Evaluating the Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for HIV Prevention During Pregnancy and Postpartum

• Status: Recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

The purpose of this study is to evaluate the pharmacokinetics, feasibility, acceptability, and safety of a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as oral daily pre-exposure prophylaxis (PrEP) to prevent HIV during pregnancy and postpartum in adolescents and young women and their infants.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Gilead Sciences
• Treatments: Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir

Criteria

PK Component (Groups 1 and 2) Inclusion Criteria:

• At study entry, mother is 16-24 years of age.

• For mothers who are of legal age to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with site institutional review board (IRB)/ethics committee (EC) policies and procedures: The mother is willing and able to provide written informed consent for her and her infant's study participation.

• For mothers who are not of legal age to provide independent informed consent. The parent/guardian or other legally authorized representative of the mother and her infant is willing and able to provide written informed consent for the mother and her infant's study participation; in addition, when applicable the mother is willing and able to provide written assent for her and her infant's study participation.

• At screening, evidence of a viable singleton pregnancy (Group 1 only) with sonographic confirmation. Note: If adequate sonographic results are not available from medical records at screening, an ultrasound must be performed so that the result is available at study entry.

• At study entry, pregnant or recently delivered, in one of the following two enrollment windows:

• Group 1: Gestational age of 14 to 24 weeks, defined as greater than 13 weeks plus six days and less than 24 completed weeks of gestation with sonographic confirmation*, or

• Group 2: 6 to 12 weeks postpartum, defined as between 42 and 84 days after the date of delivery.

• *Note: If adequate sonographic results are not available from medical records at screening, an ultrasound must be performed so that the result is available at study entry.

• At study entry, willing to initiate once-daily oral PrEP and continue use for at least 12 weeks under directly observed therapy and support for adherence.

• Within 14 days prior to study entry, HIV negative by HIV RNA test.

• At study entry, rapid test negative and absence of symptoms of acute HIV infection (i.e. acute viral illness).

• At screening, Hepatitis B negative by Hepatitis B surface antigen test.

• At screening, has the following laboratory test results:

• Grade 1 or normal (less than 2.5 x upper limit of normal [ULN]) alanine transaminase (ALT)

• Grade 1 or normal (greater than or equal to 9.5 g/dL) hemoglobin

• Grade 1 or normal (greater than or equal to 800 cells/mm^3) absolute neutrophil count (ANC)

• Normal (greater than or equal to 90 mL/min) estimated creatinine clearance (CrCl; Cockcroft-Gault formula)

• At screening, mother has negative or trace proteinuria (less than Grade 1).

• At screening, mother has normal dipstick urine for glucose (less than Grade 1).

• At study entry, mother weighs greater than 35 kg.

• Intention to stay within the study site's catchment area for at least 12 weeks (or through delivery).

Exclusion Criteria (PK Component and PrEP Comparison Component):

• Mother has any current significant uncontrolled, active or chronic disease process that, in the judgment of the site investigator, would make participation in the study inappropriate.

• Mother has a known history of any of the following, as determined by the site investigator or designee based on maternal report and available medical records:

• Sickle cell anemia (excluding sickle cell trait), chronic bleeding, blood transfusion within the past 120 days (excluding for chronic illness) or other blood dyscrasias

• Bone fracture not explained by trauma

• Allergy/sensitivity to FTC/TDF or its components

• Fetus has a known or suspected major congenital anomaly, from chart review of prior data, defined as a structural malformation with surgical, medical, or cosmetic importance

• Mother has confirmed renal insufficiency, a history of known renal parenchymal disease, or known single kidney at screening

• Current use of prohibited medications listed in the protocol

• Concurrent participation in a study of any biomedical HIV prevention intervention or investigational drug in an HIV vaccine study or microbicide study

• Past participation in an HIV vaccine study

• Currently taking a PrEP regimen from non-study sources

• Any other condition or adverse social situation that, in the opinion of the site investigator, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

• Past participation in IMPAACT 2009

PrEP Comparison Component (Cohorts 1 and 2) Inclusion Criteria:

• At study entry, mother is 16-24 years of age.

• For mothers who are of legal age to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: The mother is willing and able to provide written informed consent for her and her infant's study participation.

• For mothers who are not of legal age to provide independent informed consent. The parent/guardian or other legally authorized representative of the mother and her infant is willing and able to provide written informed consent for the mother and her infant's study participation; in addition, when applicable the mother is willing and able to provide written assent for her and her infant's study participation.

• At screening, evidence of a viable singleton pregnancy with gestational age of 32 weeks or less, defined as 224 days or less after the date of conception with sonographic confirmation. Note: if adequate sonographic results are not available from medical records at screening, an ultrasound must be performed in the interim so that the result is available at study entry.

• Within 14 days prior to study entry, negative by HIV RNA test.

• At study entry, HIV rapid test negative and absence of symptoms of acute HIV infection (i.e. acute viral illness).

• At screening, Hepatitis B negative by Hepatitis B surface antigen test performed.

• At screening, has the following laboratory test results:

• Grade 1 or normal (less than 2.5 x ULN) ALT

• Grade 1 or normal (greater than or equal to 9.5 g/dL) HB

• Grade 1 or normal (greater than or equal to 800 cells/mm^3) ANC

• Normal (greater than or equal to 90 mL/min) for estimated creatinine clearance (CrCl; Cockcroft-Gault formula)

• At screening, mother has negative or trace proteinuria (less than Grade 1).

• At screening, mother has normal dipstick urine for glucose (less than Grade 1).

• Intention to stay within the study site's catchment area through 26 weeks postpartum

• Regular access to a cellular phone that is able to receive short message service (SMS) messages, and for Cohort 1 only, is also able to send SMS messages.

• Cohort 1 only: At study entry, expresses willingness to take PrEP from pregnancy up to 26 weeks postpartum

• Cohort 2 only: At study entry, expresses unwillingness to take PrEP from pregnancy up to 26 weeks postpartum

• At study entry, mother weighs greater than 35 kg

• Based on site investigator assessment at screening, mother is literate in one or more of the study languages