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 (ASTER)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Anthos Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

10 Aug 2022 → 5 Feb 2026

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509569-19-00

EudraCT number

2021-003076-14

ClinicalTrials.gov

NCT05171049

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Pharmacogenetic, Pharmacodynamic, Safety, Efficacy, Pharmacokinetic

The primary objective of this study is to assess whether abelacimab is non-inferior to apixaban for preventing VTE recurrence at 6 months post randomization in patients with cancer and recently diagnosed VTE. If non-inferiority is demonstrated, then superiority will be assessed.

Conditions and MedDRA coding

venous thromboembolism (VTE)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female subjects ≥18 years old or another legal maturity age according to the country of residence
2. Confirmed diagnosis of cancer (by histology or 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 oCurrently 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.
3. Confirmed symptomatic or incidental proximal lower limb DVT (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic or incidental PE of a segmental, or larger pulmonary artery, and/or a confirmed symptomatic or incidental PE of two or more subsegmental pulmonary arteries. Patients are eligible within 120 hours from diagnosis of the qualifying VTE.
4. Anticoagulation therapy with a therapeutic dose of DOAC for at least 6 months is indicated.
5. Able to provide written informed consent.

Exclusion criteria 24

1. 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, fondaparinux, DOAC, or other anticoagulants
2. An indication to continue treatment with therapeutic doses of an anticoagulant other than that used for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical heart valve, prior VTE)
3. Platelet count <50,000/mm3 at the screening visit
4. PE leading to hemodynamic instability (systolic blood pressure [BP] <90 mmHg or shock)
5. Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within 4 weeks preceding screening
6. Brain trauma, or a cerebral or a spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia in the 4 weeks preceding screening
7. Need for aspirin in a dosage of more than 100 mg/per day or any other antiplatelet agent alone or in combination with aspirin
8. Primary brain cancer or untreated intracranial metastases at baseline
9. Acute myeloid or lymphoid leukemia at baseline
10. Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks
11. Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization.
12. Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
13. Life expectancy <3 months at randomization
14. Calculated creatinine clearance (CrCl) <30 mL/min (Cockcroft-Gault equation) at the screening visit
15. Hemoglobin less than 8 g/dL at the screening visit
16. Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and/or bilirubin level 2 times or more higher the upper limit of the normal range at the screening visit in absence of clinical explanation
17. Uncontrolled hypertension (systolic BP>180 mm Hg or diastolic BP >100 mm Hg despite antihypertensive treatment)
18. 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).
19. 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
20. Pregnant or breast-feeding women
21. Patients known to be receiving strong dual inducers or inhibitors of both CYP3A4 and P-gp
22. History of hypersensitivity to any of the study drugs (including apixaban) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for apixaban
23. Subjects with any condition that as judged by the Investigator would place the subject at increased risk of harm if he/she participated in the study
24. 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 noninterventional or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first event of centrally adjudicated VTE recurrence through 6 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Anthos Therapeutics Inc.

Sponsor organisation

Anthos Therapeutics Inc.

Address

55 Parkway Terrace Suite 103

City

Cambridge

Postcode

02138-3350

Country

United States

Scientific contact point

Organisation

Anthos Therapeutics Inc.

Contact name

Anthos Therapeutics Information Desk

Public contact point

Organisation

Anthos Therapeutics Inc.

Contact name

Anthos Therapeutics Information Desk

Third parties 3

Locations

12 EU/EEA countries · 111 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Temporary halts 12 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 150 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications