Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy (CREATE)
Phase IV Study of the Pharmacokinetics of Long-Acting Injectable Cabotegravir and Rilpivirine in Pregnant and Postpartum Women With HIV in the United States
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.
Studie Overzicht
Toestand
Conditie
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 4
Contacten en locaties
Studiecontact
- Naam: Lisa Levy
- Telefoonnummer: 2028848480
- E-mail: LLEVY@FHI360.ORG
Studie Locaties
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California
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La Jolla, California, Verenigde Staten, 92093
- Nog niet aan het werven
- Site 4601, University of California, UC San Diego CRS
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Contact:
- Stephen Spector, MD
- Telefoonnummer: 858-534-7055
- E-mail: saspector@ucsd.edu
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Los Angeles, California, Verenigde Staten, 90033
- Nog niet aan het werven
- Site 5048, University of Southern California
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Contact:
- Alice Stek, MD
- Telefoonnummer: 323-226-3353
- E-mail: stek@usc.edu
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Colorado
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Aurora, Colorado, Verenigde Staten, 80045
- Werving
- Site 5052, University of Colorado
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Contact:
- Lisa Abuogi, MD
- Telefoonnummer: 303-358-5061
- E-mail: Lisa.Abuogi@childrenscolorado.org
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Nog niet aan het werven
- Site 5030, Emory University School of Medicine
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Contact:
- Martina Badell, MD
- Telefoonnummer: 404-778-3401
- E-mail: mbadell@emory.edu
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Illinois
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Chicago, Illinois, Verenigde Staten, 60614
- Werving
- Site 4001, Lurie Children's Hospital of Chicago CRS
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Contact:
- Jennifer Jao, MD, MPH
- Telefoonnummer: 312-227-4080
- E-mail: jjao@luriechildrens.org
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21287
- Nog niet aan het werven
- Site 5092, Johns Hopkins University
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Contact:
- Allison Agwu, MD
- Telefoonnummer: 410-614-3917
- E-mail: ageorg10@jhmi.edu
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New York
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The Bronx, New York, Verenigde Staten, 10461
- Nog niet aan het werven
- Site 5013, Jacobi Medical Center Bronx
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Contact:
- Andrew Wiznia, MD
- Telefoonnummer: 718-918-4664
- E-mail: andrew.wiznia@einsteinmed.edu
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104
- Werving
- Site 6201, University of Pennsylvania
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Contact:
- William Short, MD
- Telefoonnummer: 267-971-3275
- E-mail: william.short@pennmedicine.upenn.edu
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Tennessee
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Memphis, Tennessee, Verenigde Staten, 38105
- Nog niet aan het werven
- Site 6501, St Jude Children's Research Hospital
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Contact:
- Katherine Knapp, MD
- Telefoonnummer: 901-595-4645
- E-mail: katherine.knapp@stjude.org
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Texas
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Houston, Texas, Verenigde Staten, 77030
- Werving
- Site 5128, Baylor College of Medicine/Texas Children's Hospital
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Contact:
- Mary Paul, MD
- Telefoonnummer: 832-822-1038
- E-mail: mpaul@bcm.edu
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: CAB LA + RPV LA Initiation Pre Conception
Pregnant women with controlled HIV who were using CAB LA + RPV LA pre-conception, and continue to receive Q4W CAB LA + RPV LA |
Long-acting injectable cabotegravir and rilpivirine, initiated pre-conception. Participants will receive these drugs as prescribed outside the study by their non-study clinical care provider. Long-acting injectable cabotegravir and rilpivirine, initiated post-conception. Participants will receive these drugs as prescribed outside the study by their non-study clinical care provider. |
|
Experimenteel: CAB LA + RPV LA Initiation Post Conception
Pregnant women with controlled HIV who switch from oral SOC and initiate Q4W CAB LA + RPV LA post-conception, and continue to receive CAB LA + RPV LA |
Long-acting injectable cabotegravir and rilpivirine, initiated pre-conception. Participants will receive these drugs as prescribed outside the study by their non-study clinical care provider. Long-acting injectable cabotegravir and rilpivirine, initiated post-conception. Participants will receive these drugs as prescribed outside the study by their non-study clinical care provider. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model
Tijdsspanne: Measured from study entry through six weeks postpartum
|
Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model |
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
Tijdsspanne: 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 |
Measured from study entry through six weeks postpartum
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery
Tijdsspanne: Delivery
|
Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery |
Delivery
|
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Percentage of adult participants with virologic escape
Tijdsspanne: Measured from study entry through six weeks postpartum
|
Percentage of adult participants with virologic escape, defined as a single measurement of HIV RNA greater than or equal to 200 copies/mL |
Measured from study entry through six weeks postpartum
|
|
Percentage of adult participants with confirmed virologic failure
Tijdsspanne: Through 6 weeks postpartum
|
Percentage of adult participants with confirmed virologic failure, defined as two successive HIV RNA test results greater than or equal to 200 copies/mL from separate specimens collected at least two weeks apart |
Through 6 weeks postpartum
|
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Number of adult participants with HIV resistance to CAB or RPV who had confirmed virologic failure
Tijdsspanne: Through 6 weeks postpartum
|
Number of adult participants with HIV resistance to CAB or RPV using IAS-USA, in participants who experienced confirmed virologic failure |
Through 6 weeks postpartum
|
|
Number of infant participants with perinatal transmission
Tijdsspanne: Birth and six weeks post-birth
|
Number of infant participants with perinatal transmission |
Birth and six weeks post-birth
|
|
Percentage of adult participants with at least one Grade 3 or higher adverse event
Tijdsspanne: Measured from study entry through six weeks postpartum
|
Percentage of adult participants with at least one Grade 3 or higher adverse event |
Measured from study entry through six weeks postpartum
|
|
Percentage of adult participants with at least one serious adverse event
Tijdsspanne: Measured from study entry through six weeks postpartum
|
Percentage of adult participants with at least one serious adverse event |
Measured from study entry through six weeks postpartum
|
|
Percentage of infant participants with at least one serious adverse event
Tijdsspanne: Measured from birth through six weeks post-birth
|
Percentage of infant participants with at least one serious adverse event |
Measured from birth through six weeks post-birth
|
|
Percentage of adult participants with spontaneous abortion
Tijdsspanne: Through 6 weeks postpartum
|
Percentage of adult participants with spontaneous abortion less than 20 weeks gestation |
Through 6 weeks postpartum
|
|
Percentage of adult participants with fetal demise/stillbirth
Tijdsspanne: Through 6 weeks postpartum
|
Percentage of adult participants with fetal demise/stillbirth, at greater than or equal to 20 weeks gestation |
Through 6 weeks postpartum
|
|
Percentage of infant participants born small for gestational age
Tijdsspanne: Birth
|
Percentage of infant participants born small for gestational age, where birthweight is less than 10th percentile for sex and gestational age assigned at birth, based on Intergrowth 21st Standards |
Birth
|
|
Percentage of infant participants with low birth weight
Tijdsspanne: Birth
|
Percentage of infant participants with low birth weight, defined as less than 2500 grams |
Birth
|
|
Percentage of infant participants born preterm
Tijdsspanne: Birth
|
Percentage of infant participants born preterm, defined as less than 37 weeks gestation |
Birth
|
|
Percentage of mother-infant pairs with occurrence of any adverse pregnancy outcome
Tijdsspanne: Through 6 weeks postpartum
|
Percentage of mother-infant pairs with occurrence of any adverse pregnancy outcome. Outcomes include: spontaneous abortion (<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (<37 gestational weeks), small for gestational age (<10th percentile per INTERGROWTH 21st Standards), or neonatal death |
Through 6 weeks postpartum
|
|
Percentage of infant participants with a congenital anomaly
Tijdsspanne: Birth
|
Percentage of infant participants with a congenital anomaly based on the Metropolitan Atlanta Congenital Defects Program (MACDP) definition of defect |
Birth
|
|
Percentage of infant deaths
Tijdsspanne: Measured from birth through six weeks post-birth
|
Percentage of infant deaths |
Measured from birth through six weeks post-birth
|
|
Percentage of adult participants who would recommend CAB LA and RPV LA injections for other people living with HIV during pregnancy
Tijdsspanne: Six weeks postpartum
|
Percentage of adult participants who would recommend CAB LA and RPV LA injections |
Six weeks postpartum
|
Medewerkers en onderzoekers
Medewerkers
Onderzoekers
- Studie stoel: Rachel Scott, MD, MPH, MedStar Washington Hospital Center & MedStar Health Research Institute
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- IMPAACT 2050
- UM1AI068632 (Subsidie/contract van de Amerikaanse NIH)
- UM1AI068616 (Subsidie/contract van de Amerikaanse NIH)
- UM1AI106716 (Subsidie/contract van de Amerikaanse NIH)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Individual participant data that underlie results in the publication, after deidentification.
IPD-tijdsbestek voor delen
Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
IPD-toegangscriteria voor delen
- With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.
- For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.
- By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
IPD delen Ondersteunend informatietype
- LEERPROTOCOOL
- SAP
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