Cabotegravir + Rilpivirine for HIV in Children

Recruiting at 13 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

Trial Summary

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 Cabotegravir + Rilpivirine safe for children with HIV?

Cabotegravir and rilpivirine have been approved as a long-acting injectable treatment for HIV in adults, showing encouraging safety results. However, there is limited data on their safety in children, and certain groups, like pregnant women, were excluded from studies due to lack of data. ^{1 2 3 4 5}

What makes the drug Cabotegravir + Rilpivirine unique for treating HIV?

Cabotegravir and Rilpivirine is unique because it is the first long-acting injectable treatment for HIV, allowing patients to receive injections every two months instead of taking daily pills, which can improve convenience and adherence to the treatment. ^{1 3 6 7 8}

What is the purpose of this trial?

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Are we ready for long-acting? A feasibility evaluation of long-acting cabotegravir-rilpivirine in clinical practice. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Predicting Drug-Drug Interactions Between Rifampicin and Long-Acting Cabotegravir and Rilpivirine Using Physiologically Based Pharmacokinetic Modeling. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Impact of rilpivirine cross-resistance on long-acting cabotegravir-rilpivirine in low and middle-income countries. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Cabotegravir Plus Rilpivirine: First Approval. [2021]

6. England 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. Italy pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. [2023]