CAB ULA for HIV Infection

Recruiting at 3 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: ViiV Healthcare

Must not be taking: Anti-coagulants

Disqualifiers: Cardiovascular, Respiratory, HIV, Hepatitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study will assess the pharmacokinetics (PK), safety, and tolerability of CAB ULA administered every 4 months (Q4M) following administration of CAB LA every 2 months (Q2M), in healthy adult volunteers.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on any protocol-prohibited medications or if you need chronic anti-coagulants.

What data supports the effectiveness of the drug CAB ULA for HIV infection?

Research shows that cabotegravir, when used as a long-acting injectable (CAB LA), is safe and effective for HIV prevention and treatment. It has been shown to maintain viral suppression in people living with HIV and is well-accepted for use as pre-exposure prophylaxis (PrEP) in high-risk individuals. ^{1 2 3 4 5}

Is Cabotegravir Ultra Long-acting (CAB ULA) safe for humans?

Cabotegravir, in its long-acting form, has been shown to be safe and well-tolerated in clinical trials for HIV prevention and treatment. It is used as an injectable option for people at risk of HIV, and while it is generally safe, there are some challenges related to its long-lasting effects and potential for drug resistance if not managed properly. ^{1 3 5 6 7}

What makes the drug Cabotegravir Ultra Long-acting (CAB ULA) unique for treating HIV?

Cabotegravir Ultra Long-acting (CAB ULA) is unique because it is designed to be a long-acting injectable treatment, potentially reducing the frequency of dosing compared to daily oral medications, which can improve adherence and convenience for patients with HIV. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for healthy adults who may be at risk of HIV infection. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study or pose a risk.

Inclusion Criteria

Healthcare staff able to understand and comply with protocol requirements

Participants who are overtly healthy as determined by medical evaluation

I am not able to become pregnant or am using birth control.

Exclusion Criteria

I have skin conditions that could affect injection safety.

I need long-term blood thinners.

I have not been exposed to more than 4 new drugs in the last year.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

CAB LA Phase

Participants receive the CAB LA Q2M regimen

9 months

CAB ULA Phase

Participants receive the CAB ULA Q4M regimen

14 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Treatment Details

Interventions

• Cabotegravir Long-acting (CAB LA) (Antiretroviral Agent)
• Cabotegravir Ultra Long-acting (CAB ULA) (Antiretroviral Agent)

Trial Overview The study is testing two forms of Cabotegravir: an ultra long-acting version (CAB ULA) given every four months versus a long-acting version (CAB LA) administered every two months, to compare their levels in the body, safety, and how well they are tolerated.

Participant Groups

Group I: CAB Group Experimental Treatment 2 Interventions

Participants will receive the CAB LA Q2M regimen up to Month 9 then will receive the CAB ULA Q4M regimen up to Month 23.

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

Findings from Research

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/rilpivirine (CAB/RPV) is the first complete injectable antiretroviral therapy approved for HIV treatment, offering a monthly intramuscular injection option that improves adherence compared to daily oral medications.

Clinical trials have shown CAB/RPV to achieve high rates of sustained viral suppression with a favorable safety profile, while also enhancing patient satisfaction due to its convenience and confidentiality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. Howe, ZW., Norman, S., Lueken, AF., et al.[2022]

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) is an effective treatment for HIV-1 infection, showing efficacy both as part of combination therapy and as a long-acting injectable formulation administered every 4 to 8 weeks.

CAB is also being explored as a pre-exposure prophylaxis (PrEP) for high-risk individuals, with ongoing studies comparing its effectiveness to standard PrEP regimens, indicating its potential to reduce new infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1. McPherson, TD., Sobieszczyk, ME., Markowitz, M.[2020]

Long-acting injectable cabotegravir (CAB-LA) is a promising new option for HIV prevention, showing high safety and efficacy in clinical trials, particularly for individuals struggling with adherence to oral PrEP.

Despite its potential, challenges such as breakthrough infections, logistical issues, and the need for comprehensive implementation strategies must be addressed to fully integrate CAB-LA into HIV prevention programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention? Liegeon, G., Ghosn, J.[2023]

Cabotegravir is a long-acting integrase-inhibitor that effectively prevents HIV acquisition in adolescents and adults, administered every 8 weeks, but poses a risk of drug resistance due to its long 'tail' if HIV is contracted during this period.

To safely manage the discontinuation of cabotegravir injections, it is crucial to implement comprehensive patient education, train healthcare teams on communication regarding the drug tail, and provide adherence support strategies, including monitoring drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long-Acting Cabotegravir Tail as an Implementation Challenge: Planning for Safe Discontinuation. Meyers, K., Nguyen, N., Zucker, JE., 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]

A trial demonstrated that using an oral chemotherapy regimen of UFT (uracil plus tegafur) combined with oral calcium folinate is a feasible and effective alternative to protracted infusions of 5-fluorouracil (5-FU) during pelvic radiotherapy for rectal cancer.

This oral treatment approach allows for safe administration without the need for central venous lines or infusion pumps, potentially reducing complications and improving patient convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative UFT and calcium folinate and radiotherapy in rectal cancer. Hoff, PM., Lassere, Y., Pazdur, R., et al.[2013]

In a study of 26 patients with castration-resistant prostate cancer (CRPC), tegafur-uracil (UFT) as a fourth-line therapy showed a 46.2% response rate in reducing prostate-specific antigen (PSA) levels, indicating its potential efficacy in this advanced stage of cancer.

UFT was well-tolerated, with only 7.7% of patients experiencing significant side effects, suggesting it can be safely administered even to older patients (over 75 years) without compromising their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tegafur-uracil (UFT) administration in castration-resistant prostate cancer patients with a history of both alternative antiandrogen therapy and estramustine phosphate sodium hydrate therapy. Hayakawa, N., Matsumoto, K., Sato, A., et al.[2021]

The modified UFT/LV treatment combined with bevacizumab showed a median progression-free survival of 8.2 months and an overall survival of 23 months in elderly patients (≥ 75 years) with metastatic colorectal cancer, indicating its efficacy in this population.

The treatment was well-tolerated, with the most common severe side effects being hypertension (12%) and fatigue (8%), suggesting that it is a safe option for older patients, despite two treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study). Nishina, T., Moriwaki, T., Shimada, M., et al.[2022]

Oral tegafur/uracil combined with calcium folinate was found to be as effective as intravenous fluorouracil in treating metastatic colorectal cancer, with both treatments resulting in a median survival time of approximately 12 months across two large trials involving 1,196 patients.

Tegafur/uracil demonstrated a more favorable tolerability profile compared to intravenous fluorouracil, with fewer adverse events such as stomatitis and hematological issues, making it a potentially safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral tegafur/uracil. Wellington, K., Goa, KL.[2018]

In a phase II clinical trial involving 160 patients with advanced cancers, uroacitides injection demonstrated a tumor control rate of 65.2% and a clinical benefit response rate of 57.2%, indicating its efficacy in managing various types of advanced malignancies.

The treatment was associated with mild and reversible side effects, such as nausea and pain, suggesting that uroacitides injection is a tolerable option for improving the quality of life in patients with advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multicenter phase II clinical trial of uroacitides injection in the treatment for advanced malignant tumors]. Li, Q., Feng, FY., Chen, Q., et al.[2008]

References

1. 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]

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

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. [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. England pubmed.ncbi.nlm.nih.gov

Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1. [2020]

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

Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention? [2023]

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

The Long-Acting Cabotegravir Tail as an Implementation Challenge: Planning for Safe Discontinuation. [2023]

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

Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis. [2023]

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

Preoperative UFT and calcium folinate and radiotherapy in rectal cancer. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of tegafur-uracil (UFT) administration in castration-resistant prostate cancer patients with a history of both alternative antiandrogen therapy and estramustine phosphate sodium hydrate therapy. [2021]

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

Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study). [2022]

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

Oral tegafur/uracil. [2018]

12. China pubmed.ncbi.nlm.nih.gov

[Multicenter phase II clinical trial of uroacitides injection in the treatment for advanced malignant tumors]. [2008]