Study of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living With HIV-1, Two to Less Than 12 Years of Age

NCT05660980 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IMPAACT 2036DAIDS Study ID
• Study Type: interventional
• Target: 90
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, tolerability, and acceptability of a long-acting injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living with HIV-1, Two to Less Than 12 Years of Age

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (17)

• AUC (Cohort 1, tablets)

  Area under the curve from start of dose to 8 hours post dose

  At week 2

• CL/F (Cohort 1, tablets)

  apparent clearance from start of dose to 8 hours post dose

  At week 2

• Cmax (Cohort 1, tablets)

  Peak concentration from start of dose to 8 hours post dose

  At week 2

• Tmax (Cohort 1, tablets)

  Time of maximal concentration from start of dose to 8 hours post dose

  At week 2

• Pre-dose concentrations (C0) (Cohort 1, tablets)

  At week 2

• Week 5 concentrations (C5WK) (Cohort 1, injections)

  Through week5

• Week 12 concentrations (C12WK) (Cohort 1, injections)

  Through week 12

• Trough concentrations (Ct) prior to IM doses through Week 24 (Cohort 1, injections)

  Through week 24

• Accumulation Ratio at week 24 and week 8 (Cohort 1, injections)

  At week 8 and 24

• Proportion of children who experience a drug related safety event during the CAB + RPV oral lead-in period (Cohort 1)

  Through week 4a

• Proportion of children who experience a grade 3 of higher adverse event during the CAB + RPV oral lead-in period (Cohort 1)

  Through week 4a

• Proportion of children who experience an SAE during the CAB + RPV oral lead-in period (Cohort 1)

  Through week 4a

• Proportion of children who experience premature permanent discontinuation study treatment due to an adverse event during the CAB + RPV oral lead-in period (Cohort 1)

  Through week 4a

• Proportion of children who experience a drug-related safety failure event during the 24 weeks of CAB + RPV (oral and injectable) (Cohort 1)

  Week 4b through week 28

• Proportion of children who experience a grade 3 or higher adverse event during the 24 weeks of CAB + RPV (oral and injectable) (Cohort 1)

  Week 4b through week 28

• Proportion of children who experience an SAE during the 24 weeks of CAB + RPV (oral and injectable) (Cohort 1)

  Week 4b through week 28

• Proportion of children who experience premature permanent discontinuation study treatment due to an adverse event during the 24 weeks of CAB + RPV (oral and injectable) (Cohort 1)

  Week 4b through week 28

Secondary Outcomes (28)

• Accumulation ratios Wk 24:Wk 8 and Wk 48: Wk 8 (Cohort 2a), Wk 20:Wk4 and Wk 44: Wk 4 (Cohort 2b

  At week 8, 48 and 72

• Ct prior to IM doses through Week. 24 and Week. 48 (Cohort 2a)

  At Week. 24 and Week. 48

• Ct prior to IM doses through Wk. 20 and Wk. 44 (Cohort 2b)

  At week 20 and 44

• Proportion of children who experience a drug-related safety failure event through Weeks 48 and 72 of CAB + RPV (oral and injectable) (Cohort 1)

  Through week 48 and 72

• Proportion of children who experience a grade 3 or higher adverse event through Weeks 48 and 72 of CAB + RPV (oral and injectable) (Cohort 1)

  Through week 48 and 72

Other Outcomes (5)

• CAB and RPV concentrations 8 to 48 weeks following final IM dose

  At week 8 and 48

• Proportion of children who experience a drug-related safety failure event through 48 weeks following permanent discontinuation of CAB LA + RPV LA

  Through week 48

• Proportion of children who experience a grade 3 or higher adverse event through 48 weeks following permanent discontinuation of CAB LA + RPV LA

  Through week 48

Study Arms (3)

Cohort 1

EXPERIMENTAL

Cohort 1 will receive Once daily oral CAB + oral RPV through the Week 4b visit, followed by intramuscular injection doses of CAB LA + RPV LA every four weeks (Q4W dosing regimen) or every eight weeks (Q8W dosing regimen)

Drug: Once daily CAB tablet + RPV tablet; Drug: Long acting CAB injectable + long acting RPV injectable

Cohort 2A

EXPERIMENTAL

Cohort 2A: Once daily doses of oral CAB + oral RPV through the Week 4b visit, followed by Q4W or Q8W intramuscular injection doses of CAB LA + RPV LA.

Drug: Once daily CAB tablet + RPV tablet; Drug: Long acting CAB injectable + long acting RPV injectable

Cohort 2B

EXPERIMENTAL

Cohort 2B: Q4W or Q8W intramuscular injection doses of CAB LA + RPV LA.

Drug: Long acting CAB injectable + long acting RPV injectable

Interventions

Once daily CAB tablet + RPV tablet DRUG

Tablet

Cohort 1; Cohort 2A

Long acting CAB injectable + long acting RPV injectable DRUG

Injectable

Cohort 1; Cohort 2A

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent or legal guardian is willing and able to provide written permission for child's study participation and, when applicable per institutional review board/ethics committee (IRB/EC) policies and procedures, child is willing and able to provide written assent for study participation.
• Note: All sites must follow all applicable IRB/EC policies and procedures; for US sites, this includes single IRB (sIRB) policies and procedures.
• Age two years old to less than 12 years old at entry
• Body weight ≥10 kgs and \<40 kgs at entry
• At entry, willing and able to comply with the study visit schedule and other study requirements, as determined by the site investigator or designee.
• 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 during the study screening period
• Has been on a stable unchanged ART regimen consisting of two or more drugs from two or more antiretroviral drug classes for at least six consecutive months (defined as 180 consecutive days) prior to entry.
• Has no prior history of switching ART regimens for reasons related to treatment failure based on parent/guardian report and/or available medical records.
• From a specimen collected less than six months (defined as within 179 days) prior to entry, has at least one of the following documented plasma HIV-1 RNA results:
• \<50 copies/mL, or
• less than the lower limit of detection of the assay
• From a specimen collected in the 6-18 months (defined as 180 to 545 days) prior to entry, has at least one of the following documented plasma HIV-1 RNA results:
• \<50 copies/mL, or
• less than the lower limit of detection of the assay
• At screening, a documented plasma HIV-1 RNA \<50 copies/mL.

You may not qualify if:

• Within 6 months prior to entry, any HIV-1 RNA value \>400 copies/mL OR two consecutive "viral blips," defined as an HIV-1 RNA value ≥50 copies/mL but ≤400 copies/mL.
• As determined by the IoR or designee, and based on available medical records, known or suspected resistance to NNRTIs.
• As determined by the IoR or designee, and based on available medical records, known or suspected resistance to INSTIs.
• Ongoing congestive heart failure, symptomatic arrhythmia, or any current clinically significant cardiac disease, as determined by the IoR or designee, and based on available medical records.
• Has any of the following, as determined by the IoR or designee based on participant/parent/guardian report and available medical records:
• Current hepatitis C infection
• Current clinically significant hepatic disease
• Current or anticipated need for chronic anti-coagulation
• History of known or suspected bleeding disorder, including a history of prolonged bleeding
• History of sensitivity to heparin or heparin-induced thrombocytopenia, as determined by the IoR or designee, based on available medical records
• Risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, hypomagnesemia)
• Known or suspected allergy to study product components.
• Known phobia to needles
• More than one seizure within one year (defined as within 365 days) prior to entry, or unstable or poorly controlled seizure disorder, as determined by the IoR or designee, and based on available medical records.
• Has the following combination of laboratory test results at screening (i.e., from specimens collected within 28 days prior to entry): ALT greater than or equal to 3 x ULN and total bilirubin greater than or equal to 1.5 x ULN and direct bilirubin greater than 35% of total bilirubin.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institute of Mental Health (NIMH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (12)

Site 5030, Emory University School of Medicine NICHD CRS

Atlanta, Georgia, 30322, United States

RECRUITING

Site 6501, St. Jude Children's Research Hospital CRS

Memphis, Tennessee, 38105, United States

RECRUITING

Site 12701, Gaborone CRS

Gaborone, Botswana

ACTIVE NOT RECRUITING

Site 12702, Molepolole CRS

Gaborone, Botswana

ACTIVE NOT RECRUITING

Site 5073, SOM Federal University Minas Gerais Brazil NICHD CRS

Belo Horizonte, 30130-100, Brazil

ACTIVE NOT RECRUITING

CRS 5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site

Rio de Janeiro, 21941-590, Brazil

ACTIVE NOT RECRUITING

Site 30300 Umlazi CRS Site

Umlazi, KwaZulu-Natal, 4066, South Africa

ACTIVE NOT RECRUITING

Site 8051, Wits RHI Shandukani Research Centre CRS

Johannesburg, 1863, South Africa

ACTIVE NOT RECRUITING

CRS 8052, Soweto IMPAACT

Johannesburg, 2091, South Africa

ACTIVE NOT RECRUITING

Siriraj Hospital, Mahidol University NICHD CRS (Site #5115)

Bangkok, Bangkoknoi, 10700, Thailand

ACTIVE NOT RECRUITING

CRS 31784, Chiang Mai University HIV Treatment CRS

Chiang Mai, 50202, Thailand

ACTIVE NOT RECRUITING

Site 5116, PHPT-Chiangrai Prachanukroh Hospital NICHD CRS

Chiang Rai, 57000, Thailand

ACTIVE NOT RECRUITING

Central Study Contacts

Rachel Scheckter

CONTACT

(919) 321-3540; rscheckter@fhi360.org

IMPAACT Clinicaltrials.gov Coordinator

CONTACT

impaact.ctgov@fstrf.org

Study Design

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

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: January 24, 2024
• Primary Completion (Estimated): September 10, 2026
• Study Completion (Estimated): August 15, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

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

ZA (3); TH (3); BR (2); US (2); BO (2)