MAGNOLIA: A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE

Sponsor

Anthos Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05171075

Collaborator

Itreas (Other)

1,020

Enrollment

Location

Arms

22.1

Anticipated Duration (Months)

46.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 3, multicenter, open-label, blinded endpoint study to evaluate the effect of abelacimab relative to dalteparin on venous thromboembolism (VTE) recurrence and bleeding in patients with gastrointestinal (GI)/genitourinary (GU) cancer associated VTE (Magnolia)

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism Deep Venous Thrombosis Pulmonary Embolism	Biological: Abelacimab Drug: Dalteparin	Phase 3

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1020 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Open-label, Blinded Endpoint Evaluation, Phase 3 Study Comparing the Effect of Abelacimab vs. Dalteparin on Venous Thromboembolism (VTE) Recurrence and Bleeding in Patients With GI/GU Associated VTE

Anticipated Study Start Date :

Jul 29, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abelacimab Abelacimab intravenous administration followed by monthly administration of the same dose subcutaneously	Biological: Abelacimab Abelacimab 150 mg Other Names: MAA868
Active Comparator: Dalteparin Dalteparin administered subcutaneously daily	Drug: Dalteparin Dalteparin 200 IU/kg/day followed by 150 IU/kg/day Other Names: Fragmin

Arm

Intervention/Treatment

Experimental: Abelacimab

Abelacimab intravenous administration followed by monthly administration of the same dose subcutaneously

Biological: Abelacimab

Abelacimab 150 mg

Other Names:

MAA868

Active Comparator: Dalteparin

Dalteparin administered subcutaneously daily

Drug: Dalteparin

Dalteparin 200 IU/kg/day followed by 150 IU/kg/day

Other Names:

Fragmin

Outcome Measures

Primary Outcome Measures

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 [6 months]

Secondary Outcome Measures

Time to first event of ISTH-adjudicated major or clinically relevant non-major (CRNM) bleeding events [6 months]
Net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 acute 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 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:

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 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 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 in the 4 weeks preceding 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 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 of <3 months at randomization
Calculated creatinine clearance (CrCl) <30 mL/min
Platelet count <50,000/ mm3
Hemoglobin <8 g/dL
Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase ≥3 times and/or bilirubin ≥2 times the upper limit of normal 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.