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.
Patients with intact GI and GU cancer have increased bleeding risk with oral direct
anticoagulants (DOACs), Guidelines advice caution with those DOACs or state preference for
low molecular weight heparin (LMWH) in this population. The ANT-008 study will compare
treatment with abelacimab monthly administration to LMWH daily subcutaneous (sc)
administration over 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 GI (colorectal, pancreatic, gastric, esophageal, gastro-esophageal junction
or hepatobiliary) or confirmed GU (renal, ureteral, bladder, prostate, or urethra)
cancers if:
- Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and
- No intended curative surgery during the study
- Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT)
(i.e., popliteal, femoral, iliac, and/or inferior vena cava vein 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 LMWH 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) occurrence of DVT and/or PE
- More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, or other
anticoagulants
- An indication to continue treatment with therapeutic doses of an anticoagulant other
than for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical
heart valve, prior VTE)
- PE leading to hemodynamic instability (systolic BP <90 mmHg or shock).
- Acute ischemic or hemorrhagic stroke or intracranial hemorrhage, in the last 4 weeks
preceding screening.
- Brain trauma, or cerebral or a 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 more than 100 mg/day or, any other antiplatelet agent
alone or in combination with aspirin
- 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
- History of heparin induced thrombocytopenia
- Infective acute or subacute endocarditis at the time of presentation
- Primary brain cancer or untreated intracranial metastasis
- Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
- Life expectancy of <3 months at randomization
- Calculated creatinine clearance (CrCl) <30 mL/min at the screening visit
- Platelet count <50,000/ mm3 at the screening visit
- Hemoglobin <8 g/dL at the screening visit
- Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine
aminotransferase ≥3 times and/or bilirubin ≥2 times the upper limit of normal (ULN) at
the screening visit in the absence of clinical explanation
- Uncontrolled hypertension (systolic blood pressure [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
- 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
- History of hypersensitivity to any of the study drugs (including dalteparin) or its
excipients, to drugs of similar chemical classes, or any contraindication listed in
the label for dalteparin
- Subjects with any condition that in the judgement of 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 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: Dalteparin
Dalteparin administered subcutaneously daily
- Abelacimab (MAA868):
Abelacimab 150 mg - Dalteparin (Fragmin):
Dalteparin 200 IU/kg/day followed by 150 IU/kg/day
Quelle: ClinicalTrials.gov
