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

Phase 1

Recruiting

• Conditions: HIV-1-infection
• Interventions: Drug: Long acting CAB injectable + long acting RPV injectable; Drug: Once daily CAB tablet + RPV tablet

• Registration Number: NCT05660980
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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

Detailed Description

This is a Phase I/II, multicenter, open-label, non-comparative study to evaluate the safety, tolerability, acceptability, and PK of oral CAB and oral RPV followed by long-acting injectable CAB (CAB LA) and long-acting injectable RPV (RPV LA) to propose the weight-band dosing in virologically suppressed children living with HIV-1 aged two to less than 12 years. The study will also assess the long-acting injectable regimen with and without an oral lead-in period in the same study population.

Following completion of the study, if it is not possible for participants to access injections of CAB LA and RPV LA from non-study sources all participants may enter a Study Safety Extension (SSE) period. During the SSE period ongoing safety information to monitor for toxicities will be collected.

Study Timeline

• Study First Submitted: 2022-12-13
• Study First Submitted QC: 2022-12-13
• Study First Posted: 2022-12-21
• Study Start: 2024-01-24
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-23
• Last Update Posted: 2025-05-29
• Primary Completion: 2026-06-15
• Study Completion: 2027-07-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2B	Long acting CAB injectable + long acting RPV injectable	Cohort 2B: Q4W or Q8W intramuscular injection doses of CAB LA + RPV LA.
Cohort 1	Long acting CAB injectable + long acting RPV injectable	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)
Cohort 2A	Once daily CAB tablet + RPV tablet	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.
Cohort 1	Once daily CAB tablet + RPV tablet	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)
Cohort 2A	Long acting CAB injectable + long acting RPV injectable	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.

Primary Outcome Measures

Name	Time	Method
AUC (Cohort 1, tablets)	At week 2	Area under the curve from start of dose to 8 hours post dose
CL/F (Cohort 1, tablets)	At week 2	apparent clearance from start of dose to 8 hours post dose
Cmax (Cohort 1, tablets)	At week 2	Peak concentration from start of dose to 8 hours post dose
Week 5 concentrations (C5WK) (Cohort 1, injections)	Through week5
Week 12 concentrations (C12WK) (Cohort 1, injections)	Through week 12
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 a drug-related safety failure event during the 24 weeks of CAB + RPV (oral and injectable) (Cohort 1)	Week 4b through week 28
Tmax (Cohort 1, tablets)	At week 2	Time of maximal concentration from start of dose to 8 hours post dose
Pre-dose concentrations (C0) (Cohort 1, tablets)	At week 2
Accumulation Ratio at week 24 and week 8 (Cohort 1, injections)	At week 8 and 24
Trough concentrations (Ct) prior to IM doses through Week 24 (Cohort 1, injections)	Through week 24
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 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
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

Secondary Outcome Measures

Name	Time	Method
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
Proportion of children who experience an SAE through Weeks 48 and 72 of CAB + RPV (oral and injectable) (Cohort 1)	Through week 48 and 72
Proportion of children who experience premature permanent discontinuation study treatment due to an adverse event through Weeks 48 and 72 of CAB + RPV (oral and injectable) (Cohort 1)	Through week 48 and 72
Proportion of children who have HIV-1 RNA <50 and ≥50, copies/ml at Weeks 24, 48, and 72 using the FDA Snapshot algorithm (Cohort 1)	At weeks 24, 48 and 72
Proportion of children who have HIV-1 RNA <200 and ≥200 copies/ml at Weeks 24, 48, and 72 using the FDA Snapshot algorithm (Cohort 1)	At weeks 24, 48 and 72
Proportion of children with confirmed virologic failure at Weeks 24, 48 and 72 while on CAB + RPV (Cohort 1)	At weeks 24, 48 and 72
Child and/or parent/caregiver responses to questionnaires about CAB or RPV side effects, pain associated with injections, and injection site reactions at Weeks 24, 48, and 72 (Cohort 1)	At Weeks 24, 48, and 72
Child and/or parent/caregiver reported attitudes about CAB or RPV, including willingness to use at Weeks 24, 48, and 72 (Cohort 1)	At weeks 24, 48 and 72
Proportion of participants who had genotypic and phenotypic resistance to CAB or RPV among children who experience virologic failure while on CAB + RPV (Cohort 1)	Through week 72
Median for CD4 count and percentage at Weeks 24, 48 and 72 (Cohort 1)	At weeks 24, 48 and 72
Median change from baseline CD4 count and percentage at Weeks 24, 48 and 72 (Cohort 1)	At weeks 24, 48 and 72
Child and/or parent/caregiver response to questionnaires (Cohort 2)	at week 44 and 48	about CAB or RPV side effects, pain associated with injections and injection site reactions for children who are on 48 weeks of CAB+RPV(oral and injectable) OR 44 weeks of CAB LA+RPV LA (injectable)
Child and/or parent/caregiver reported attitudes about CAB (Cohort 2) or RPV, including willingness to use for children who are on 48 weeks of CAB + RPV (oral and injectable) OR 44 weeks of CAB LA + RPV LA (injectable)	At week 44 and 48
Proportion of children who experience a drug-related safety failure event during the 48 weeks of CAB + RPV (oral and injectable) OR the 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Proportion of children who experience a grade 3 or higher adverse event during the 48 weeks of CAB + RPV (oral and injectable) OR the 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Proportion of children who experience an SAE during the 48 weeks of CAB + RPV (oral and injectable) OR the 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Proportion of children who experience premature permanent discontinuation study treatment due to an adverse event during the 48 weeks of CAB + RPV (oral and injectable) OR the 44 weeks of CAB LA + RPV (Cohort 2) LA (injectable)	At week 44 and 48
Proportion of children who have HIV-1 RNA <50 and ≥50, copies/ml using the FDA Snapshot algorithm for children who are on 48 weeks of CAB + RPV (oral and injectable) OR 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Proportion of children who have HIV-1 RNA <200 and ≥200 copies/ml using the FDA Snapshot algorithm for children who are on 48 weeks of CAB + RPV (oral and injectable) OR 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Proportion of children with confirmed virologic failure while on treatment for children who are on 48 weeks of CAB + RPV (oral and injectable) OR 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Median and Interquartile Range for CD4 count and percentage for children who are on 48 weeks of CAB + RPV (oral and injectable) OR 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Median and Interquartile Range change from baseline CD4 count and percentage for children who are on 48 weeks of CAB + RPV (oral and injectable) OR 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
Proportion of participants who had genotypic and phenotypic resistance to CAB and RPV among children who experience virologic failure while on 48 weeks of CAB + RPV (oral and injectable) OR while on 44 weeks of CAB LA + RPV LA (injectable) (Cohort 2)	At week 44 and 48
LA dosing: Ct prior to IM doses at Wk. 48 and Wk. 72 and accumulation ratios (Wk. 48:Wk. 8 and Wk. 72:Wk. 8) (Cohort 1)	At week 8 and 48

Trial Locations

Locations (12)

Site 5030, Emory University School of Medicine NICHD CRS; 🇺🇸 Atlanta, Georgia, United States

Site 6501, St. Jude Children's Research Hospital CRS; 🇺🇸 Memphis, Tennessee, United States

Site 12701, Gaborone CRS; 🇧🇼 Gaborone, Botswana

Site 12702, Molepolole CRS; 🇧🇼 Gaborone, Botswana

Site 5073, SOM Federal University Minas Gerais Brazil NICHD CRS; 🇧🇷 Belo Horizonte, Brazil

CRS 5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site; 🇧🇷 Rio De Janeiro, Brazil

Site 30300 Umlazi CRS Site; 🇿🇦 Umlazi, Kwa Zulu Natal, South Africa

Site 8051, Wits RHI Shandukani Research Centre CRS; 🇿🇦 Johannesburg, South Africa

CRS 8052, Soweto IMPAACT; 🇿🇦 Johannesburg, South Africa

Siriraj Hospital, Mahidol University NICHD CRS (Site #5115); 🇹🇭 Bangkok, Bangkoknoi, Thailand

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