Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy

Official title

Phase IV Study of the Pharmacokinetics of Long-Acting Injectable Cabotegravir and Rilpivirine in Pregnant and Postpartum Women With HIV in the United States

Overview

Phase IV, multi-site, open-label, non-randomized study of the pharmacokinetics (PK) of long-acting injectable cabotegravir and rilpivirine (CAB LA + RPV LA) during pregnancy and postpartum.

Detailed description

Up to 40 adult-participants with HIV viral suppression will be enrolled, in pairs with their infants, to achieve 30 evaluable adult-participants overall. The study will include women who initiated CAB LA + RPV LA outside the study, prior to study entry, either pre-conception (including on the day of conception) or post-conception.

Interventions

• Drug Every 4-week long-acting injectable cabotegravir and rilpivirine
  Long-acting injectable cabotegravir and rilpivirine, initiated pre- or post-conception. Participants will receive these drugs as prescribed outside the study by their non-study clinical care provider

Primary outcome measures

• Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model [Time frame: Measured from study entry through six weeks postpartum]
• Geometric mean pharmacokinetic trough of CAB and RPV from every 4 week (Q4W) CAB LA and RPV LA measured every 4 weeks in plasma in second trimester, third trimester, and postpartum [Time frame: Measured from study entry through six weeks postpartum]

Secondary outcome measures (12)

• Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery [Time frame: Delivery]
• Percentage of adult participants with virologic escape [Time frame: Measured from study entry through six weeks postpartum]
• Percentage of adult participants with confirmed virologic failure [Time frame: Through 6 weeks postpartum]
• Number of adult participants with HIV resistance to CAB or RPV who had confirmed virologic failure [Time frame: Through 6 weeks postpartum]
• Number of infant participants with perinatal transmission [Time frame: Birth and six weeks post-birth]
• Percentage of adult participants with at least one Grade 3 or higher adverse event [Time frame: Measured from study entry through six weeks postpartum]
• Percentage of adult participants with at least one serious adverse event [Time frame: Measured from study entry through six weeks postpartum]
• Percentage of infant participants with at least one serious adverse event [Time frame: Measured from birth through six weeks post-birth]
• Percentage of adult participants with spontaneous abortion [Time frame: Through 6 weeks postpartum]
• Percentage of adult participants with fetal demise/stillbirth [Time frame: Through 6 weeks postpartum]
• Percentage of infant participants born small for gestational age [Time frame: Birth]
• Percentage of infant participants with low birth weight [Time frame: Birth]

Eligibility criteria

Inclusion criteria

• Willing and able to provide written informed consent for study participation for self and infant
• At screening, age 18 years or older
• Has a viable, intrauterine, singleton pregnancy with fetal ultrasound with an estimated gestational age (EGA) between 10 0/7 and 23 6/7 weeks (inclusive) at entry
• At entry, intending to deliver at a study-associated medical facility and remain in the geographic area of the study for the duration of anticipated follow-up
• Was diagnosed with HIV prior to the current pregnancy
• Has a documented plasma HIV RNA result less than 50 copies/mL from a specimen collected within 28 days prior to entry
• Has the following laboratory test results from a specimen collected within 28 days prior to entry (1) Grade 2 or lower platelets (greater than or equal to 50,000 cells/mm3 or greater than or equal to 50.00 x 109 cells/L); (2) Grade 1 or lower ALT (less than 2.5 x upper limit of normal; (3) Grade 1 or lower aspartate aminotransferase (AST)
• Received first dose of CAB LA + RPV LA prior to entry (before or after conception of the current pregnancy) and is expected to receive CAB LA + RPV LA on a Q4W schedule for the duration of study participation

Exclusion criteria

• History of treatment/virologic failure associated with documented or suspected viral resistance to CAB or RPV (including oral RPV)
• Has any of the following (1) HIV Subtype A6; (2) History of hypersensitivity reaction (HSR), known or suspected allergy to drugs under study, or any other contraindication to CAB or RPV; (3) Current contraindication to IM injection such as a current inflammatory skin condition that compromises the safety of IM injections or a dermatological condition which may interfere with the interpretation of ISRs; (4) Current use or anticipated need of therapeutic anticoagulation; (5) History of known or suspected bleeding disorder; (6) Current severe hepatic impairment (Class C) as determined by Child-Pugh classification; (7) History of suicidal ideation or attempt within six months of entry; (8) History of unstable or poorly controlled seizure disorder; (9) Current tuberculosis infection; (10) Current cervical intraepithelial neoplasia (CIN) 2 or 3, or malignancy other than Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma
• Has any of the following during the current pregnancy: (1) Abnormal placentation, including placenta previa (complete) and placenta accreta/increta/percreta; (2) Cervical cerclage/cervical incompetence; (3) Abnormal fetal anatomy
• Had any of the following in a previous pregnancy: (1) Eclampsia/Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome; (2) Intrauterine fetal demise (EGA greater than 20 weeks) without known nonrecurrent etiology; (3) Spontaneous very preterm delivery (less than 32 weeks); (4) Very LBW (less than 1500 g); (5) Cervical or abdominal cerclage due to cervical incompetence
• Receipt of any prohibited medication within seven days prior to entry
• Enrolled in another clinical trial of an investigational agent, device, or vaccine that may impact the PK of CAB or RPV
• Receipt of an investigational agent or chemotherapy within 30 days prior to study entry
• Adult-participant or fetus has any condition, such as uncontrolled diabetes, hypertension, or other comorbidities, that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

United States · 10 centers

• Site 4601, University of California, UC San Diego CRS — La Jolla
• Site 5048, University of Southern California — Los Angeles
• Site 5052, University of Colorado — Aurora
• Site 5030, Emory University School of Medicine — Atlanta
• Site 4001, Lurie Children's Hospital of Chicago CRS — Chicago
• Site 5092, Johns Hopkins University — Baltimore
• Site 5013, Jacobi Medical Center Bronx — The Bronx
• Site 6201, University of Pennsylvania — Philadelphia
• … and 2 more centers

Identifiers

NCT: NCT07637942 · IMPAACT 2050 · UM1AI068632 · UM1AI068616 · UM1AI106716

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗