CAB LA + RPV LA for HIV Infection

(CROWN Trial)

Recruiting at 51 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must be taking: Oral ART

Must not be taking: Anti-coagulants, TdP drugs

Disqualifiers: Pregnancy, Hepatitis B, Hepatitis C, 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: 1

Duration: 24 months

332 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new long-acting antiretroviral therapy (ART) for people with HIV who still have detectable virus levels despite taking oral ART. Researchers aim to determine if CAB LA and RPV LA injections are effective, safe, and provide long-lasting results. Participants will either continue their current oral ART or switch to the new long-acting injection to compare outcomes. People with HIV who haven't seen much improvement with their current oral treatment might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

Participants must continue taking their current oral antiretroviral therapy (ART) regimen until about one week after the Month 6 visit. The trial does not specify stopping other medications, but certain medications are prohibited, such as those associated with Torsades de Pointes or chronic anti-coagulants.

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

Research has shown that the combination of CAB LA (cabotegravir long-acting) and RPV LA (rilpivirine long-acting) is generally safe and well-tolerated for people with HIV. Studies have found that the most common side effects occur at the injection site and are usually mild and not serious. Evidence indicates high rates of virologic suppression, meaning the treatment effectively controls the virus. Overall, the data suggests that individuals who switch to this treatment experience good outcomes and tolerate it well. ^{1 2 3 4 5}

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

Researchers are excited about CAB LA + RPV LA for HIV infection because it offers a long-acting alternative to daily oral antiretroviral therapy (ART). Unlike standard treatments that require daily pills, CAB LA + RPV LA involves injections given once every two months, which could improve convenience and adherence for patients. This new delivery method could reduce the burden of daily medication, making it easier for people to manage their HIV treatment over the long term.

What evidence suggests that CAB LA + RPV LA might be an effective treatment for HIV?

Research has shown that combining CAB LA (long-acting cabotegravir) and RPV LA (long-acting rilpivirine) effectively treats HIV. One study found that 87% of participants successfully reduced their virus levels, with most adhering to their injection schedule. In real-world use, only a small number (0.8%) experienced unexpected treatment failure. Participants reported greater satisfaction with this treatment compared to previous ones. In this trial, participants in the CAB LA + RPV LA group will receive initial injections on Day 1 and Month 1, followed by maintenance injections every two months for up to 24 months. This suggests CAB LA + RPV LA is a promising option for people with HIV who still have detectable virus levels despite taking oral treatments. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with HIV who are currently on oral antiretroviral therapy (ART) but still have detectable levels of the virus. Specific eligibility details are not provided, so it's best to contact the study organizers for more information.

Inclusion Criteria

I am currently on oral ART and willing to keep taking it.

I am 12 years or older and weigh at least 35 kg.

Informed consent/Assent provided as per study protocol

Exclusion Criteria

I have used CAB, need long-term blood thinners, or take medications linked to heart rhythm issues.

I have not recently used experimental drugs or vaccines.

I have severe liver problems and am being treated for hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive initial injections of CAB LA + RPV LA at Day 1 and Month 1, followed by maintenance injections every 2 months for up to 24 months

24 months

Initial injections at Day 1 and Month 1, then every 2 months

Follow-up

Participants are monitored for virologic suppression and adverse events

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• CAB LA + RPV LA

Trial Overview The effectiveness and durability of a long-acting injectable ART regimen using Cabotegravir (CAB LA) and Rilpivirine (RPV LA) is being tested in participants whose HIV remains detectable despite current treatment.

How Is the Trial Designed?

Group I: CAB LA + RPV LA Group Experimental Treatment 1 Intervention

Participants receive initial injections at Day 1 and Month 1, followed by maintenance injections every 2 months for up to 24 months.

Group II: Oral ART Control Group Active Control 1 Intervention

Participants continue to take their current oral ART for 6 months, including a final dose at their first injection visit.

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Published Research Related to This Trial

Long-acting injectable pre-exposure prophylaxis (LAI PrEP) with cabotegravir (CAB-LA) and rilpivirine (RPV-LA) was found to be generally well-tolerated, with safety profiles similar to placebo across eight studies involving 666 participants.

Pharmacokinetic analyses indicated that CAB-LA 600 mg administered every 8 weeks was more effective than 800 mg every 12 weeks, and RPV-LA 1200 mg every 8 weeks showed superior results over other dosing regimens, suggesting promising efficacy in preventing HIV-1 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials. Lazarus, G., Wangsaputra, VK., Christianto, ., et al.[2021]

Individuals at high risk for HIV are also at risk for hepatitis B (HBV) and hepatitis C (HCV) infections, which can complicate HIV treatment and increase liver disease morbidity and mortality.

Expert guidelines recommend that all HIV-infected individuals be screened for HBV and HCV, and appropriate management strategies should be implemented, including the use of specific antiviral treatments that may also target both HIV and HBV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viral hepatitis and HIV coinfection. Sulkowski, MS.[2008]

HIV-infected patients with end-stage liver disease (ESLD) have a one-year survival rate of only 50-55%, but liver transplantation is now a viable option for these patients, with mid-term survival rates similar to those of HIV-negative patients.

Post-transplant challenges include interactions between antiretroviral and immunosuppressive medications, as well as the recurrence of hepatitis C virus (HCV) infection, which significantly impacts survival, especially in HIV-HCV co-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver transplantation in HIV/hepatitis co-infection. Miro, JM., Aguero, F., Laguno, M., et al.[2021]

Liver transplantation in patients coinfected with HIV and hepatitis viruses (HBV or HCV) is feasible, with 2-year survival rates of 70% for HIV-HCV and 100% for HIV-HBV patients, showing that HIV infection is no longer a contraindication for this procedure.

While there is effective prevention of HBV recurrence post-transplant, HCV recurrence is a significant challenge, occurring more rapidly and severely in HIV coinfected patients, highlighting the need for better understanding and management strategies for HCV after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Liver transplantation for patients infected with both HIV and HCV or HIV and HBV]. Duclos-Vallée, JC., Teicher, E., Vittecoq, D., et al.[2007]

Long-acting injectable antiretroviral (ARV) treatments, like cabotegravir/rilpivirine (LA-CAB/RPV), offer a simplified alternative to daily oral medications for HIV, potentially improving adherence and health outcomes for patients.

LA-CAB/RPV is currently the only approved long-acting injectable regimen for HIV treatment in adults and adolescents who are already virologically suppressed, with ongoing studies exploring its use in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment? Brizzi, M., Pérez, SE., Michienzi, SM., et al.[2023]

In a study of 35 HIV-HBV coinfected patients referred for liver transplantation, 67% had lamivudine-resistant HBV, which was associated with a high risk of liver-related death before transplantation.

Among those who underwent transplantation, all patients successfully maintained undetectable HBV levels post-transplant with a combination of hepatitis B immune globulin and antiviral therapy, indicating effective prevention of HBV recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation. Terrault, NA., Carter, JT., Carlson, L., et al.[2007]

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 1301 HIV/HBV-coinfected patients over 14,882 person-years, those diagnosed after 2003 had a 50% lower risk of all-cause mortality compared to those diagnosed before 2003, indicating significant improvements in patient outcomes due to advancements in treatment.

The use of tenofovir-containing regimens was linked to a reduced risk of both all-cause and liver-related mortality, highlighting its importance as a recommended treatment for HIV/HBV-coinfected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased All-Cause and Liver-Related Mortality Risk in HIV/Hepatitis B Virus Coinfection Coinciding With the Introduction of Tenofovir-Containing Combination Antiretroviral Therapy. van Welzen, BJ., Smit, C., Boyd, A., et al.[2022]

Long-acting injectable cabotegravir (CAB-LA) is a promising new option for HIV prevention, showing high safety and efficacy in clinical trials, particularly for individuals struggling with adherence to oral PrEP.

Despite its potential, challenges such as breakthrough infections, logistical issues, and the need for comprehensive implementation strategies must be addressed to fully integrate CAB-LA into HIV prevention programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention? Liegeon, G., Ghosn, J.[2023]

In a study of 25 pregnancies involving women exposed to cabotegravir and rilpivirine (CAB + RPV), there were 10 live births, indicating that these medications can be used during conception with monitored outcomes.

The plasma levels of CAB and RPV during pregnancy were similar to those found in non-pregnant women, suggesting that the pharmacokinetics of these drugs remain stable and safe during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy outcomes and pharmacokinetics in pregnant women living with HIV exposed to long-acting cabotegravir and rilpivirine in clinical trials. Patel, P., Ford, SL., Baker, M., et al.[2023]

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40204512/

Efficacy of long-acting cabotegravir plus rilpivirine in ... The cumulative probability of achieving virologic success was 87% (79%-95%). Most patients maintained adherence rates above 90% to their scheduled injection ...

3. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/july/long-acting-injectables-for-hiv-at-ias-2025/

ViiV Healthcare presents new data demonstrating positive ... 24-month outcomes of cabotegravir+rilpivirine long-acting every 2 months in a real‑world setting: effectiveness, adherence to injections, and ...

4. viivexchange.com viivexchange.com/content/dam/cf-viiv/viivexchange/medical/pdf/aids-2024-pozniak-combine-util-and-adher-tupec278-disc.pdf

Real-World Utilization and Effectiveness of Long-Acting ... Three individuals (0.8%) had confirmed virologic failure (CVF) after initiation of CAB+RPV LA. Real-World Utilization and Effectiveness of Long-Acting ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1341321X2500131X

Efficacy and safety of switching to long-acting cabotegravir ... Mean (SD) HIVTSQs treatment satisfaction scores of Japanese participants showed greater improvement from baseline to Month 12 in the CAB+RPV LA group (+6.25 [ ...

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

Safety, Tolerability, and Metabolic Effects of Long-Acting ... Clinical trial data suggest that LA CAB/RPV is generally safe and well tolerated. The most common side effects were injection site reactions, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02951052

NCT02951052 | Study Evaluating the Efficacy, Safety, and ... This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks.