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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03960645
• Other study ID #: GS-US-380-5310
• Secondary ID: 2021-001073-23
• Status: Completed
• Phase: Phase 1
• Start date: June 28, 2019
• Est. completion date: August 18, 2022

Study information

• Verified date: December 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: August 18, 2022
• Est. primary completion date: July 21, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• B/F/TAF
50/200/25 mg FDC tablet administered orally once daily without regard to food.

Locations

Country	Name	City	State
Dominican Republic	Instituto Dominicano de Estudios Virologics (IDEV)	Santo Domingo
Thailand	Faculty of Medicine Siriraj Hospital	Bangkok Noi
Thailand	Faculty of Medicine-Khon Kaen University	Khon Kaen
Thailand	Bamrasnaradura Infectious Diseases Institute	Mueang Nonthaburi
Thailand	Research Institute for Health Sciences, Chiang Mai University	Mueang Nonthaburi
Thailand	Thai Red Cross AIDS Research Centre	Pathumwan
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Dominican Republic,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	PK Parameter: ?z of BIC, FTC, and TAF	?z 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
Secondary	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
Secondary	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