Cabotegravir + Rilpivirine for HIV in Children

Recruiting at 14 trial locations

Overseen By IMPAACT Clinicaltrials.gov Coordinator

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Disqualifiers: Hepatitis C, Cardiac disease, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of two injectable medications, Cabotegravir and Rilpivirine, for children living with HIV. Researchers seek to understand how these long-acting treatments perform in children who have already maintained control of their HIV with other medications. The trial involves administering these medicines either daily by mouth or as injections every four or eight weeks. Children aged 2 to under 12 years, who have stable HIV treatment and no recent treatment failures, may be suitable candidates for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications. However, participants must have been on a stable antiretroviral therapy (ART) regimen for at least six months before joining the study, and any prohibited medications must not have been taken within 7 days prior to entry.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of cabotegravir and rilpivirine, administered as long-lasting injections, is generally well-tolerated. In a real-world study with patients using these treatments, only a small percentage experienced significant issues. Specifically, after one year, only 2% of patients had problems controlling their HIV, indicating the treatment's effectiveness and safety for most individuals.

Another study found that adults and teenagers receiving these injections every four to eight weeks maintained similar drug levels in their bodies. This consistency indicates that the treatment is stable and predictable, which bodes well for safety.

These drugs are already approved for adults, suggesting their safety. While this trial targets children aged two to under twelve, existing data provides a positive indication of how the treatment might work for this younger group. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Cabotegravir and Rilpivirine for treating HIV in children because they offer a new delivery method that could simplify treatment. Unlike standard HIV treatments that often require daily oral pills, this combination allows for long-acting intramuscular injections every four or eight weeks. This means fewer doses and potentially better adherence, making it easier for kids and their caregivers to manage the condition. Additionally, these drugs target the virus with a long-acting formulation, which is a significant advancement over many current therapies.

What evidence suggests that Cabotegravir and Rilpivirine might be an effective treatment for HIV in children?

Research shows that long-acting injectable cabotegravir and rilpivirine effectively control the HIV virus. For example, a study found that most participants maintained low virus levels over 24 months, with very few experiencing an increase. This trial will evaluate the treatment in children, with participants in different cohorts receiving various dosing regimens. In teenagers and young adults with HIV, these injections improve adherence to their treatment plan. Regular treatment is crucial for controlling the virus. Overall, this treatment appears promising for managing HIV effectively. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for HIV-positive children aged 2 to less than 12 years, weighing between 10 and <40 kgs, with a stable ART regimen for at least six months. They must have an undetectable viral load and no history of treatment failure or resistance to certain HIV drugs. Children with bleeding disorders, needle phobia, active tuberculosis, significant heart conditions or seizures are excluded.

Inclusion Criteria

I am between 2 and 11 years old.

Parent or legal guardian is willing and able to provide written permission for child's study participation

Willing and able to comply with the study visit schedule and other study requirements

Exclusion Criteria

HIV-1 RNA value >400 copies/mL within 6 months prior to entry or two consecutive 'viral blips'

My condition is resistant to certain HIV medications.

Living outside the US

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Oral Treatment

Participants receive once daily doses of oral CAB + oral RPV through the Week 4b visit

4 weeks

Weekly visits (in-person)

Long-acting Injectable Treatment

Participants receive Q4W or Q8W intramuscular injection doses of CAB LA + RPV LA

44-48 weeks

Every 4 or 8 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir and Rilpivirine

Trial Overview The study tests the safety and effectiveness of oral tablets versus long-acting injectables of two HIV medications: Cabotegravir (CAB) and Rilpivirine (RPV). It aims to understand how these treatments work in young children who already have controlled HIV.

How Is the Trial Designed?

Group I: Cohort 2B Experimental Treatment 1 Intervention

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

Group II: Cohort 2A Experimental Treatment 2 Interventions

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.

Group III: Cohort 1 Experimental Treatment 2 Interventions

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)

Cabotegravir and Rilpivirine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cabenuva for:

• HIV-1 infection in virologically suppressed adults

Approved in European Union as Vocabria and Rekambys for:

• HIV-1 infection in virologically suppressed adults

Approved in Canada as Cabenuva for:

• HIV-1 infection in virologically suppressed adults

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Cabotegravir (CAB) combined with rilpivirine (RPV) is the first long-acting dual therapy approved for HIV-1 treatment, showing comparable maintenance of viral suppression over 160 weeks with low rates of virological failure.

This regimen offers a convenient alternative to daily oral therapy, as it is administered via intramuscular injections every 4 weeks, with minimal adverse effects and no negative impact on renal or bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir-Rilpivirine: The First Complete Long-Acting Injectable Regimen for the Treatment of HIV-1 Infection. Durham, SH., Chahine, EB.[2022]

In a Phase 2b study involving 97 adults living with HIV-1, the long-acting formulation of cabotegravir and rilpivirine (CAB+RPV) administered every 2 months successfully maintained virologic suppression, with no participants showing HIV-1 RNA levels above 50 copies/ml after 12 months.

The long-acting CAB+RPV treatment had a favorable safety profile, with no new safety concerns identified, and 88% of participants preferred this regimen over their previous daily oral treatment, indicating high treatment satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. Mills, A., Richmond, GJ., Newman, C., et al.[2023]

In a study of treatment-naive and experienced patients in South Africa, 10% of treatment-naive patients and 74.5% of those failing treatment had rilpivirine drug resistance mutations (DRMs), indicating a high prevalence of resistance in those already on treatment.

The findings suggest that targeted genotyping for rilpivirine DRMs may be necessary before starting long-acting cabotegravir and rilpivirine (CAB/RPV LA), complicating the public health strategy for HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of rilpivirine cross-resistance on long-acting cabotegravir-rilpivirine in low and middle-income countries. Steegen, K., Chandiwana, N., Sokhela, S., et al.[2023]

Long-acting injectable therapies, cabotegravir (CAB) and rilpivirine (RPV), have been shown to be as effective as traditional oral antiretroviral therapy (ART) for HIV-1, maintaining efficacy over 96 weeks in clinical trials with virologically suppressed adults.

CAB has also demonstrated effectiveness as a preexposure prophylaxis (PrEP) option, significantly reducing HIV infections compared to daily oral medication, indicating its potential for broader use in HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Bares, SH., Scarsi, KK.[2023]

CABENUVA™, a combination of extended-release injectable cabotegravir and rilpivirine, has been approved in Canada for treating HIV-1 in adults who are already virologically stable and suppressed.

The approval is based on positive results from the ATLAS and FLAIR trials, indicating that this regimen can effectively replace current antiretroviral therapies for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir Plus Rilpivirine: First Approval. Markham, A.[2021]

Long-acting cabotegravir/rilpivirine (CAB/RPV) was effective in achieving undetectable HIV RNA levels in a patient with a history of virologic failure within just two months of treatment initiation.

The case also highlights the occurrence of immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium-intracellulare infection after starting CAB/RPV, indicating that while the treatment is effective, it can lead to complications in patients with underlying infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. Al-Handola, R., Chinnappan, J., Bakeer, M., et al.[2023]

Physiologically based pharmacokinetic (PBPK) modeling predicted that coadministering rifampicin with long-acting cabotegravir could reduce its effectiveness by 41%-46%, potentially leading to subtherapeutic levels.

Rilpivirine concentrations were predicted to decrease even more dramatically, by 82%, when taken with rifampicin, indicating a significant risk of reduced efficacy for both antiretrovirals in patients also receiving this tuberculosis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Drug-Drug Interactions Between Rifampicin and Long-Acting Cabotegravir and Rilpivirine Using Physiologically Based Pharmacokinetic Modeling. Rajoli, RKR., Curley, P., Chiong, J., et al.[2021]

In a study of 1,752 HIV-positive patients, 31.2% were found ineligible for the injectable treatment of cabotegravir and rilpivirine due to factors like detectable viral load and history of virological failures.

The proportion of ineligible patients increased to 47.3% when considering those with complete resistance test data, highlighting significant barriers to the feasibility of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are we ready for long-acting? A feasibility evaluation of long-acting cabotegravir-rilpivirine in clinical practice. Borghetti, A., Farinacci, D., Ciccullo, A., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39853281/

Efficacy, Safety and Retention in Care Among Adolescents ... Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) can improve adherence among adolescents and youth with HIV (AYHIV).

2. viivhealthcare.com viivhealthcare.com/en-us/media-center/news/press-releases/2025/july/daily-pills-after-achieving-rapid-viral-suppression/

ViiV Healthcare data show 89% of treatment-naïve people ... Study results showed that participants achieved rapid viral suppression with DTG/3TC (median time to suppression: 4.14 weeks), following which ...

3. cabenuvahcp.com cabenuvahcp.com/efficacy-and-safety/beyond/

BEYOND Real-World Study Data | CABENUVA (cabotegravir BEYOND, a real-world study of patients receiving CABENUVA (N=233), observed high rates of viral suppression through Month 24:* · At year 1, 2% (3/156) had an HIV ...

4. academic.oup.com academic.oup.com/ofid/article/12/5/ofaf220/8116433

Clinical Outcomes and Perspectives of People With Human ... Participants receiving long-acting cabotegravir plus rilpivirine experienced high rates of virologic suppression and a low rate of ...

5. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/pediatric-arv/drug-information-integrase-inhibitors-cabotegravir-pediatric-arv.pdf

Pediatric Antiretroviral Drug Information – Cabotegravir Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, Phase 3.

6. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2021/october/viiv-healthcare-presents-positive-interim-data-showing/

ViiV Healthcare presents positive interim data showing ... The CARISEL study showed most people living with HIV who started treatment felt positive about the long-acting regimen, a sentiment shared by healthcare teams.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213970/

Safety and pharmacokinetics of oral and long-acting ... Study findings showed that approved adult dosing of CAB-LA or RPV-LA (every 4 or every 8 weeks) in adolescents achieved comparable exposure to ...