Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide Fixed Dose Combination in Adolescents and Children With Human Immunodeficiency Virus-1

Gilead Sciences

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: HIV-1 Infection

Treatments: Drug: B/F/TAF (Adult Strength); Drug: B/F/TAF (TOS); Drug: B/F/TAF (Low Dose)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02881320

2016-002345-39 (EudraCT Number)

GS-US-380-1474

Details and patient eligibility

About

The goals of this clinical study are to learn how Bictegravir/Emtricitabine/Tenofovir Alafenamide fixed dose combination (FDC) interacts with the body, confirm the dose, and also to learn more about the safety and tolerability of Bictegravir/Emtricitabine/Tenofovir Alafenamide FDC in adolescents and children with HIV-1.

Enrollment: 177 patients

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Cohort 1: HIV-1 infected adolescents (12 to < 18 years of age and screening weight ≥ 35 kg) who are virologically suppressed for ≥ 6 months prior to screening. Cohort 2: HIV-1 infected children (6 to < 12 years of age and screening weight ≥ 25 kg) who are virologically suppressed for ≥ 6 months prior to screening.

Cohort 3: HIV-1 infected children (≥ 2 years of age and screening weight of ≥ 14 to < 25 kg) who are virologically suppressed for ≥ 6 months prior to screening.

Cohort 4 Group 1: HIV-1 infected children (≥ 2 years of age and screening weight of ≥ 14 to < 25 kg) who are virologically suppressed for ≥ 6 months prior to screening and unable to swallow tablets.

• Documented plasma HIV-1 ribonucleic acid (RNA) < 50 copies/mL on a stable regimen (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 6 months preceding the Screening visit. Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests.
• Stable antiretroviral regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third agent for a minimum of 6 months prior to the screening visit. Individuals undergoing dose modifications to their antiretroviral regimen for growth or who are switching medication formulation(s) are considered to be on a stable antiretroviral regimen.
• Estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m^2 according to the Schwartz Formula.
• No documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), or integrase strand transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R and M184V/I.

Cohort 4 Group 2-4: HIV-1 infected children (≥ 1 month of age and screening weight of ≥ 3 to < 14 kg) who are treatment naive or on antiretroviral (ARV) treatment for ≥ 1 month prior to screening.

• Positive confirmatory HIV test (confirmatory nucleic acid-based testing if < 18 months of age).

• On a stable ARV regimen for ≥ 1 month or treatment naive (Individual is considered treatment naive if ARVs were given for prevention of mother-to-child transmission but not for HIV treatment).

• For < 1 year of age, eGFR ≥ the minimum normal values for age according to the information below using the Schwartz Formula,

  • 30 mL/min/1.73 m^2 for age > 4 weeks to ≤ 95 days.
  • 39 mL/min/1.73 m^2 for age ≥ 96 days to ≤ 6 months.
  • 49 mL/min/1.73 m^2 for age > 6 months to < 12 months.

• For ≥ 1 year of age, eGFR ≥ 90 mL/min/1.73 m^2 using the Schwartz Formula.

• No documented or suspected resistance to FTC, TFV, or INSTIs including, but not limited to, the reverse transcriptase resistance mutation K65R.

• For individuals < 14 kg, M184V/I AND HIV-1 RNA < 50 copies/mL will be allowed. Individuals with HIV-1 RNA > 50 copies/mL should not have FTC, TFV, or INSTI resistance mutations.

• Last dose of nevirapine (NVP) or efavirenz (EFV), if applicable, ≥ 14 days prior to enrollment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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177 participants in 8 patient groups

Cohort 1 (12 to < 18 years of age and weight ≥ 35 kg)

Experimental group

Description:

* Part A: Participants will participate in an Intensive PK evaluation at Week 2 or Week 4 and continue to receive the adult strength B/F/TAF FDC through Week 48. * Part B: Following confirmation of BIC PK data from Cohort 1 Part A, participants will receive the adult strength B/F/TAF through Week 48.

Treatment:

Drug: B/F/TAF (Adult Strength)

Cohort 2 (6 to < 12 years of age and weight ≥ 25 kg)

Experimental group

Description:

* Part A: Participants will participate in an Intensive PK evaluation at Week 2 or Week 4 and continue to receive the adult strength B/F/TAF FDC through Week 48. * Part B: Following confirmation of BIC PK data from Cohort 2 Part A, participants will receive the adult strength B/F/TAF FDC through Week 48.

Treatment:

Drug: B/F/TAF (Adult Strength)

Cohort 3 (≥ 2 years of age and weight ≥ 14 to < 25 kg)

Experimental group

Description:

* Part A: Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive the low dose B/F/TAF FDC tablet through Week 48. * Part B: Following confirmation of BIC PK data from Cohort 3 Part A, participants will receive the low dose B/F/TAF FDC tablet through Week 48.

Treatment:

Drug: B/F/TAF (Low Dose)

Cohort 4 Group 1 (≥ 2 years of age and weight ≥ 14 to < 25 kg)

Experimental group

Description:

Due to Cohort 3 Part A Intensive PK evaluation at Week 2 with the low dose B/F/TAF FDC tablet, participants will not participate in an Intensive PK evaluation at Week 2. Participants will receive B/F/TAF FDC tablets for oral suspension (TOS) once daily through Week 48.

Treatment:

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Cohort 4 Group 2 (≥ 1 month of age and weight ≥ 10 to < 14 kg)

Experimental group

Description:

Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive B/F/TAF FDC TOS twice daily through Week 48.

Treatment:

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Cohort 4 Group 3 (≥ 1 month of age and weight ≥ 6 to < 10 kg)

Experimental group

Description:

Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive B/F/TAF FDC TOS twice daily through Week 48.

Treatment:

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Cohort 4 Group 4 (≥ 1 month of age and weight ≥ 3 to < 6 kg)

Experimental group

Description:

Participants will participate in an Intensive PK evaluation at Week 2 after which they will continue to receive B/F/TAF FDC TOS twice daily through Week 48.

Treatment:

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Open-Label Extension

Experimental group

Description:

Following Week 48, participants in countries where B/F/TAF is not available may have the option to receive adult strength B/F/TAF FDC, low dose B/F/TAF FDC, or B/F/TAF FDC TOS (based on age and weight) until it becomes available for use according to the participant's age and weight or the product becomes accessible to participants through an access program.

Treatment:

Drug: B/F/TAF (Low Dose)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (TOS)

Drug: B/F/TAF (Adult Strength)