CABENUVA for HIV

(CAPRI Trial)

Overseen By Paige E Rutter

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Torsade de Pointes

Disqualifiers: Hepatitis B, Severe hepatic impairment, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new HIV treatment called CABENUVA, which combines two long-acting medications, Cabotegravir and Rilpivirine (CAB + RPV), to evaluate its effectiveness and safety for people with HIV who also have severe kidney problems. The study targets individuals whose HIV is under control but who have serious kidney issues (chronic kidney disease stages 4 or 5) and might be receiving dialysis. Those with stable HIV treatment and no recent high viral load (amount of virus in the blood) may qualify. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for HIV patients with kidney issues.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that decrease CABENUVA concentrations at least four weeks before starting the study. Other prohibited medications should be stopped at least two weeks before starting. If you are on any prohibited medications and cannot switch to an alternative, you may not be eligible to participate.

Is there any evidence suggesting that CABENUVA is likely to be safe for humans?

Research has shown that Long-acting Cabotegravir (CAB) and Rilpivirine (RPV) are generally well-tolerated. People who used this treatment for over two years successfully managed their HIV, experiencing few side effects. Some studies also found slight improvements in kidney function when switching to this treatment from other medications. Although researchers are still collecting long-term data, these results suggest that CAB and RPV are safe for most people, with few negative effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Researchers are excited about CABENUVA for HIV because it offers a new approach for people with severe renal impairment. Unlike standard treatments that often require daily oral medication, CABENUVA is a long-acting injectable combining cabotegravir (CAB) and rilpivirine (RPV), administered monthly and then every two months. This regimen could significantly reduce the treatment burden for patients, making it easier for them to adhere to their medication schedule. Additionally, the injectable format bypasses issues related to gastrointestinal absorption, which can be a concern with oral medications.

What evidence suggests that CABENUVA might be an effective treatment for HIV with severe renal impairment?

Research shows that CABENUVA, a combination of two long-acting medications, Cabotegravir (CAB) and Rilpivirine (RPV), effectively controls the HIV virus. In this trial, participants with severe renal impairment, including those requiring hemodialysis, will receive CABENUVA to evaluate its effectiveness in maintaining low virus levels, crucial for managing HIV. Some small studies suggest that switching to CABENUVA from other treatments might slightly improve kidney function. These findings support CABENUVA as a reliable option for people with HIV and severe kidney issues. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with HIV and severe renal impairment can join this trial if they've been on a stable HIV treatment for at least 6 months, have undetectable viral loads, and use effective contraception. Pregnant or breastfeeding women, those planning to become pregnant, individuals with unstable kidney disease or severe liver issues are excluded.

Inclusion Criteria

I am on standard HIV-1 treatment and meet all required criteria.

I am not pregnant, not breastfeeding, and meet the fertility criteria.

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to during the study.

My condition did not improve with initial treatments.

Participants with evidence of active Hepatitis B virus (HBV) infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CABENUVA monthly for 6 months followed by every 2 months for 6 months

12 months

Monthly visits for the first 6 months, then every 2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CAB + RPV

Trial Overview The study is testing the effectiveness and safety of CABENUVA (Cabotegravir plus Rilpivirine) in patients with HIV who also have serious kidney problems. It's research to see how well these long-acting drugs work and how tolerable they are for participants.

How Is the Trial Designed?

Group I: HIV + severe renal impairment Experimental Treatment 1 Intervention

CAB LA + RPV LA administered to HIV virologically suppressed participants with CKD stage 4/5 (CrCl \< 30 mL/min) with (n = 6) or without (n = 6) hemodialysis receiving CABENUVA monthly for 6 months followed by every 2 months for 6 months.

Who Is Running the Clinical Trial?

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Lead Sponsor

Trials

52

Recruited

13,000+

Published Research Related to This Trial

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]

Cabenuva is the first complete injectable therapy for adults with HIV-1, combining cabotegravir and rilpivirine, and is administered once a month after an initial month of oral treatment.

This innovative treatment offers a new option for HIV management, potentially improving adherence and convenience for patients compared to daily oral medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Extended-Release Injectable Drug Therapy for HIV. Aschenbrenner, DS.[2023]

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]

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 (cabotegravir/rilpivirine) is a long-acting injectable treatment for HIV that has shown equal effectiveness to traditional oral antiretroviral therapy in maintaining HIV-1 suppression, based on major clinical trials like ATLAS and FLAIR.

The ATLAS-2 M study demonstrated that administering Cabenuva every 8 weeks is just as effective as every 4 weeks, which can improve patient adherence and reduce the stigma associated with frequent treatment, while also minimizing risks of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir/Rilpivirine: the last FDA-approved drug to treat HIV. Taki, E., Soleimani, F., Asadi, A., et al.[2022]

Cabotegravir/rilpivirine (CAB/RPV) is the first complete injectable antiretroviral therapy approved for HIV treatment, offering a monthly intramuscular injection option that improves adherence compared to daily oral medications.

Clinical trials have shown CAB/RPV to achieve high rates of sustained viral suppression with a favorable safety profile, while also enhancing patient satisfaction due to its convenience and confidentiality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. Howe, ZW., Norman, S., Lueken, AF., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2590059525000962

Long-Acting Cabotegravir and Rilpivirine Treatment for HIV ... Small studies have shown modest improvements in kidney function after switching to LA-CAB/RPV from a tenofovir-based ART regimen. ... Similarly, rilpivirine did ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12372666/

Long-Acting Cabotegravir and Rilpivirine in Patients With ... Current data support CAB + RPV LA use in renal impairment [17], including in hemodialysis [11]. No differences have been found in patients ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12390647/

Safety, Tolerability, and Metabolic Effects of Long-Acting ... Several pivotal clinical trials have demonstrated the effectiveness of LA CAB/RPV in maintaining virological suppression, showing non- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03299049

NCT03299049 | Efficacy, Safety and Tolerability Study of ... A sub-study in the ATLAS-2M study will evaluate the pharmacokinetics, tolerability and efficacy of CAB and RPV long acting injections following ...

5. trial.medpath.com trial.medpath.com/clinical-trial/c5c3d5400564daa2/nct05601128-cabenuva-hiv-1-renal-impairment-study

A Study Evaluating the Pharmacokinetics, Efficacy, Safety and ... The purpose of this study is to evaluate the efficacy and safety of CABENUVA (Long-acting Cabotegravir Plus Long-acting Rilpivirine) in patients with HIV ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12339819/

Long-Term Real-World Use of Cabotegravir/Rilpivirine Despite increasing use of LA-CAB/RPV, long-term real-world data on durability, adherence, and virological outcomes remain limited to 2 years.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05601128

NCT05601128 | A Study Evaluating the Pharmacokinetics, ... The purpose of this study is to evaluate the efficacy and safety of CABENUVA (Long-acting Cabotegravir Plus Long-acting Rilpivirine) in patients with HIV ...