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
- Conditions
- HIV-1-infection
- Interventions
- Drug: Long acting CAB injectable + long acting RPV injectableDrug: Once daily CAB tablet + RPV tablet
- Registration Number
- NCT05660980
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
Not provided
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 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 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 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
CRS 31784, Chiang Mai University HIV Treatment CRS
🇹🇭Chiang Mai, Thailand
Site 5116, PHPT-Chiangrai Prachanukroh Hospital NICHD CRS
🇹🇭Chiang Rai, Thailand