HIV-1-infectionPhase 1/2NCT05660980
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
A Phase 1/2 study testing Once daily CAB tablet + RPV tablet and Long acting CAB injectable + long acting RPV injectable in people with HIV-1-infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in 5 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 2 to 11 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Once daily CAB tablet + RPV tablet and Long acting CAB injectable + long acting RPV injectable
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 24 Jan 2024to 31 Mar 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Parents/caregivers of participants will be considered for enrollment to complete quantitative behavioral surveys and/or qualitative in-depth interviews (IDIs), as indicated in the SoE. One parent/caregiver per participant should be enrolled to complete all behavioral assessments, including the IDI, when applicable. Informed consent for parent/caregiver enrollment should be obtained at the entry visit, after the child participant's eligibility has been confirmed, and may be completed at a later date, if necessary. However, parent/caregiver consent must occur prior to any study assessments being conducted. The enrolled caregiver may be the different than the parent or legal guardian who provided written permission for the child to participate. If, at any point the enrolled parent/caregiver for a given participant withdraws from the study or is unable to complete remaining study assessments for any reason, they may be replaced.
- Caregivers must meet the following criteria to be eligible to enroll in IMPAACT 2036:
- 18 years of age or older
- Able and willing to provide written informed consent consistent with site IRB/EC policies and procedures
- Caregiver, defined as a biological parent, legal guardian, or other person who provides significant emotional, psychological, and/or physical care to a child enrolled in IMPAACT 2036, based on self-report
- Exclusion Criteria, Step 1: Entry for Cohort 1, Cohort 2a, and Cohort 2b
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- Potential participants must be excluded from the study if any of the conditions specified below are identified during the screening period (i.e., within 28 days prior to study entry). The screening period begins when parental permission and informed assent (if applicable) are obtained and ends immediately prior to enrollment. For criteria involving a potential participant's medical history, it is expected that each exclusionary condition will be assessed at screening and subsequently reviewed and confirmed on the day of study entry, prior to enrollment. In these criteria, "at entry" is used to refer to the day of enrollment in the study
- 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.
- Note: Prior receipt of NNRTIs for prophylaxis or treatment is not exclusionary
- 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.
- At entry, known active tuberculosis infection, as determined by the IoR or designee based on participant/parent/guardian report and available medical records.
- At entry, any ongoing pancreatitis as determined by the IoR or designee based on participant/parent/guardian report and available medical records.
- At entry, has symptoms suggestive of active coronavirus disease 2019 (COVID-19) or test results or contacts that require quarantine per local clinical practice, public health, and/or infection control guidelines as determined by the IoR or designee based on participant/parent/guardian report and available medical records.
- Note: Potential participants with symptoms suggestive of active COVID-19, test results, and/or contacts that require quarantine may resume screening (or be re-screened) after symptoms have resolved and applicable quarantine requirements have been completed.
- Receipt of any prohibited medication within 7 days prior to entry, with the exception of antiviral agents that are part of the participant's ART regimen, as determined by the site investigator based on participant/parent/guardian report and available medical records
- Note: Medications and vaccines approved for emergency use (e.g., COVID vaccines) that do not appear in the IMPAACT 2036 Prohibited and Precautionary Medications listing are not exclusionary may be administered as per standard of care.
- Any past or current exposure to CAB LA or RPV LA
- At entry, based on physical examination, has a current inflammatory skin condition that compromises the safety of intramuscular injections, as determined by the IoR or designee.
- At entry, based on physical examination, has a dermatological condition overlying the buttock or upper thigh region, which, in the IoR or designee's opinion, may interfere with the interpretation of injection site reactions.
- Enrolled in another clinical trial of an investigational agent, device, or vaccine.
- Has any documented or suspected clinically significant medical or psychiatric condition or any other condition or social circumstance that, in the opinion of the site investigator, would make participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
- Exclusion Criteria, Step 2: Continuation for Cohort 1 and Cohort 2a to injection phase
- Participants in Cohort 1 or Cohort 2a who meet any of the following criteria will be excluded from Step 2:
- Has permanently discontinued oral study product.
- Occurrence of any grade 3 or higher adverse event assessed as related to study product during Step 1.
- Any other condition or social circumstance situation that, in the opinion of the IoR or designee, would make continued study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Who cannot join
- Any condition or social circumstance situation that, in the opinion of the IoR or designee, would make study participation unsafe for the caregiver or the child study participant, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Trial locations and contacts
12 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
IMPAACT Clinicaltrials.gov Coordinator contact
12 sites in 5 countries
South Africa3 sites, 3 recruiting
- Recruiting
CRS 8052, Soweto IMPAACT
Johannesburg, 1864
Avy Violari, MD, 27-11-9899707, violari@mweb.co.za
- Recruiting
Site 8051, Wits RHI Shandukani Research Centre CRS
Johannesburg, 2001
Lee Fairlie, MD, 27-11-3585317, LFairlie@wrhi.ac.za
- Recruiting
Site 30300 Umlazi CRS Site
Umlazi, KwaZulu-Natal, 4066
Zulaykha Sarally-Moideen, MD, 27-31-6550811, sarally-moideen@caprisa.org
Thailand3 sites, 3 recruiting
- Recruiting
Siriraj Hospital, Mahidol University NICHD CRS (Site #5115)
Bangkok, Bangkoknoi, 10700
Kulkanya Chokephaibulkit, MD, 66-2-866-0225 ext. 5695, Kulkanya.cho@mahidol.ac.th
- Recruiting
CRS 31784, Chiang Mai University HIV Treatment CRS
Chiang Mai, 50202
Linda Aurpibul, MD, MPH, 66-53-936148 ext. 445, lindaa@rihes.org
- Recruiting
Site 5116, Chiangrai Prachanukroh Hospital NICHD CRS
Chiang Rai, 57000
Pradthana Ounchanum, MD, 66-8-5617-3329, doctorbaiplu@gmail.com
United States2 sites, 2 recruiting
- Recruiting
Site 5030, Emory University School of Medicine NICHD CRS
Atlanta, Georgia, 30322
Andrés Camacho-Gonzalez, MD, 404-727-5642, acamac2@emory.edu
- Recruiting
Site 6501, St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105
Aditya Gaur, 901-595-2862, aditya.gaur@stjude.org
Botswana2 sites, 2 recruiting
- Recruiting
Site 12701, Gaborone CRS
Gaborone
Gaerolwe Masheto, MD, 2673902671, gmasheto@bhp.org.bw
- Recruiting
Site 12702, Molepolole CRS
Gaborone
Gaerolwe Masheto, MD, 2673902671, gmasheto@bhp.org.bw
Brazil2 sites, 2 recruiting
- Recruiting
Site 5073, SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, 30130-100
Jorge Pinto, 55-31-34099822
- Recruiting
CRS 5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site
Rio de Janeiro, 21941-590
Ricardo Oliveira, MD, 55-21-941912, rh_oliveira@yahoo.com
About this study
Official title: Phase I/II Study of the Safety, Tolerability, Acceptability, and Pharmacokinetics 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
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
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- Once daily CAB tablet + RPV tablet, Long acting CAB injectable + long acting RPV injectable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Once daily CAB tablet + RPV tabletDrug
Tablet
Long acting CAB injectable + long acting RPV injectableDrug
Injectable
Long acting CAB injectable + long acting RPV injectableDrug
Injectable
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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. Receives: 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. Receives: Drug: Long acting CAB injectable + long acting RPV injectable |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC (Cohort 1, tablets)
Area under the curve from start of dose to 8 hours post dose
Measured: At week 2
CL/F (Cohort 1, tablets)
apparent clearance from start of dose to 8 hours post dose
Measured: At week 2
Cmax (Cohort 1, tablets)
Peak concentration from start of dose to 8 hours post dose
Measured: At week 2
Tmax (Cohort 1, tablets)
Time of maximal concentration from start of dose to 8 hours post dose
Measured: At week 2
Pre-dose concentrations (C0) (Cohort 1, tablets)
Measured: At week 2
Week 5 concentrations (C5WK) (Cohort 1, injections)
Measured: Through week5
Week 12 concentrations (C12WK) (Cohort 1, injections)
Measured: Through week 12
Trough concentrations (Ct) prior to IM doses through Week 24 (Cohort 1, injections)
Measured: Through week 24
Accumulation Ratio at week 24 and week 8 (Cohort 1, injections)
Measured: 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)
Measured: 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)
Measured: Through week 4a
Proportion of children who experience an SAE during the CAB + RPV oral lead-in period (Cohort 1)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Week 4b through week 28
Proportion of children who experience an SAE during the 24 weeks of CAB + RPV (oral and injectable) (Cohort 1)
Measured: 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)
Measured: 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
Measured: At week 8, 48 and 72
Ct prior to IM doses through Week. 24 and Week. 48 (Cohort 2a)
Measured: At Week. 24 and Week. 48
Ct prior to IM doses through Wk. 20 and Wk. 44 (Cohort 2b)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Through week 72
Median for CD4 count and percentage at Weeks 24, 48 and 72 (Cohort 1)
Measured: At weeks 24, 48 and 72
Median change from baseline CD4 count and percentage at Weeks 24, 48 and 72 (Cohort 1)
Measured: At weeks 24, 48 and 72
Child and/or parent/caregiver response to questionnaires (Cohort 2)
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)
Measured: at week 44 and 48
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: At week 8 and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2022
- Study start24 Jan 2024
- Primary completion22 Oct 2026 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05660980
- Sponsor's protocol ID
- IMPAACT 2036
- Other IDs
- DAIDS Study ID
- Status last verified
- May 2026
- First submitted
- 13 Dec 2022
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.