Detailed Description:
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
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
Primary outcome:
1. 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 (Time Frame - 6 months)
Secondary outcome:
1. Time to first event of ISTH-adjudicated major or clinically relevant non-major (CRNM) bleeding events (Time Frame - 6 months)
2. Net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding (Time Frame - 6 months)
- Experimental: Abelacimab
Abelacimab intravenous administration followed by monthly administration of the same dose subcutaneously - Active Comparator: Apixaban
Apixaban administered orally twice a day
- Abelacimab (MAA868):
Abelacimab 150 mg - Apixaban (Eliquis):
Apixaban 10 mg followed by 5 mg
Quelle: ClinicalTrials.gov
