Long-Acting Cabotegravir + rHuPH20 for HIV Infection

Recruiting at 2 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Cabotegravir to assess its safety and tolerability for people with HIV. Researchers aim to understand how the body processes this medication when administered either under the skin or into a muscle. The trial compares different formulations of Cabotegravir and another drug, Rilpivirine. Healthy, HIV-negative individuals without a history of certain health conditions might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that cabotegravir, the drug used in this trial, has undergone safety testing in various situations. Studies indicate that injectable cabotegravir is generally safe and effective for preventing HIV, with few safety concerns. The FDA has approved it for HIV prevention, confirming its strong safety record.

The trial also uses rHuPH20, a substance that enhances the delivery of medications under the skin. Early research suggests that combining rHuPH20 with cabotegravir is safe and allows the drug to remain in the body longer without major issues.

Additionally, the trial includes rilpivirine, another medication for treating HIV. Rilpivirine is already approved and is generally well-tolerated by patients.

In summary, while this trial is still in its early stages, the treatments being tested have demonstrated good safety records in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about long-acting Cabotegravir for HIV infection because it offers a new way to manage the condition with less frequent dosing. Unlike current daily oral medications like tenofovir or emtricitabine, Cabotegravir can be administered as an injection, potentially only once a month or even less often. This long-acting approach could significantly improve adherence to treatment and provide more convenience for people living with HIV. Additionally, the use of rHuPH20 aims to enhance the absorption and effectiveness of Cabotegravir.

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

Studies have shown that long-acting cabotegravir (CAB) effectively treats HIV. Real-world studies report that CAB prevents HIV infections with over 99% effectiveness. In this trial, some participants will receive CAB with rHuPH20, a substance that enhances drug distribution in the body, potentially extending the time between doses. This means fewer injections while maintaining effectiveness. Other participants will receive different formulations or combinations, such as CAB with rilpivirine, which helps control the virus. Overall, existing evidence supports CAB's strong potential in effectively managing HIV. ^{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?

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

Capable of giving written informed consent.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Group II: Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I or CAB Formulation J Experimental Treatment 3 Interventions

Group III: 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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40604367/

Patient-reported outcomes in clinical trials assessing the ... This systematic review explores the role of CAB + RPV-LA injectables in antiretroviral therapy (ART), with a focus on patient-reported outcomes from five key ...

2. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/october/real-world-studies-for-apretude/

ViiV Healthcare shows more than 99% effectiveness in real ... ViiV HEALTHCARE SHOWS MORE THAN 99% EFFECTIVENESS IN REAL-WORLD STUDIES FOR APRETUDE (CABOTEGRAVIR LONG-ACTING), THE ONLY APPROVED LONG-ACTING ...

3. 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 ...

4. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(23)00261-8/fulltext

Efficacy and safety of long-acting cabotegravir compared ... HPTN 083 and 084 demonstrated 66% and 89% reductions in incident HIV infections for long-acting compared with daily oral PrEP in their ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301824002698

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

6. gskpro.com gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Vocabria/pdf/VOCABRIA-PI-PIL.PDF

VOCABRIA (cabotegravir) tablets, for oral use The safety and effectiveness of VOCABRIA for HIV-1 PrEP in adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition is supported by data from 2 ...

7. viivhealthcare.com viivhealthcare.com/content/dam/cf-viiv/viiv-healthcare/en_AU/documents/vocabria-pi-001-approved.pdf

VOCABRIA (cabotegravir) film-coated tablets Clinical trial data​​ The safety assessment of VOCABRIA in HIV-1-infected, virologically suppressed patients is based on pooled primary Week 48 ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36723489/

Safety and efficacy of long-acting injectable cabotegravir as ... Conclusions: CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance ...

9. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/perinatal/safety-toxicity-arv-agents-integrase-inhibitors-cabotegravir-vocabria

Appendix B: Cabotegravir - Safety and Toxicity in Pregnancy CAB-LA is FDA approved for HIV pre-exposure prophylaxis (PrEP). Human Studies in Pregnancy. Pharmacokinetics. Prospective CAB PK data during pregnancy and ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S2352301823002618

Efficacy and safety of long-acting cabotegravir compared ... Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials.