E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
venous thromboembolism (VTE) |
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E.1.1.1 | Medical condition in easily understood language |
blood clot in leg veins and/or in the pulmonary artery in the lungs |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess whether abelacimab is non-inferior to apixaban for preventing VTE recurrence at 6 months post randomization in patients with cancer and recently diagnosed VTE. If non-inferiority is demonstrated, then superiority will be assessed. |
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E.2.2 | Secondary objectives of the trial |
•To assess whether abelacimab is superior to apixaban for preventing occurrence of the composite of major or CRNM bleeding •To assess whether abelacimab is superior to apixaban on net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding events •To assess whether abelacimab is superior to apixaban on the rate of permanent treatment discontinuation not due to death •To assess whether abelacimab is superior to apixaban for preventing occurrence of CRNM bleeding events •To assess whether abelacimab is superior to apixaban for preventing occurrence of major bleeding events •To assess whether abelacimab is superior to apixaban for preventing the occurrence of the composite of GI major and GI CRNM bleeding •To evaluate safety and tolerability of abelacimab relative to apixaban and to assess incidence rate of injection site reactions, hypersensitivity reactions and immunogenicity in patients treated with abelacimab
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenomic study requiring samples to be collected at Day 1 (DNA). |
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E.3 | Principal inclusion criteria |
•Male or female subjects ≥18 years old or another legal maturity age according to the country of residence •Confirmed diagnosis of cancer (by histology or adequate imaging modality), other than basal-cell or squamous-cell carcinoma of the skin alone with one of the following: oActive cancer, defined as either locally active, regionally invasive, or metastatic cancer at the time of randomization, and/or oCurrently 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 DVT (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic or incidental PE of a segmental, or larger pulmonary artery, and/or a confirmed symptomatic or incidental PE of two or more subsegmental pulmonary arteries. 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.
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E.4 | Principal exclusion criteria |
•Thrombectomy, insertion of a caval filter or use of a fibrinolytic agent to treat the current (index) occurrence of 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 used for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical heart valve, prior VTE) •Platelet count <50,000/mm3 at the screening visit •PE leading to hemodynamic instability (systolic blood pressure [BP] <90 mmHg or shock) •Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within 4 weeks preceding screening •Brain trauma, or a cerebral or a spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia or a spinal cord surgery in the 4 weeks preceding screening •Need for aspirin in a dosage of more than 100 mg/per 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 at baseline •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 less than 8 g/dL at the screening visit •Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and/or bilirubin level 2 times or more higher the upper limit of the normal range 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 dalteparin 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 dalteparin 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 its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for apixaban •Subjects with any condition that as judged by the Investigator 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 effect has returned to baseline, whichever is longer. Participation in academic non-interventional or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first event of centrally adjudicated VTE recurrence through 6 months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months post randomization |
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E.5.2 | Secondary end point(s) |
1. Time to first event of ISTH-adjudicated major or CRNM bleeding events through 6 months 2. Time to first event of VTE recurrence, ISTH adjudicated major or ISTH-adjudicated CRNM bleeding events through 6 months 3. Time to event of permanent treatment discontinuation not due to death 4. Time to first event of ISTH-adjudicated CRNM bleeding events through 6 months 5. Time to first event of ISTH-adjudicated major bleeding events through 6 months 6. Time to first event of GI ISTH-adjudicated major and CRNM bleeding events through 6 months 7. All-cause death, vascular death, serious adverse events, adverse events leading to drug discontinuation, other adverse events, abnormal lab tests, etc. presented as rate per 100 patient years • For patients treated with abelacimab: o Percentage of patients with injection site reactions o Percentage of patients with injection site reactions by severity status o Percentage of patients with hypersensitivity reactions o Percentage of patients with hypersensitivity reactions by severity status o Percentage of patients with ADA formation o Percentage of patients with persistent ADA formation o Percentage of patients with neutralizing antibody (NAb) formation. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months post randomization |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Switzerland |
Taiwan |
Australia |
Canada |
China |
Japan |
Korea, Republic of |
United Kingdom |
United States |
Austria |
Czechia |
France |
Germany |
Hungary |
Ireland |
Italy |
Latvia |
Netherlands |
Norway |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |