Phase 3 Multicenter Randomized Study of Abelacimab vs. Apixaban on VTE Recurrence and Bleeding in Cancer-Associated Venous Thromboembolism

The primary objective of this study is to evaluate whether **abelacimab** is non-inferior to **apixaban** in preventing the recurrence of **venous thromboembolism (VTE)** at six months post-randomization in patients with cancer-associated VTE. This assessment is clinically significant as it aims to determine if abelacimab can provide a comparable level of efficacy to apixaban, a standard treatment, in reducing VTE recurrence, which is a critical concern in cancer patients due to their increased risk of thrombotic events. If non-inferiority is established, the study will further assess the potential superiority of abelacimab over apixaban.

The clinical trial involves a total of **356 participants** diagnosed with **venous thromboembolism (VTE)**, specifically targeting individuals with cancer and recently diagnosed VTE. The study population includes both male and female subjects aged 18 years and older, encompassing a vulnerable population due to the inclusion of cancer patients. Participants were selected based on their confirmed diagnosis of cancer, excluding basal-cell or squamous-cell carcinoma of the skin alone, and must have active cancer or have received anticancer therapy within the last six months. The trial also requires participants to have a confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) or pulmonary embolism (PE) and to be eligible for anticoagulation therapy with a therapeutic dose of direct oral anticoagulants (DOAC) for at least six months. The ability to provide written informed consent is mandatory for participation. The trial does not specify particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **randomized**, open-label, blinded endpoint evaluation, phase 3 study designed to compare the effect of **abelacimab** relative to **apixaban** on the recurrence of **venous thromboembolism (VTE)** and bleeding in patients with cancer-associated VTE. The primary objective is to assess whether abelacimab is non-inferior to apixaban for preventing VTE recurrence at six months post-randomization. If non-inferiority is demonstrated, the study will further assess for superiority. The trial is expected to conclude by September 2025, with recruitment having commenced in December 2021.

Participants will be involved in the study for a maximum of six months, during which they will undergo a series of study visits. The sequence of visits includes an initial screening visit to confirm eligibility based on criteria such as age, cancer diagnosis, and recent VTE diagnosis. Following randomization, participants will receive either abelacimab via **subcutaneous use** or apixaban in the form of **film-coated tablets** for oral use. Regular follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will occur at the six-month mark, where the primary endpoint, time to first event of centrally adjudicated VTE recurrence, will be evaluated.

Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or withdraw consent. The trial's design ensures that all data collected will contribute to understanding the comparative efficacy and safety of abelacimab and apixaban in this patient population. The study's findings will be critical in guiding future therapeutic strategies for managing VTE in cancer patients.

The clinical trial involves the administration of **Abelacimab**, a **concentrate for solution for infusion**. Abelacimab is provided at a concentration of 150 mg/ml and is administered via **subcutaneous use**. The maximum daily dose is 150 mg, with a total treatment period of up to 6 months. Abelacimab is a protein-based therapeutic agent developed by Anthos Therapeutics Inc. It is not a paediatric formulation and is classified as a medicinal product of biological origin. The administration schedule and participant compliance are monitored throughout the study to ensure adherence to the dosing regimen.

The comparator treatment in this study is **Eliquis**, which contains the active substance **Apixaban**. Eliquis is available in the form of **film-coated tablets**, each containing 5 mg of Apixaban. The tablets are administered orally, with a maximum daily dose of 10 mg. The treatment duration is also set for a period of 6 months. Apixaban is a chemically synthesized compound, and the product is manufactured by Bristol-Myers Squibb/Pfizer EEIG. As with Abelacimab, participant compliance with the dosing schedule is closely monitored to ensure the integrity of the trial results.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the time to the first event of centrally adjudicated **venous thromboembolism (VTE)** recurrence through 6 months. This endpoint will be measured to determine whether abelacimab is non-inferior to apixaban in preventing VTE recurrence in patients with cancer-associated VTE. If non-inferiority is demonstrated, the trial will further assess the superiority of abelacimab over apixaban. The trial is designed as a multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study. The primary objective is to assess the efficacy of abelacimab relative to apixaban over a 6-month period post-randomization. The study will involve patients with a confirmed diagnosis of cancer and recently diagnosed VTE, who meet the inclusion criteria and have provided written informed consent. The efficacy assessments will be conducted through a centrally adjudicated process to ensure the accuracy and reliability of the results.