Pharmacokinetic, Safety, and Efficacy of B/F/TAF in HIV-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the steady state pharmacokinetics of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed pregnant women in their second and third trimesters.

Official Title
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A Phase 1b, Open-label Study to Evaluate the PK, Safety and Efficacy of B/F/TAF in HIV-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures With singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening Agree not to breastfeed for the duration of the study Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit Documented plasma HIV-1 RNA levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the screening visit Have no documented or suspected resistance to FTC, Tenofovir (TFV), or integrase strand-transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I Historic genotype reports will be collected if available Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta Normal maternal alfa-fetoprotein level at the screening visit Key Exclusion Criteria: Have chronic hepatitis B virus (HBV) Have active hepatitis C virus (HCV) infection An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B/F/TAF<br>B/F/TAF for up to approximately 38 weeks | Drug: B/F/TAF<br>* 50/200/25 mg FDC tablet administered orally once daily without regard to food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: AUCtau of BIC | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameter: AUCtau of emtricitabine (FTC) and tenofovir alafenamide (TAF) | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: AUClast of BIC, FTC, and TAF | AUClast is defined as the concentration of drug from time zero to the last observable concentration. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: Cmax of BIC, FTC, and TAF | Cmax is defined as the maximum observed concentration of drug during the dosing interval. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: Ctau of BIC and FTC | Ctau is defined as the observed drug concentration at the end of the dosing interval. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: Clast of BIC, FTC, and TAF | Clast is defined as the last observable concentration of drug. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: Tmax of BIC, FTC, and TAF | Tmax is defined as the time (observed time point) of Cmax. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: t1/2 of BIC, FTC, and TAF | t1/2 is defined as the estimate of the terminal elimination half-life of the drug. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: CL/F of BIC, FTC, and TAF | CL/F is defined as the apparent oral clearance following administration of the drug. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: Vz/F of BIC, FTC, and TAF | Vz/F is defined as the apparent volume of distribution of the drug. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| PK Parameter: λz of BIC, FTC, and TAF | λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. | Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| Proportion of Participants With HIV-1 RNA < 50 Copies/mL Using the Missing = Excluded Approach |  | At the Time of Delivery |