CAB LA + RPV LA for HIV Infection

(CROWN Trial)

Recruiting at 34 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study will assess how effective, safe, and long-lasting a long-acting antiretroviral therapy (ART) using CAB LA + RPV LA is for people with HIV who still have detectable virus levels despite being on oral ART. The study will also consider feedback from patients on their experience with this 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 CAB LA + RPV LA safe for humans?

CAB LA and RPV LA have been generally well-tolerated in clinical trials, with safety profiles similar to placebo, meaning they didn't cause more side effects than a harmless substance. They are considered safe for use in preventing and treating HIV, but more research is needed to confirm these findings, especially for RPV LA. ^{1 2 3 4 5}

What makes the drug CAB LA + RPV LA unique for treating HIV?

CAB LA + RPV LA is unique because it is a long-acting injectable treatment for HIV, which means it is administered less frequently compared to daily oral medications, potentially improving adherence and convenience for patients. ^{6 7 8 9 10}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• CAB LA + RPV LA (Antiretroviral)

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.

Participant Groups

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

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]

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]

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]

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. England pubmed.ncbi.nlm.nih.gov

Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention? [2023]

3. Switzerland 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. [2021]

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

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment? [2023]

5. England 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. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Viral hepatitis and HIV coinfection. [2008]

7. England pubmed.ncbi.nlm.nih.gov

Liver transplantation in HIV/hepatitis co-infection. [2021]

8. United States 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. [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Liver transplantation for patients infected with both HIV and HCV or HIV and HBV]. [2007]

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

Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation. [2007]