A multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study comparing 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)

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

13 Sep 2022 → 11 Apr 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

2024-513992-42-00

EudraCT number

2021-003085-12

ClinicalTrials.gov

NCT05171075

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

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.

Conditions and MedDRA coding

venous thromboembolism (VTE) in patients with gastrointestinal/genitourinary cancer

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 other legal maturity age according to the country of residence
2. 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
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 PE, or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 120 hours from diagnosis of the qualifying VTE.
4. Anticoagulation therapy with LMWH for at least 6 months is indicated.
5. Able to provide written informed consent.

Exclusion criteria 25

1. Thrombectomy, insertion of a caval filter or use of a fibrinolytic agent to treat the current (index) DVT and/or PE.
2. More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, or other anticoagulants.
3. 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).
4. PE leading to hemodynamic instability (blood pressure [BP] <90 mmHg or shock)
5. Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within 4 weeks of screening
6. Brain trauma or a cerebral or spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening
7. Need for aspirin in a dosage of >100 mg/day or any other antiplatelet agent alone or in combination with aspirin
8. Bleeding requiring medical attention at the time of randomization or within the preceding 4 weeks
9. Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization
10. History of heparin-induced thrombocytopenia
11. Infective acute or subacute endocarditis at the time of presentation
12. Primary brain cancer or untreated intracranial metastasis
13. Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
14. Life expectancy <3 months at randomization
15. Calculated creatinine clearance (CrCl) <30 mL/min (Cockcroft-Gault equation) at the screening visit
16. Platelet count <50,000/mm3 at the screening visit
17. Hemoglobin <8 g/dL at the screening visit
18. Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase (ALT) ≥3 x and/or bilirubin ≥2 x upper limit of normal (ULN) at the screening visit in absence of clinical explanation
19. Uncontrolled hypertension (systolic BP >180 mm Hg or diastolic BP >100 mm Hg) despite antihypertensive treatment
20. 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)
21. 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.
22. Pregnant or breast-feeding women
23. 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
24. 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
25. 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 noninterventional studies or interventional studies 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 6 months post randomization

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

1 Health Plaza

City

East Hanover

Postcode

07936-1016

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 · 81 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

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

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