A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE

Study Overview
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Brief Summary
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This is a Phase 3,multicenter, randomized, open-label, blinded endpoint evaluation study comparing the effect of abelacimab relative to apixaban on venous thromboembolism (VTE) recurrence and bleeding in patients with cancer associated VTE (ASTER)

Detailed Description
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Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. The two most common treatments today are low molecular weight heparin (LMWH) and direct anticoagulants (DOACs), in which each has limitations. DOACs are administered orally and are seen as a more convenient alternative though associated with bleeding risk; further, some cancer patients have difficulty swallowing or develop vomiting which leads to unpredictable pharmacodynamic effects with oral therapy. The ANT-007 study will compare treatment with abelacimab monthly administration to apixaban twice daily administration over a 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months

Official Title
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A Multicenter, Randomized, Open-label, Blinded Endpoint Evaluation, Phase 3 Study Comparing the Effect of Abelacimab Relative to Apixaban on Venous Thromboembolism (VTE) Recurrence and Bleeding in Patients With Cancer Associated VTE

Conditions
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Venous Thromboembolism, Deep Venous Thrombosis, Pulmonary Embolism

Intervention / Treatment
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* Biological: Abelacimab
* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥18 years old or other legal maturity age according to the country of residence Confirmed diagnosis of cancer (by histology, adequate imaging modality), other than basal-cell or squamous-cell carcinoma of the skin alone with one of the following: Active cancer, defined as either locally active, regionally invasive, or metastatic cancer at the time of randomization and/or Currently receiving or having received anticancer therapy (radiotherapy, chemotherapy, hormonal therapy, any kind of targeted therapy or any other anticancer therapy) in the last 6 months. Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) (i.e., popliteal, femoral, iliac, and/or inferior vena cava [IVC] thrombosis) and/or a confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 120 hours from diagnosis of the qualifying VTE Anticoagulation therapy with a therapeutic dose of DOAC for at least 6 months is indicated Able to provide written informed consent Exclusion Criteria: Thrombectomy, insertion of a caval filter or use of a fibrinolytic agent to treat the current (index) DVT and/or PE More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, fondaparinux, DOAC, or other anticoagulants An indication to continue treatment with therapeutic doses of an anticoagulant other than that VTE treatment prior to randomization (e.g., atrial fibrillation [AF], mechanical heart valve, prior VTE) Platelet count <50,000/mm3 at the screening visit PE leading to hemodynamic instability (blood pressure [BP] <90 mmHg or shock) Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within the 4 weeks preceding screening Brain trauma or a cerebral or spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening Need for aspirin in a dosage of >100 mg/day or any other antiplatelet agent alone or in combination with aspirin Primary brain cancer or untreated intracranial metastases at baseline Acute myeloid or lymphoid leukemia Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening Life expectancy <3 months at randomization Calculated creatinine clearance (CrCl) <30 mL/min (Cockcroft-Gault equation) at the screening visit Hemoglobin <8 g/dL at the screening visit Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase (ALT) ≥3 x and/or bilirubin ≥2 x upper limit of normal (ULN) at the screening visit in absence of clinical explanation Uncontrolled hypertension (systolic BP>180 mm Hg or diastolic BP >100 mm Hg despite antihypertensive treatment) Women of child-bearing potential (WOCBP) who are unwilling or unable to use highly effective contraceptive measures during the study from screening up to 3 days after last treatment of apixaban or 100 days after administration of abelacimab (See Section 5.3.6. for highly effective contraceptive measures) Sexually active males with sexual partners of childbearing potential must agree to use a condom or other reliable contraceptive measure up to 3 days after last treatment of apixaban or 100 days after administration of abelacimab Pregnant or breast-feeding women Patients known to be receiving strong dual inducers or inhibitors of both CYP3A4 and P gp History of hypersensitivity to any of the study drugs (including apixaban) or excipients, to drugs of similar chemical classes, or any contraindication listed in the label for apixaban Subjects with any condition that in the Investigator's judgement would place the subject at increased risk of harm if he/she participated in the study Use of other investigational (not registered) drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic(s) (PD) effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abelacimab<br>Abelacimab intravenous administration followed by monthly administration of the same dose subcutaneously | Biological: Abelacimab<br>* Abelacimab 150 mg<br>* Other names: MAA868;|
| Active Comparator: Apixaban<br>Apixaban administered orally twice a day | Drug: Apixaban<br>* Apixaban 10 mg followed by 5 mg<br>* Other names: Eliquis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first event of centrally adjudicated VTE recurrence consisting of new proximal deep venous thrombosis, new pulmonary embolism (PE) or fatal PE, including unexplained death for which PE cannot be ruled out |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first event of ISTH-adjudicated major or clinically relevant non-major (CRNM) bleeding events |  | 6 months | 
| Net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticoagulants, VTE recurrence rate, PROBE design, LMWH, CAT, Cancer associated VTE, Abelacimab, Apixaban, FXI, Major bleeding events, CRNM bleeding events