Long-acting Cabotegravir Formulations in Healthy Adults

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, Tobacco, Alcohol, others

Disqualifiers: Cardiovascular, Respiratory, Hepatic, Renal, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and metabolism of two new formulations of a medication called cabotegravir. Researchers are studying cabotegravir in healthy adults to understand its effects and how it moves through the body. Individuals who are generally healthy and have no history of major health issues, such as heart or liver disease, might be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on chronic anti-coagulation therapy (except low-dose aspirin), you may not be eligible to participate.

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

Research has shown that cabotegravir is generally safe and well-tolerated. In earlier studies, the most common side effects were mild, such as reactions at the injection site, including redness, swelling, or pain. Serious side effects were rare.

For Cabotegravir Formulation F, past trials indicated it was well-received by participants, with no major safety issues reported. Similarly, for Cabotegravir Formulation G, studies have not identified any major safety concerns. Most side effects were mild and related to the injection site.

Both formulations have undergone previous study, and while they might cause minor discomfort at the injection site, they are considered safe based on current data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cabotegravir Formulations F and G because these treatments offer a long-acting solution for HIV prevention. Unlike the standard daily oral pills, such as Truvada or Descovy, Cabotegravir is designed to be administered less frequently, potentially as infrequently as every few months. This can significantly improve adherence and convenience for users. Additionally, Cabotegravir has a different formulation that allows for extended release, which helps maintain effective drug levels in the body for a longer period, reducing the risk of missed doses and enhancing overall efficacy.

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

Research has shown that long-acting cabotegravir effectively controls the HIV virus. In large studies, about 92% of participants using cabotegravir with rilpivirine maintained very low viral levels for nearly two years. Early research also indicates that these treatments are generally safe, with injection site reactions as the most common side effect. This trial will study two formulations of long-acting cabotegravir: Formulation F and Formulation G. These findings suggest that long-acting cabotegravir could be a promising option for managing HIV. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Healthy adults over 40 kg and BMI of 18-32, not pregnant or breastfeeding, with no major health issues. Must test negative for COVID-19 on admission day, agree to use effective contraception, and have no history of drug abuse or high-risk behaviors for HIV infection.

Inclusion Criteria

Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

I was assigned female at birth, am not pregnant or breastfeeding, and meet one of the required conditions.

I tested negative for COVID-19 on the day I was admitted.

Exclusion Criteria

My blood pressure is not normal.

I have a genetic blood clotting disorder like haemophilia or VWD.

History of or on-going high-risk behaviors that, in the opinion of the investigator, may put the participant at increased risk for HIV infection including, but not limited to, participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cabotegravir Formulation F initially, followed by Cabotegravir Formulation G once available

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir Formulation F
• Cabotegravir Formulation G

Trial Overview The trial is testing two different long-acting formulations of Cabotegravir (Formulation F followed by G) in healthy participants to assess their safety, tolerability, and how the body processes them.

How Is the Trial Designed?

Group I: Part B: Participants receiving Cabotegravir Formulation G Experimental Treatment 1 Intervention

Group II: Part A: Participants receiving Cabotegravir Formulation F Experimental Treatment 1 Intervention

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

Published Research Related to This Trial

Cabotegravir (Apretude) is an effective extended-release injectable medication used as pre-exposure prophylaxis (PrEP) to significantly reduce the risk of acquiring HIV-1 in HIV-negative individuals at risk.

It is approved for use in adults and adolescents who weigh at least 35 kg (77 lb), highlighting its targeted application for those most vulnerable to sexually transmitted HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection. El-Haddad, A., Erlich, D.[2023]

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]

Cabotegravir (CAB-LA) is the first long-acting injectable medication approved for HIV preexposure prophylaxis (PrEP), showing superior efficacy compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals, as demonstrated in two phase 3 trials that were stopped early due to its effectiveness.

While CAB-LA is generally well-tolerated, with injection site reactions being the most common side effect, it may be particularly beneficial for individuals who struggle with adherence to daily oral medications, although it is more expensive than generic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis. Durham, SH., Milam, A., Waer, D., 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 (CAB LA) could significantly reduce new HIV infections in South Africa, potentially averting over 15% of new cases if administered to 10% of the adult population from 2023 to 2050.

Targeting CAB LA to high-risk groups, especially young women, would enhance its effectiveness, requiring fewer person-years of treatment to prevent each new infection compared to a broader population approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study. Smith, JA., Garnett, GP., Hallett, TB.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12339819/

Long-Term Real-World Use of Cabotegravir/Rilpivirine Despite increasing use of LA-CAB/RPV, long-term real-world data on durability, adherence, and virological outcomes remain limited to 2 years.

2. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2024/march/cabotegravir-long-acting-injectable/

Data show for the first time a new ultra long-acting ... Data show for the first time a new ultra long-acting cabotegravir formulation (CAB-ULA) that doubles the current dosing interval ...

3. thelancet.com thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00212-0/fulltext

Real-world trough concentrations and effectiveness of long ... Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12390647/

Safety, Tolerability, and Metabolic Effects of Long-Acting ... Clinical trial data suggest that LA CAB/RPV is generally safe and well tolerated. The most common side effects were injection site reactions, ...

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

Articles Effectiveness of bi-monthly long-acting injectable ... Large clinical trials have shown the long-term effectiveness of injectable cabotegravir in combination with rilpivirine as maintenance treatment for HIV in well ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/215499s000lbl.pdf

APRETUDE (cabotegravir) Label - accessdata.fda.gov The safety assessment of APRETUDE is based on the analysis of data from 2 international, multicenter, double-blind trials, HPTN 083 and HPTN 084 [see Clinical ...

7. 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 ...

8. lgcstandards.com lgcstandards.com/medias/sys_master/root/h3e/h54/11013849481246/SDS_TRC-C050100-100MG_ST-WB-MSDS-5498337-1-1-1/SDS-TRC-C050100-100MG-ST-WB-MSDS-5498337-1-1-1.PDF

SAFETY DATA SHEET Causes skin irritation. Serious eye damage/eye irritation Classification based on data available for ingredients. Causes serious eye irritation. Respiratory or ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06033547

NCT06033547 | A Study to Investigate the ... The primary purpose of the study is to investigate the safety, tolerability, and pharmacokinetic (PK) profiles of two different cabotegravir formulations in ...