Study to Evaluate the Pharmacokinetics (PK), Safety, and Efficacy of B/F/TAF in Human Immunodeficiency Virus (HIV)-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters

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

The primary objective of this study is to evaluate the steady state PK 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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: B/F/TAF

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic, 10103
    • Instituto Dominicano de Estudios Virologics (IDEV)
• Thailand
  • Bangkok Noi, Thailand, 10700
    • Faculty of Medicine Siriraj Hospital
  • Khon Kaen, Thailand, 40002
    • Faculty of Medicine-Khon Kaen University
  • Mueang Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute
  • Mueang Nonthaburi, Thailand, 50200
    • Research Institute for Health Sciences, Chiang Mai University
  • Pathumwan, Thailand, 10330
    • Thai Red Cross Aids Research Centre
• United States
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 ribonucleic acid (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
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B/F/TAF; Pregnant women participants will receive fixed dose combination (FDC) tablet of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum).	Drug: B/F/TAF; 50/200/25 mg FDC tablet administered orally once daily without regard to food.; Other Names: GS-9883/F/TAF, Biktarvy®, BVY
No Intervention: Neonates; Neonates who will be born to women participants in the study will be followed from birth up to 8 weeks of age after obtaining consent from the parent or legal guardian. None of the neonates that participate in the study will be treated with the study drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC)	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum

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).	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: AUClast of BIC, FTC, and TAF	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: Cmax of BIC, FTC, and TAF	Cmax is defined as the maximum observed concentration of drug during the dosing interval.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: Ctau of BIC and FTC	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: Clast of BIC, FTC, and TAF	Clast is defined as the last observable concentration of drug.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: Tmax of BIC, FTC, and TAF	Tmax is defined as the time (observed time point) of Cmax.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
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.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: CLss/F of BIC, FTC, and TAF	CLss/F is defined as the apparent steady-state oral clearance following administration of the drug.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
PK Parameter: Vz/F of BIC, FTC, and TAF	Vz/F is defined as the apparent volume of distribution of the drug.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
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.	Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at the Time of Delivery Using the Missing = Excluded Approach in B/F/TAF Group	The percentage of participants with HIV-1 RNA < 50 copies/mL at the time of delivery was analyzed in B/F/TAF group using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation).	At time of delivery
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates	The percentage of participants with HIV-1 RNA < 50 copies/mL at the time of birth was analyzed in neonates using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation).	At birth

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2019
• Primary Completion (Actual): July 21, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: May 21, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): June 14, 2024
• Last Update Submitted That Met QC Criteria: June 4, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-380-5310; 2021-001073-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No