ASTER: A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE

Sponsor

Anthos Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05171049

Collaborator

Itreas (Other)

1,655

Enrollment

Locations

Arms

Anticipated Duration (Months)

137.9

Patients Per Site

6.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 3,multicenter, randomized, open-label, blinded endpoint evaluation study comparing the effect of abelacimab relative to apixaban on venous thromboembolism (VTE) recurrence and bleeding in patients with cancer associated VTE (ASTER)

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1655 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 Relative to Apixaban on Venous Thromboembolism (VTE) Recurrence and Bleeding in Patients With Cancer Associated VTE

Actual Study Start Date :

May 4, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Feb 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: Apixaban Apixaban administered orally twice a day	Drug: Apixaban Apixaban 10 mg followed by 5 mg Other Names: Eliquis

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: Apixaban

Apixaban administered orally twice a day

Drug: Apixaban

Apixaban 10 mg followed by 5 mg

Other Names:

Eliquis

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 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 acute 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 72 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 72 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
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 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 major surgery at baseline
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)
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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington DC VAMC	Washington	District of Columbia	United States	20422
2	University of Kentucky, Markey Cancer Center	Lexington	Kentucky	United States	40536-0093
3	Henry Ford Health System	Detroit	Michigan	United States	48202
4	Washington University	Saint Louis	Missouri	United States	63110
5	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
6	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
7	Sentara Norfolk General Hospital	Norfolk	Virginia	United States	23507
8	Gundersen Health System	La Crosse	Wisconsin	United States	54601
9	University of Calgary	Calgary	Alberta	Canada	T2N 1N4
10	Ottawa Hospital	Ottawa	Ontario	Canada	K1H BL6
11	Sault Area Hospital	Sault-Sainte-Marie	Ontario	Canada	P6A 0A8
12	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4