Long-Acting Cabotegravir + rHuPH20 for HIV Infection

Recruiting at 3 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: ViiV Healthcare

Must not be taking: Anticoagulants, Drugs of abuse

Disqualifiers: Cardiovascular, Liver disease, HIV, others

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

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 78 weeks

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a long-lasting HIV medication called Cabotegravir, given as an injection. It also tests if adding rHuPH20 helps the medication spread better in the body. The study focuses on people who need long-term HIV treatment. Cabotegravir is the first long-acting injectable treatment option approved for adults with HIV-1.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Long-Acting Cabotegravir + rHuPH20 for HIV infection?

Long-acting cabotegravir, when used with rilpivirine, has been shown to effectively manage HIV by maintaining undetectable viral loads in patients who were already virologically suppressed. It is also promising for HIV prevention, as it provides prolonged drug exposure, which can improve adherence and treatment success. ^{1 2 3 4 5}

Is long-acting cabotegravir safe for humans?

Long-acting cabotegravir has been shown to have a manageable safety profile in clinical trials, both for treating HIV and as a preventive measure. It is generally well-tolerated, with fewer issues related to kidney function compared to some other HIV medications. ^{1 2 6 7 8}

What makes the drug Cabotegravir unique for HIV treatment?

Cabotegravir is unique because it is a long-acting injectable drug that can be administered every 4 weeks or less, reducing the need for daily pills and potentially improving adherence to treatment. It is used in combination with rilpivirine and is the first long-acting injectable option approved for people with HIV-1 who are already virologically suppressed. ^{1 2 3 4 5}

Research Team

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Eligibility Criteria

Healthy adults aged 18-55, with a body weight of at least 40 kg and BMI between 18-32 kg/m^2. Participants must test negative for SARS-CoV-2 twice before dosing, use contraception according to local guidelines, and not have used tobacco or nicotine products within the last three months.

Inclusion Criteria

Participants who are negative on two (2) consecutive tests for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one performed prior to admission to the Phase 1 unit (up to Day 7 prior to admission) and one prior to dosing, i.e., on Day -1 or Day 1.

I am between 18 and 55 years old.

I weigh at least 40 kg and my BMI is between 18 and 32.

Exclusion Criteria

Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).

I have had COVID-19 symptoms or contact with a COVID-19 positive person in the last 14 days.

My hemoglobin level is below the normal range for my gender.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single subcutaneous or intramuscular administration of long-acting Cabotegravir with or without Recombinant Human Hyaluronidase PH20, and single-dose or repeat-dose IM administration of rilpivirine

Up to 78 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cabotegravir
• Recombinant human hyaluronidase PH20 (rHuPH20)

Trial Overview The trial is testing the safety and how the body processes long-acting Cabotegravir (CAB) given by injection at different strengths (200 mg/mL and 400 mg/mL), with and without an enzyme called rHuPH20. Part A has been closed based on preliminary results.

Participant Groups

Group I: Part E: Participants receiving RPV Experimental Treatment 1 Intervention

Group II: Part D: Participants receiving CAB >=400 mg/mL with rHuPH20 Experimental Treatment 2 Interventions

Group III: Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I Experimental Treatment 2 Interventions

Group IV: Part A: Participants receiving CAB 200 mg/mL with rHuPH20 Experimental Treatment 2 Interventions

Part A of the study (CAB 200 mg/mL with rHuPh20) has been closed to further enrolment based on preliminary results.

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 Sciences Ireland Unlimited Company

Collaborator

Trials

1

Recruited

180+

Findings from Research

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]

Cabotegravir long-acting injectable (CAB LA) was found to be well tolerated among participants, with a high completion rate of injections (80% in Cohort 1 and 92% in Cohort 2), despite common injection site reactions (ISRs) that were mostly mild to moderate.

The study demonstrated that CAB LA 600 mg administered every 8 weeks successfully maintained drug levels above effective thresholds in 95% of participants, supporting its potential for HIV prevention and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. Landovitz, RJ., Li, S., Grinsztejn, B., et al.[2023]

Long-acting cabotegravir/rilpivirine (CAB/RPV) was effective in achieving undetectable HIV RNA levels in a patient with a history of virologic failure within just two months of treatment initiation.

The case also highlights the occurrence of immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium-intracellulare infection after starting CAB/RPV, indicating that while the treatment is effective, it can lead to complications in patients with underlying infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. Al-Handola, R., Chinnappan, J., Bakeer, M., et al.[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]

Cabotegravir, a new integrase strand transfer inhibitor, shows promise as a long-acting injectable treatment for HIV, potentially improving adherence to pre-exposure prophylaxis (PrEP) and treatment due to reduced dosing frequency.

Clinical studies indicate that cabotegravir can be effectively used alone or in combination with other anti-HIV agents like rilpivirine, allowing for formulations that require administration every 4 weeks or less, which may enhance patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A literature review of the patent application publications on cabotegravir - an HIV integrase strand transfer inhibitor. Kovač, L., Časar, Z.[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]

In a Phase 2b study involving 97 adults living with HIV-1, the long-acting formulation of cabotegravir and rilpivirine (CAB+RPV) administered every 2 months successfully maintained virologic suppression, with no participants showing HIV-1 RNA levels above 50 copies/ml after 12 months.

The long-acting CAB+RPV treatment had a favorable safety profile, with no new safety concerns identified, and 88% of participants preferred this regimen over their previous daily oral treatment, indicating high treatment satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. Mills, A., Richmond, GJ., Newman, C., et al.[2023]

Long-acting cabotegravir is more effective than daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in preventing HIV infection, with a significantly lower risk of infection (HR = 0.22).

Cabotegravir also shows a better safety profile, with less frequent decreases in kidney function (creatinine clearance) compared to TDF-FTC, although it may cause more injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis. Chen, X., Li, J., Kou, L., et al.[2023]

References

1. 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]

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

Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. [2023]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

A literature review of the patent application publications on cabotegravir - an HIV integrase strand transfer inhibitor. [2020]

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

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

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

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis. [2023]