Cabotegravir + Rilpivirine Injections for HIV/AIDS

Recruiting at 110 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must be taking: Antiretrovirals

Must not be taking: Anticoagulants, Etravirine

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

Duration: 52 weeks

618 Participants Needed

Trial Summary

What is the purpose of this trial?

The Antiretroviral Therapy as Long Acting Suppression (ATLAS) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult subjects with current viral suppression on a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent, remain suppressed upon switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). This is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, antiretroviral therapy (ART)-adult subjects who are stably suppressed on a current antiretroviral (ARV) regimen. 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 (Q4W: monthly) compared with maintenance of current ARV regimen containing 2 NRTIs plus an INI, NNRTI, or a PI. Eligible subjects will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue current ART or switch to initiate oral therapy with CAB 30 mg + RPV 25 mg once daily for 4 Weeks followed by Q4 weekly (monthly) CAB LA + RPV LA injections. Following the Maintenance phase at Week 52, subjects who were randomized to continue their current ART regimen will be given an option to switch to CAB LA + RPV LA injections. Those subjects would transition to LA dosing, beginning with 4 weeks oral CAB + RPV therapy at Week 52, and receive the first IM CAB LA + RPV LA injections at Week 56.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it involves switching from your current HIV treatment to a new regimen of cabotegravir and rilpivirine injections. You may need to stop your current antiretroviral therapy if you are selected to switch to the new treatment.

What data supports the effectiveness of the drug Cabotegravir + Rilpivirine for HIV/AIDS?

Research shows that the combination of cabotegravir and rilpivirine as long-acting injections is effective in maintaining HIV-1 viral suppression, similar to traditional oral therapies. It is particularly beneficial for people who have trouble sticking to daily oral medication, as it requires less frequent dosing. ^{1 2 3 4 5}

Is the combination of Cabotegravir and Rilpivirine safe for humans?

Cabotegravir and Rilpivirine injections are generally considered safe for humans, with studies showing they are well-tolerated despite frequent injection-site reactions. These injections have been tested in clinical trials for HIV treatment, and while they are effective, some challenges like managing missed doses and drug interactions remain. ^{1 2 4 5 6}

What makes the Cabotegravir + Rilpivirine treatment unique for HIV/AIDS?

Cabotegravir and Rilpivirine offer a unique long-acting injectable option for HIV treatment, allowing patients to receive injections every 4 to 8 weeks instead of taking daily pills. This can be particularly beneficial for those who have difficulty adhering to daily oral medication regimens. ^{1 2 4 5 6}

Research Team

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Eligibility Criteria

Adults over 18 with HIV-1 who've been on a stable antiretroviral regimen for at least 6 months, showing viral suppression. They must not be pregnant or breastfeeding and agree to use effective contraception. Excluded are those with certain medical conditions, history of specific drug use, or participation in other trials.

Inclusion Criteria

I have been on my current HIV medication for at least 6 months without changing it due to treatment failure.

My HIV treatment regimen has been stable before screening.

Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening

Exclusion Criteria

I need long-term blood thinners, with some exceptions.

I am not currently taking any medications or have a treatment history that would exclude me.

My HIV viral load has been mostly under control, with one or two increases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral CAB 30 mg + RPV 25 mg once daily for 4 weeks, followed by monthly CAB LA + RPV LA injections

52 weeks

Monthly visits for injections

Extension

Participants who continued their current ART regimen have the option to switch to CAB LA + RPV LA injections

4 weeks oral therapy followed by injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cabotegravir
• Rilpivirine

Trial Overview The trial tests if switching from current antiretrovirals to long-acting injections of Cabotegravir and Rilpivirine maintains virus suppression. Participants will either continue their current treatment or switch after an initial oral phase, comparing the efficacy of both methods.

Participant Groups

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

Eligible subjects receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 onwards subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks until withdrawal.

Group II: Current antiretroviral regimen Active Control 1 Intervention

Eligible subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm.

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

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

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Findings from Research

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. [2022]

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

Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. [2023]

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

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

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

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. [2023]

6. 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]