venous thromboembolism
Conditions
Interventions
• Abelacimab 150 mg iv on Day 1 then, starting approximately 30 days later,
abelacimab 150 mg sc every month for an additional 5 months
(sc administration planned on Days 31, 61, 91, 121, and 151 ±5
Sponsors
Anthos Therapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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: o Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and o No intended curative surgery during the study • Confirmed symptomatic or incidental proximal lower limb acute DVT (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein 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 LMWH for at least 6 months is indicated. • Able to provide written informed consent
Exclusion criteria
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, or other anticoagulants • An indication to continue treatment with therapeutic doses of an anticoagulant other than that for VTE treatment prior to randomization (e.g., AF, mechanical heart valve, prior VTE) • PE leading to hemodynamic instability (blood pressure [BP] <90 mmHg or shock) • Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within 4 weeks of 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 • Bleeding requiring medical attention at the time of randomization or within the preceding 4 weeks • Planned major surgery at baseline • History of heparin-induced thrombocytopenia • Primary brain cancer or untreated intracranial metastasis • 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) • Platelet count <50,000/mm3 • 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 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 • 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 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 testing different strategies or different combinations of registered drugs is permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is to assess whether abelacimab is non-inferior to dalteparin for preventing VTE recurrence through 6 months post randomization in patients with GI or GU cancer and recently diagnosed VTE. If non-inferiority is demonstrated, then superiority will be assessed. | — |
Secondary
| Measure | Time frame |
|---|---|
| o To assess whether abelacimab is superior to dalteparin for preventing occurrence of the composite of major or CRNM bleeding through 6 months post-randomization o To assess whether abelacimab is superior to dalteparin on net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding events through 6 months post-randomization o To assess whether abelacimab is superior to dalteparin on the rate of permanent treatment discontinuation not due to death through 6 months post-randomization o To assess whether abelacimab is superior to dalteparin for preventing occurrence of CRNM bleeding events through 6 months post randomization o To assess whether abelacimab is superior to dalteparin for preventing occurrence of major bleeding events through 6 months postrandomization o To assess whether abelacimab is superior to dalteparin for preventing occurrence of the composite of GI major and CRNM bleeding through 6 months post-randomization o To evaluate safety and tolerability of abelacimab relative to dalteparin through 6 months post randomization and to assess the incidence rate of injection site reactions, hypersensitivity reactions and immunogenicity in patients treated with abelacimab | — |
Countries
Netherlands
Outcome results
None listed