Injectable Cabotegravir + Rilpivirine for HIV

Not currently recruiting at 123 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must be taking: Integrase inhibitors

Must not be taking: Antidepressants, Anticoagulants

Disqualifiers: Pregnancy, Hepatitis B, Seizures, 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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a long-acting injectable treatment can maintain HIV-1 control in individuals currently managing their condition with daily oral medication. It will compare the effectiveness of two injectable drugs, cabotegravir (CAB or Vocabria) and rilpivirine, administered monthly, against the standard oral treatment of abacavir, dolutegravir, and lamivudine. The trial seeks participants who have HIV-1, are new to antiretroviral therapy, and have maintained viral suppression with current medication. Participants will initially take the current oral treatment before potentially switching to the injectable regimen if they qualify. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require participants to switch from their current HIV treatment to the study medications. You should discuss your specific situation with the study team.

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

Research has shown that the combination of long-acting cabotegravir and rilpivirine is generally well-tolerated by people with HIV. In earlier studies, most participants experienced only mild to moderate side effects. Common side effects included reactions at the injection site, such as pain or redness, which usually didn't last long. Serious side effects were rare.

One study found that administering these drugs every two months maintained consistent safety over 96 weeks. This suggests the treatment is safe for long-term use. Consistent safety results across different studies increase confidence in the treatment's safety for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for HIV?

Researchers are excited about the injectable combination of Cabotegravir and Rilpivirine for HIV because it offers a new delivery method: long-acting injections every four weeks. Unlike standard oral treatments, which require daily pills like Biktarvy or Triumeq, this approach could simplify regimens and improve adherence. The long-acting nature of these injections also means potentially fewer side effects related to daily dosing and greater convenience for patients, as they don't need to remember a daily medication. This could be a game-changer in managing HIV, especially for those who struggle with maintaining a consistent daily pill routine.

What evidence suggests that this trial's treatments could be effective for HIV?

This trial will compare the effectiveness of long-acting injections of cabotegravir and rilpivirine with daily oral treatment. Studies have shown that long-acting injections of cabotegravir and rilpivirine effectively control HIV-1. Specifically, over 85% of patients who switched to these injections maintained low virus levels after 48 weeks. This outcome is similar to daily pills but offers the convenience of monthly injections. The virus remains at very low levels, indicating effective treatment. Additionally, long-acting injections increase patient satisfaction by reducing the need for daily pills. ^{6 7 8 9 10}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Are You a Good Fit for This Trial?

Adults with HIV-1 who haven't been treated for it before can join this trial. They must have a certain level of virus in their blood and be able to consent to the study's rules. Women can't be pregnant or breastfeeding, and everyone must meet specific contraception requirements. People with severe allergies to study drugs, serious health conditions, or those at risk of suicide are not eligible.

Inclusion Criteria

I am not pregnant, not breastfeeding, and follow the required birth control guidelines.

I have taken HIV medication for 10 days or less since my diagnosis.

I am able to understand and willing to sign the consent form for the trial.

Exclusion Criteria

Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the participant's participation in the study of an investigational compound

I do not have liver disease, cirrhosis, pancreatitis, or biliary abnormalities.

Everyone will be tested for syphilis using a blood test called rapid plasma reagin (RPR).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive ABC/DTG/3TC for 20 weeks to achieve virologic suppression

20 weeks

Maintenance

Participants are randomized to either continue ABC/DTG/3TC or switch to oral CAB + RPV for 4 weeks, followed by monthly CAB LA + RPV LA injections

48 weeks

Monthly visits for injections

Extension

Participants who complete Week 100 and remain virologically suppressed may opt into the Extension Phase with continued monthly injections

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir
• Rilpivirine

Trial Overview

The FLAIR study is testing if a long-acting injectable combo (cabotegravir and rilpivirine) keeps HIV suppressed as well as a daily pill regimen does after initial treatment success. Participants will first take pills for 20 weeks; then they'll either continue pills or switch to monthly injections for up to 100 weeks.

How Is the Trial Designed?

Group I: CAB LA + RPV LA every 4 weeks Experimental Treatment 4 Interventions

After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.

Group II: ABC / DTG / 3TC (600 mg/50mg/300mg) once daily Active Control 2 Interventions

After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing at either Week 100 (direct to inject) or Week 104b (if using optional oral lead-in with CAB 30 mg + RPV 25 mg once daily).

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

Approved in European Union as Vocabria for:

• HIV-1 infection

Approved in United States as Vocabria for:

• HIV-1 infection

Approved in Canada as Vocabria for:

• HIV-1 infection

Approved in Japan as Vocabria for:

• HIV-1 infection

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

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

Cabotegravir and rilpivirine, as long-acting injectable therapy for HIV-1, have shown to be non-inferior to traditional oral triple-therapy in phase II and III trials, indicating their effectiveness as a treatment option.

Patients generally accept the 4-weekly or 8-weekly injections despite some experiencing injection-site reactions, but there are still important questions regarding missed doses, drug interactions, and the therapy's efficacy across different HIV-1 subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. Fernandez, C., van Halsema, CL.[2020]

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-rilpivirine (CAB-RPV) significantly improves viral suppression rates in people with HIV who have adherence challenges, achieving 60% suppression at 3 months compared to only 13% with standard oral treatment.

In a model projecting outcomes over 3 years, CAB-RPV combined with supportive services is expected to lead to a 44% viral suppression rate and a life expectancy of 9.4 years, outperforming both standard oral treatments and those with additional support services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. Chen, W., Gandhi, M., Sax, PE., 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]

In a study of 321 adults with HIV receiving the CAB + RPV LA injectable regimen, 90% of continuation injections were administered on time, indicating strong adherence to the injection schedule.

Among those who started with a viral load < 50 copies/mL, 95% remained undetectable and 99% were suppressed at their last measurement, demonstrating the high efficacy of CAB + RPV LA in maintaining virologic control in routine clinical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. Sension, MG., Brunet, L., Hsu, RK., et al.[2023]

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a Real-World Setting: Effectiveness, Adherence to Injections, and Patient-Reported. Outcomes From People With HIV-1 in the German CARLOS Study.

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Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of ...

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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).

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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.

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ViiV Healthcare presents data for long-acting cabotegravir ...

ATLAS-2M met its primary endpoint at Week 48, demonstrating that the efficacy of long-acting cabotegravir and rilpivirine dosed every 2-months (every eight ...