CREATE - Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy

NCT06336434 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: IMPAACT 2040
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 8

Brief Summary

This is a Phase I/II, multicenter, open-label, non-randomized study with four groups to characterize the pharmacokinetics and safety of Cabotegravir (CAB) and Rilpivirine (RPV) long-acting injectable (LA) during pregnancy and postpartum among people with HIV-1 viral suppression and their infants.

Conditions

HIV-1-infection; Pregnancy; Postpartum

Keywords

Pregnancy; Long-acting; cabotegravir; rilpivirine; pharmocokinetics; chestfeeding; breastfeeding

Outcome Measures

Primary Outcomes (3)

• PK trough of CAB LA measured in plasma in pregnancy and postpartum

  Through 18 weeks post-partum

• Percentage of adults with at least one Grade 3 or higher adverse event in pregnancy and through 18 weeks postpartum

  Through 18 weeks post-partum

• Percentage of adults with at least one serious adverse event in pregnancy and through 18 weeks postpartum

  Through 18 weeks post-partum

Secondary Outcomes (22)

• PK trough measured in plasma in pregnancy and postpartum

  Through 18 weeks postpartum

• Percentage of adults with HIV-1 RNA less than 50 copies/mL at delivery

  Through Delivery

• Percentage of adults with HIV-1 RNA less than 50 copies/mL at delivery using the standardized FDA snapshot algorithm

  Through Delivery

• Percentage of adults with virologic escape (single measurement of greater than or equal to 200 copies/mL) from study entry through pregnancy and through 18 weeks postpartum

  Through 18 weeks postpartum

• Percentage of adults with confirmed virologic failure through 18 weeks postpartum

  Through 18 weeks postpartum

Study Arms (4)

Q4W Switch

EXPERIMENTAL

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression on oral antiretroviral therapy willing to switch to an every four week (Q4W) CAB LA + RPV LA regimen.

Drug: CAB LA 600mg; Drug: RPV LA 900mg; Drug: CAB LA 400mg; Drug: RPV LA 600mg

Q8W Switch

EXPERIMENTAL

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression on oral antiretroviral therapy willing to switch to an every eight week (Q8W) CAB LA + RPV LA regimen.

Drug: CAB LA 600mg; Drug: RPV LA 900mg

Q4W Continuation

EXPERIMENTAL

Pregnant people 19 4/7 weeks gestation or less with HIV-1 viral suppression who were using every 4 week CAB LA + RPV LA at and since conception and are willing to continue their current CAB LA + RPV LA regimen.

Drug: CAB LA 400mg; Drug: RPV LA 600mg

Q8W Continuation

EXPERIMENTAL

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression who were using every 8 week CAB LA + RPV LA at and since conception and are willing to continue their current CAB LA + RPV LA regimen.

Drug: CAB LA 600mg; Drug: RPV LA 900mg

Interventions

CAB LA 600mg DRUG

600mg (3mL) IM Injection

Q4W Switch; Q8W Continuation; Q8W Switch

RPV LA 900mg DRUG

900mg (3mL) IM Injection

Q4W Switch; Q8W Continuation; Q8W Switch

CAB LA 400mg DRUG

400mg (2mL) IM Injection

Q4W Continuation; Q4W Switch

RPV LA 600mg DRUG

600mg (2mL) IM injection

Q4W Continuation; Q4W Switch

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent for study participation for self and infant.
• Note: All sites must follow all applicable IRB/EC policies and procedures; for US sites, this includes single IRB (sIRB) policies and procedures.
• At screening, age 18 years or older.
• At entry, evidence of a viable, intrauterine, singleton pregnancy with fetal ultrasound performed per protocol and within the following estimated gestational age (EGA) ranges per protocol:
• Switch Group: EGA between 10 0/7 and 19 4/7 weeks (inclusive) at entry.
• Continuation Group: EGA less than or equal to 19 4/7 weeks at entry.
• Note: If adequate ultrasound results are not available from medical records at screening per protocol, an ultrasound must be performed prior to study entry.
• At entry, intending to deliver at a study-associated medical facility, remain in the geographic area of the study for the duration of anticipated follow-up, and attend regularly scheduled study visits.
• Confirmed HIV-1 infection based on documented testing of two samples collected from two separate blood collection tubes per Sample #1 and Sample #2 requirements. Test results may be obtained from medical records or from testing performed at screening (i.e., from specimens collected within 28 days prior to entry):
• For results obtained from medical records, adequate source documentation, including the date of specimen collection, date of testing or date of test result, name of test/assay performed, and test result, must be available in study records prior to study entry. Requirements related to laboratory operations (e.g., Good Clinical Laboratory Practice \[GCLP\], Clinical Laboratory Improvement Amendments \[CLIA\], Virology Quality Assurance \[VQA\]) and related to regulatory authority approvals (e.g., FDA) do not apply to results obtained from medical records.
• If adequate source documentation is not available, Sample #1 and/or Sample #2 should be collected during the study screening period and tested in the site's designated testing laboratory.
• If both samples are tested using antibody tests, at least one of the samples must be tested in a laboratory that operates according to CLIA or equivalent (for US sites) or GCLP (for South African sites) guidelines and participates in an appropriate external quality assurance program. If nucleic acid testing (NAT) is used, at least one test must be performed in the site's CLIA-certified or equivalent (for US sites) or VQA-certified (for South African sites) laboratory.
• Sample #1 may be tested using any of the following:
• Two rapid antibody-based tests from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used)
• One enzyme immunoassay (EIA) or Western blot (WB) or immunofluorescence assay or chemiluminescence assay

You may not qualify if:

• Within nine months (270 days) prior to entry, any plasma HIV-1 RNA measurement greater than or equal to 200 copies/mL or two or more detectable plasma HIV-1 RNA measurements greater than or equal to 50 copies/mL at least 14 days apart.
• History of treatment/virologic failure associated with documented or presumed viral resistance to NNRTI or INSTI, defined as two consecutive plasma HIV-1 RNA measurements greater than or equal to 200 copies/mL after initial suppression to less than 50 copies/mL.
• Has any of the following, as determined by the site investigator based on participant report, clinical evidence, and/or available antenatal/medical care records:
• Historical or suspected resistance to NNRTI and INSTI classes, (i.e., presence of NNRTI and/or INSTI resistance associated substitutions or a phenotype resistance result to any NNRTI and/ or INSTI).
• Note: If there are questions regarding suspected resistance, the site investigator should consult with the CMC prior to enrolling the participant.
• HIV-1 Subtype A6
• Hypersensitivity reaction (HSR), known or suspected allergy to study product components, or any other contraindication to CAB or RPV.
• 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 (including but not limited to gluteal implants).
• Known ARV treatment interruption (greater than 30 consecutive days) in the 24 months prior to entry.
• For participants on EFV, known treatment interruption (greater than seven consecutive days) in the 24 months prior to entry.
• Any use of Nevirapine (ever), including, but not limited to a short course regimen to prevent perinatal transmission.
• At entry, current use or anticipated need of therapeutic anticoagulation (e.g., low molecular weight heparin, coumadin, heparin, or enoxaparin).
• History of known or suspected bleeding disorder.
• Current severe hepatic impairment (Class C) as determined by Child-Pugh classification.
• Suicidal ideation or attempt within six months of entry, based on completion of the Columbia-Suicide Severity Rating Scale (C-SSRS).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (8)

Site 4601, University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program

La Jolla, California, 92093-0672, United States

Location

Site 5048, University of Southern California LA

Los Angeles, California, 90033, United States

Location

Site 5092, Johns Hopkins University, Baltimore

Baltimore, Maryland, 21287, United States

Location

Site 5013, Jacobi Medical Center Bronx

The Bronx, New York, 10461, United States

Location

Site 8051 - Wits RHI Shandukani Research Centre

Johannesburg, 2001, South Africa

Location

Site 8052, Soweto

Johannesburg, South Africa

Location

Site 8950, FAMCRU CRS

Parow, 7505, South Africa

Location

Site 30300, Umlazi Clinical Research Site

Umlazi, 4066, South Africa

Location

MeSH Terms

Conditions

Breast Feeding

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 28, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2028
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: 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/ resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

US (4); ZA (4)