IRB Study Number 22-815
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
• To assess whether abelacimab is non-inferior to apixaban for preventing VTE recurrence through 6 months post randomization in patients with cancer and recently diagnosed VTE
Secondary Objectives
• To assess whether abelacimab is superior to apixaban for preventing occurrence of the composite of major or CRNM bleeding through 6 months post randomization.
• To assess whether abelacimab is superior to apixaban on net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding events through 6 months post randomization.
• To assess whether abelacimab is superior to apixaban for preventing VTE recurrence at 6 months post randomization.
• To assess whether abelacimab is superior to apixaban on the rate of permanent treatment discontinuation not due to death through 6 months post randomization.
• To assess whether abelacimab is superior to apixaban for preventing occurrence of CRNM bleeding events through 6 months post randomization.
• To assess whether abelacimab is superior to apixaban for preventing occurrence of major bleeding events through 6 months post randomization.
• To assess whether abelacimab is superior to apixaban for preventing occurrence of the composite of GI major and GI CRNM bleeding through 6 months post randomization.
• To evaluate safety and tolerability of abelacimab relative to dalteparin through 6 months post randomization and to assess incidence rate of injection site reactions, hypersensitivity reactions and immunogenicity in patients treated with abelacimab.
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 basalcell or squamous-cell carcinoma of the skin alone with one of the following:
o Active cancer, defined as either locally active, regionally invasive, or metastatic cancer at the time of randomization and/or
o 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 acute DVT (i.e., popliteal, femoral, iliac, and/or inferior vena cava [IVC] thrombosis) and/or a confirmed symptomatic PE, or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 72 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 72 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., AF, mechanical heart valve, prior VTE)
• Platelet count <50,000/mm3
• 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 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 major surgery at baseline
• 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)
• Hemoglobin <8 g/dL
• Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase (ALT) ≥3 x and/or bilirubin ≥2 x upper limit of normal (ULN) 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 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.
