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

• ClinicalTrials.gov Identifier: NCT03960645
• Recruitment Status: Recruiting
• First Posted: May 23, 2019
• Last Update Posted: January 8, 2021
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: May 21, 2019
• First Posted Date: May 23, 2019
• Last Update Posted Date: January 8, 2021
• Actual Study Start Date: June 28, 2019
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2019)

Pharmacokinetic (PK) Parameter: AUCtau of BIC [ Time Frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose ]

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 21, 2019)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetic, Safety, and Efficacy of B/F/TAF in 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1-infection

Intervention

Drug: B/F/TAF

50/200/25 mg FDC tablet administered orally once daily without regard to food

Study Arms

Experimental: B/F/TAF

B/F/TAF for up to approximately 38 weeks

Intervention: Drug: B/F/TAF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 21, 2019): 35
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2022
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: Dominican Republic, Puerto Rico, Thailand, United States

Administrative Information

• NCT Number: NCT03960645
• Other Study ID Numbers: GS-US-380-5310
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: January 2021