Pharmacokinetic, Safety, and Efficacy of B/F/TAF in 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 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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic, 10103
    • Instituto Dominicano de Estudios Virologics (IDEV)
• Puerto Rico
  • San Juan, Puerto Rico, 00925
    • Maternal Infant Studies Center (CEMI)
• Thailand
  • Bangkok Noi, Thailand, 10700
    • Faculty of Medicine Siriraj Hospital
  • Khon Kaen, Thailand, 40002
    • Faculty of Medicine-Khon Kaen University
  • Muang, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute
  • Muang, Thailand, 50200
    • Research Institute for Health Sciences, Chiang Mai University
  • Pathumwan, Thailand, 10330
    • Thai Red Cross Aids Research Centre
• United States
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's & Women's Hospital Long Beach
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Tampa, Florida, United States, 33762
      • University of South Florida
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System

Participation Criteria

Eligibility Criteria

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

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 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 20, 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): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 14, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-380-5310

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/
• 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