CAB ULA for HIV Infection
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: ViiV Healthcare
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.
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.
12345Is 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.
79101112What 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.
6781112Will 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.
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
I am 18 years or older and weigh at least 35 kg.
Exclusion Criteria
I have skin conditions that could affect injection safety.
I need long-term blood thinners.
I haven't had any cancer except skin cancer in the last 5 years.
I have not been exposed to more than 4 new drugs in the last year.
I haven't had significant seizures in the last 2 years.
I am infected with HIV.
I am not allergic to the medications used in this study.
I do not have implants or skin conditions at the injection site.
I am showing signs of a recent HIV infection.
I have tested positive for hepatitis B.
I have lost more than 500 mL of blood in the last 56 days.
I have used CAB LA for HIV prevention in the last year.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: CAB GroupExperimental Treatment2 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
GSK Investigational SiteOakbrook, IL
GSK Investigational SiteMobile, AL
GSK Investigational SiteCoral Gables, FL
GSK Investigational SiteOak Brook, IL
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Who is running the clinical trial?
ViiV HealthcareLead Sponsor
References
Preoperative UFT and calcium folinate and radiotherapy in rectal cancer. [2013]Protracted infusions of 5-fluorouracil (5-FU) combined with pelvic radiotherapy have been associated with improved survival and decreased local and distant metastases in the adjuvant therapy of rectal cancer. However, this method of 5-FU infusion requires the inconvenience and expense of central venous line placement and care, infusion pumps, and treatment of catheter-related complications. We previously demonstrated that a completely oral therapy with UFT (uracil plus tegafur in a 4:1 molar ratio) plus oral calcium folinate (Orzel) can achieve pharmacokinetic parameters similar to those associated with protracted 5-FU infusions. This trial examines the feasibility of using UFT plus oral calcium folinate both during preoperative pelvic radiation and postoperatively, and shows that patients can be treated safely and effectively with a completely oral chemotherapy program combining UFT plus oral calcium folinate with pelvic radiation therapy.
Oral tegafur/uracil. [2018]Tegafur is a prodrug of the antineoplastic agent fluorouracil, and is administered in a 1:4 molar ratio with the fluorouracil modulator uracil. Oral tegafur/uracil 300 mg/m(2)/day plus calcium folinate 75 or 90 mg/day for 28 days every 35 days was as effective as intravenous (IV) fluorouracil 425 mg/m(2)/day plus folinic acid 20 mg/m(2)/day for 5 days every 28 or 35 days in the treatment of patients with metastatic colorectal cancer in two large, randomised, nonblind, multicentre trials (n = 816 and 380). Median survival time among patients treated with tegafur/ uracil or fluorouracil was approximately 12 months in both trials. Results from both trials also demonstrated no significant between-group differences in overall response rates among patients treated with oral tegafur/uracil (12 and 11%) or IV fluorouracil (15 and 9%). In elderly patients (aged > or = 70 years) with metastatic colorectal cancer, results from small noncomparative studies showed that treatment with oral tegafur/uracil afforded overall response rates of 12.5 to 29% and was well tolerated. During preoperative treatment with oral tegafur/uracil plus calcium folinate as an adjunct to radiotherapy in patients with stage II or III rectal cancer, the maximum tolerated dosage of tegafur/uracil was 350 mg/m(2)/day (administered 5 days per week for 5 weeks). Among the 15 patients who were followed for 5 to 8 months, three had a complete response to treatment. Treatment with tegafur/uracil was also given postoperatively. The most common adverse events associated with oral tegafur/uracil were anaemia, nausea/vomiting, diarrhoea, thrombocytopenia, mucositis, neutropenia, asthenia, anorexia and abdominal pain. Oral tegafur/uracil was associated with a significantly more favourable tolerability profile than IV fluorouracil in the two large randomised trials. In particular, stomatitis and most adverse haematological events were less frequent.
[Multicenter phase II clinical trial of uroacitides injection in the treatment for advanced malignant tumors]. [2008]To investigate the efficacy, safety and the life quality improvement of uroacitides injection in the treatment for patients with advanced malignant tumors.
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]The purpose of this study was to evaluate the efficacy of tegafur-uracil (UFT) administration as a fourth-line therapy in patients with castration-resistant prostate cancer (CRPC) who had already received combined androgen blockade (CAB) therapy (first-line), alternative antiandrogen therapy (second-line), and estramustine phosphate sodium hydrate (EMP) therapy (third-line), in order to determine who would benefit from UFT therapy.
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]We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported.
Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1. [2020]Human Immunodeficiency Virus (HIV) is a chronic infection that depletes the immune system of essential components causing those infected to be at risk for multiple life-threatening infections. Worldwide, millions live with this infection, the vast majority attributable to HIV-1. Transmission persists with hundreds of thousands of new infections reported yearly. Implementation of combination antiretroviral therapy (cART) has been effective in improving outcomes and decreasing transmission. Newer co-formulated agents have provided simpler medication regimens, fewer side effects, and, in some cases, a higher barrier to the emergence of medication resistance. Areas covered: Here, we review trials of cabotegravir (CAB) as treatment of HIV-1 infection and its potential use as pre-exposure prophylaxis (PrEP) in high risk individuals, including issues around oral lead in and potential resistance emergence. Expert opinion: CAB is efficacious when used in combination therapy orally or given intramuscularly every 4 to 8 weeks. Its availability in a long-acting injectable formulation (CAB-LA) makes it a valuable, novel drug to treat HIV-1 infection when combined with long-acting injectable rilpivirine (RPV-LA). Moreover, pre-clinical and early Phase 2a studies support its testing as monotherapy as PrEP. Studies are underway comparing the efficacy of every 8 week CAB-LA to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC).
Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. [2023]Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States.
Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. [2022]Cabotegravir/rilpivirine (CAB/RPV) was recently approved by the US Food and Drug Administration (FDA) as the first complete parenteral antiretroviral (ART) regimen for treatment of people living with HIV (PLWH). As a monthly intramuscular (IM) injection, this therapy constitutes a major departure from the traditional paradigm of oral therapy requiring (at least) daily administration that has defined HIV treatment for decades. Composed of a second-generation integrase inhibitor (INSTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI), CAB/RPV has achieved high rates of sustained virologic suppression with a favorable safety profile for treatment-experienced PLWH following oral lead-in (OLI) during several clinical trials. In addition to the clinical benefits of this agent, patient-reported outcomes associated with convenience, confidentiality, and the tolerability of the injections have consistently reflected positive perceptions of CAB/RPV. The novel nature of this therapy in the field of HIV presents logistical challenges. Clinics will need to address barriers related to management of clinic workflow, procurement, reimbursement, and nonadherence. The aim of this review was to summarize the available safety, efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) data of this long-acting (LA) injectable regimen as well as discuss some potential considerations for prescribing and operationalization.
Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis. [2023]Review the pharmacology, pharmacokinetics, efficacy, safety, and role of long-acting injectable cabotegravir (CAB-LA) in HIV preexposure prophylaxis (PrEP).
The Long-Acting Cabotegravir Tail as an Implementation Challenge: Planning for Safe Discontinuation. [2023]The long-acting feature of cabotegravir, an integrase-inhibitor highly effective in preventing acquisition of HIV in adolescents and adults, is both its greatest strength and a challenge to its implementation. Cab-LA is administered at 8-week intervals (after an initial loading dose) but has a long, variable drug "tail" that may leave users vulnerable to future drug resistance if they contract HIV during this critical period. The potential for cab-LA to meaningfully contribute to ending the HIV Epidemic is hindered by, among other factors, limited resources to guide patients and providers on how to safely discontinue injections. We suggest three key strategies to overcome this specific challenge: (1) Comprehensive patient education and counseling about the drug tail; (2) Training and coaching PrEP care teams, including clinical and non-clinical staff, on communication around the tail; (3) Adherence support strategies, including monitoring of cabotegravir drug levels after discontinuation, for a personalized medicine approach to safe discontinuation.
Long-acting injectable cabotegravir for PrEP: A game-changer in HIV prevention? [2023]Long-acting injectable cabotegravir (CAB-LA) represents a new additional option for HIV prevention in people at substantial risk of HIV infection that may fill the gaps in pre-exposure prophylaxis (PrEP) uptake, adherence, and retention in users having difficulty with oral PrEP. Data from clinical trials demonstrated that CAB-LA was safe, highly effective, and well-accepted for HIV prevention. However, the occurrence of breakthrough HIV infections despite timely injections, HIV seroconversion timing and patterns, risk of selection and dissemination of resistance-associated mutations to integrase inhibitors, complexity of follow-up, logistical considerations, and its cost effectiveness compared with oral PrEP constitute significant issues for the integration of CAB-LA into clinical routine.
Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. [2023]The first complete long-acting antiretroviral therapy (ART) regimen, cabotegravir + rilpivirine long-acting (CAB + RPV LA) injectable, was approved in the US for HIV-1 treatment in individuals on a stable antiretroviral regimen with a viral load