The purpose of this study is to evaluate the steady state pharmacokinetics 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.
- Conditions
- Human Immunodeficiency Virus (HIV-1) InfectionsMedDRA version: 20.1Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2021-001073-23-Outside-EU/EEA
- Lead Sponsor
- Gilead Sciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- Female
- Target Recruitment
- Not specified
Participants must meet all of the following inclusion criteria to be eligible for participation in this study.
1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
2) Female participants of age = 18 to < 40 years with singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening
3) Agree not to breastfeed for the duration of the study
4) Currently on a stable antiretroviral regimen for = 6 months preceding the screening visit
5) 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
a) In the preceding 6 months prior to screening, one episode of blip” (HIV-1 RNA = 50 copies/mL and < 400 copies/mL) is acceptable, only if HIV-1 RNA is < 50 copies/mL immediately before and after the blip
b) To determine virologic suppression in the preceding 6 months prior to screening, the lower limit of quantification (LLOQ) by the local HIV-1 RNA assay may be used, only if its LLOQ is greater than 50 copies/mL (e.g.
LLOQ of 75 copies/mL)
6) Have no documented or suspected resistance to FTC, TFV, or INSTIs including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I.
a) Historic genotype reports will be collected if available
7) 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
8) Normal maternal alfa-fetoprotein level at the Screening Visit
9) Estimated glomerular filtration rate (eGFR) = 90 mL/min according to the Cockcroft-Gault (C-G) formula {Cockcroft 1976}:
(140 – age in years) X (wt in kg) / 72 X (serum creatinine in mg/dL) X 0.85 = CLcr (mL/min)
(140 – age in years) x (wt in kg) x 0.85 / 72 x (serum creatinine in umol/L) x 0.6786 = CLcr (mL/sec)
10) Normal ECG (or if abnormal, determined by the investigator not to be clinically significant)
11) Hepatic transaminases (AST and ALT) = 5 x upper limit of normal (ULN)
12) Total bilirubin = 1.5 mg/dL (= 26 umol/L), or normal direct bilirubin
13) Adequate hematologic function (absolute neutrophil count = 750/mm3 (= 0.75 GI/L); platelets = 50,000/mm3 (= 50 GI/L); hemoglobin = 9.5 g/dL (= 95 g/L))
14) Serum amylase = 5 × ULN (participants with serum amylase > 5 × ULN will remain eligible if serum lipase is = 5 × ULN)
15) Participants of childbearing potential must agree to utilize protocol recommended highly effective contraceptive methods or be non-heterosexually active or practice sexual abstinence (as defined in Appendix 6) during the post-partum period of the study, and for 7 days following the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Participants who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Have chronic hepatitis B virus (HBV) as determined by either:
a) Positive HBV surface antigen (HBsAg) at the Screening Visit
b) Negative HBV surface antigen, negative HBV surface antibody, positive HBV core antibody and quantifiable HBV DNA (HBV DNA = 20 IU/mL) at
the Screening Visit
2) Have active hepatitis C virus (HCV) infection
a) Positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable
3) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening (refer to Appendix 5)
4) Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
5) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (e.g, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
6) Malignancy within 5 years of screening other than cutaneous Kaposi’s sarcoma, completely resected non-melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). A prior malignancy treated with curative therapy and for which there has been no evidence of disease for at least five years prior to screening is allowed.
7) Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance
8) Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal therapy within 30 days prior to Day 1
9) Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
10) Any other clinical condition, including pregnancy complications such as gestational diabetes or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements
11) Active tuberculosis infection
12) Known hypersensitivity to B/F/TAF, their metabolites, or formulation excipient.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the steady state pharmacokinetics (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 the second and third trimesters of pregnancy;Secondary Objective: • To evaluate the steady state PK of emtricitabine (FTC) and TAF in the second and third trimesters of pregnancy<br>• To evaluate maintenance of HIV-1 virologic suppression in pregnant women receiving the B/F/TAF FDC during the second and/or third trimesters;Primary end point(s): The primary endpoint is the PK parameter AUCtau of BIC during the second and/or third trimesters through post-partum.;Timepoint(s) of evaluation of this end point: Intensive PK (iPK) visits during second and/or third trimesters through post-partum with sample collection timepoints as follows: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • The PK parameter AUCtau for FTC and TAF, and PK parameters AUClast, Cmax, Ctau, Clast, Tmax, T1/2, CL/F, Vz/F and ?z for BIC, FTC and TAF, as applicable<br>• The proportion of participants with plasma HIV-1 RNA < 50 copies/mL at the time of delivery by missing = excluded approach.;Timepoint(s) of evaluation of this end point: - Intensive PK (iPK) visits during second and/or third trimesters through post-partum with sample collection timepoints as follows: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose<br>- At the delivery visit<br>