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 Sciences

Status and phase: Completed; Phase 3; Phase 2

Conditions: Acquired Immune Deficiency Syndrome (AIDS); HIV Infections

Treatments: Drug: E/C/F/TAF (Low Dose); Drug: E/C/F/TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT01854775

GS-US-292-0106

2013-002780-26 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 129 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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129 participants in 3 patient groups

Cohort 1: Age 12 to < 18 Years and Weight ≥ 35 kg

Experimental group

Description:

Treatment naive adolescents (12 to \< 18 years of age) living with human immunodeficiency virus (HIV) 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.

Treatment:

Drug: E/C/F/TAF

Cohort 2: Age 6 to < 12 Years and Weight ≥ 25 kg

Experimental group

Description:

Children (6 to \< 12 years of age weighing ≥ 25 kg) with HIV who were virologically suppressed 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.

Treatment:

Drug: E/C/F/TAF

Cohort 3: Age ≥2 Years and Weight ≥ 14 to <25 kg

Experimental group

Description:

Children (≥ 2 years of age weighing ≥ 14 to \< 25 kg) with HIV who were virologically suppressed 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 administered orally, once daily with food. 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.

Treatment:

Drug: E/C/F/TAF (Low Dose)

Drug: E/C/F/TAF