBI (Part A) [ Time Frame: Predose and up to 24 hours postdose ]
    Cmax is defined as the maximum concentration of drug.
13. PK Parameter: Apparent CL for EVG and TAF (Part A) [ Time Frame: Predose and up to 24 hours postdose ]
    Apparent clearance (CL) is defined as the systemic clearance of the drug following oral administration.
14. PK Parameter: Apparent Vz for EVG and TAF (Part A) [ Time Frame: Predose and up to 24 hours postdose ]
    Apparent Vz is defined as the apparent volume of distribution of the drug after oral administration.
15. PK Parameter: AUCtau for FTC, TFV, and COBI (Part A) [ Time Frame: Predose and up to 24 hours postdose ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years and older (Child, Adult, Older Adult)
• 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 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• 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
• Last Update Posted: September 9, 2020
• Last Verified: September 2020

• 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:

HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immune System Diseases; Slow Virus Diseases