Study of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Newborns Exposed to HIV
- Conditions
- HIV-1-infection
- Interventions
- Drug: B/F/TAF
- Registration Number
- NCT07055451
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this clinical study is to learn more about the study drug, Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), safety, tolerability, and pharmacokinetics (how B/F/TAF is absorbed, modified, distributed, and removed from the body of the participants) in neonates exposed to human immunodeficiency virus type 1 (HIV-1).
The primary objective of this study is to evaluate the safety and plasma pharmacokinetics (PK) (how B/F/TAF is absorbed, modified, distributed, and removed from the body of the participants) of B/F/TAF tablet for oral suspension (TOS) in full-term neonates exposed to HIV-1 but uninfected.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 16
Mother inclusion criteria:
- Be on standard of care (SOC) antiretroviral therapy for human immunodeficiency virus type 1 (HIV-1) treatment.
- Have confirmed HIV-1 infection based on positive test results obtained from medical records.
Neonate inclusion criteria:
- Be born at term (≥ 37.0 weeks gestational age).
- Be able to take oral medication.
- Be ≤ 120 hours of life at enrollment.
- Have a birth weight ≥ 2.5 kg.
- Is receiving or plans to receive HIV-1 SOC prophylaxis regimen with 1 antiretroviral (ARV) to prevent perinatal transmission.
Key
Mother exclusion criteria:
- Has a maternal-fetal blood group incompatibility identified by clinically relevant antibody that can cause hemolytic diseases of the neonate.
- Is breastfeeding or plans to breastfeed while on bictegravir (BIC) or emtricitabine (FTC) containing regimen. Mothers on BIC or FTC containing regimen, but not breastfeeding, can be enrolled in the study.
Neonate exclusion criteria:
- Had prior or expected to require blood exchange transfusion.
- Is receiving or plans to receive any component of B/F/TAF or dolutegravir as part of their SOC ARV prophylaxis regimen.
- Has a documented positive HIV-1 nucleic acid test.
- Has Grade 2 or higher aspartate aminotransferase, total bilirubin, hemoglobin, platelets or creatinine. Has Grade 1 or higher alanine aminotransferase.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: Group A of B/F/TAF B/F/TAF Full-term neonate participants, who are exposed to HIV-1 but uninfected, with a weight of ≥ 2.5 kg at birth and their mothers will be assigned to Cohort 1 Group A to evaluate a different pharmacokinetic (PK) sampling scheme than Cohort 1 Group B. Neonate participants will receive a single dose of B/F/TAF fixed-dose combination 1.88/7.5/0.94 mg tablet for oral suspension administered along with 1 antiretroviral as standard of care postnatal prophylaxis at both Visits 1 and 3. Cohort 1: Group B of B/F/TAF B/F/TAF Once enrollment in Cohort 1 Group A is completed, full-term neonate participants, who are exposed to HIV-1 but uninfected, with a weight of ≥ 2.5 kg at birth and their mothers will be assigned to Cohort 1 Group B to evaluate a different PK sampling scheme than Cohort 1 Group A. Participants will receive a single dose of B/F/TAF fixed-dose combination 1.88/7.5/0.94 mg tablet for oral suspension administered along with 1 antiretroviral as standard of care postnatal prophylaxis at both Visits 1 and 3.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAs) Though Week 8 After Neonate Birth First dose date up to 8 Weeks Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 8 After Neonate Birth First dose date up to 8 Weeks Pharmacokinetic (PK) parameters for Bictegravir (BIC): AUCinf Predose up to 72 hours postdose AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time.
PK parameters for BIC: AUClast Predose up to 72 hours postdose AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
PK parameters for BIC: AUC0-24h Predose up to 24 hours postdose AUC0-24h is defined as the partial area under the concentration versus time curve from time 0 to time 24 hours.
PK parameters for BIC: Cmax Predose up to 72 hours postdose Cmax is defined as the maximum observed concentration of drug.
PK parameters for BIC: Tmax Predose up to 72 hours postdose Tmax is defined as the time (observed time point) of Cmax.
PK parameters for BIC: Cmin Predose up to 72 hours postdose Cmin is defined as the minimum observed concentration of drug.
PK parameters for BIC: C24h At 24 hours postdose C24h is defined as the concentration of drug at time 24 hours.
PK parameters for BIC: t1/2 Predose up to 72 hours postdose t1/2 is defined as the terminal elimination half-life.
PK parameters for BIC: Apparent CL/F Predose up to 72 hours postdose Apparent CL/F is defined as the apparent total body clearance for extravascular administration.
PK parameters for BIC: Apparent Vz/F Predose up to 72 hours postdose Apparent Vz/F is defined as the apparent volume of distribution based on the terminal phase.
- Secondary Outcome Measures
Name Time Method PK Parameters for Emtricitabine (FTC), and Tenofovir (TFV): AUCinf Predose up to 72 hours, extrapolated to end of the dose and concentration time curve (AUCinfinity) AUCinf is defined as the area under the concentration versus time curve extrapolated to infinite time.
PK parameters for FTC, TAF, and TFV: AUClast Predose up to 72 hours postdose AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.
PK parameters for FTC, TAF, and TFV: AUC0-24h Predose up to 24 hours postdose AUC0-24h is defined as the partial area under the concentration versus time curve from time 0 to time 24 hours.
PK parameters for FTC, TAF, and TFV: Cmax Predose up to 72 hours postdose Cmax is defined as the maximum observed concentration of drug.
PK parameters for FTC, TAF, and TFV: Tmax Predose up to 72 hours postdose Tmax is defined as the time (observed time point) of Cmax.
PK parameters for FTC, TAF, and TFV: Cmin Predose up to 72 hours postdose Cmin is defined as the minimum observed concentration of drug.
PK parameters for FTC, TAF, and TFV: C24h At 24 hours postdose C24h is defined as the concentration of drug at time 24 hours.
PK parameters for FTC, TAF, and TFV: t1/2 Predose up to 72 hours postdose t1/2 is defined as the terminal elimination half-life.
PK parameters for FTC and TAF: Apparent CL/F Predose up to 72 hours postdose Apparent CL/F is defined as the apparent total body clearance for extravascular administration.
PK parameters for FTC and TAF: Apparent Vz/F Predose up to 72 hours postdose Apparent Vz/F is defined as the apparent volume of distribution based on the terminal phase.
Mother/Caregiver Reported Acceptability of B/F/TAF tablet for oral suspension (TOS) First dose date up to 15 days Acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better acceptability.
Mother/Caregiver Reported Palatability of B/F/TAF tablet for oral suspension (TOS) First dose date up to 15 days Palatability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability.