Clinical trial NCT03960645: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1-infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Study model 'single group' is selected as the Neonates group was only followed up but not treated.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC)
timeFrame: 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 outcomes:
measure: PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)
timeFrame: 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
measure: PK Parameter: AUClast of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: Cmax of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: Ctau of BIC and FTC
timeFrame: 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
measure: PK Parameter: Clast of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: Tmax of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: t1/2 of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: CLss/F of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: Vz/F of BIC, FTC, and TAF
timeFrame: 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
measure: PK Parameter: λz of BIC, FTC, and TAF
timeFrame: 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
measure: 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
timeFrame: At time of delivery
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates
timeFrame: At birth
Other outcomes:
Locations:
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virologics (IDEV)
city: Bangkok Noi
country: Thailand
facility: Faculty of Medicine Siriraj Hospital
city: Khon Kaen
country: Thailand
facility: Faculty of Medicine-Khon Kaen University
city: Mueang Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Diseases Institute
city: Mueang Nonthaburi
country: Thailand
facility: Research Institute for Health Sciences, Chiang Mai University
city: Pathumwan
country: Thailand
facility: Thai Red Cross AIDS Research Centre
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: