A Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaLuate the effIcacy and safety of abeLacimab in high-risk patients with Atrial fibrillation who have been deemed unsuitable for oral antiCoagulation (LILAC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Anthos Therapeutics Inc.

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

31 Oct 2023 → ongoing

Decision date (initial)

2023-06-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Anthos Therapeutics

External identifiers

EU CT number

2023-503224-66-00

ClinicalTrials.gov

NCT05712200

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess whether abelacimab is superior to placebo for reducing the risk of ischemic stroke or SE in patients with AF who have been deemed unsuitable for oral anticoagulation therapy

Secondary objectives 5

1. To evaluate abelacimab versus placebo with regard to the composite of ischemic stroke, SE, MI, VTE, or acute limb ischemia
2. To evaluate abelacimab versus placebo with regard to net clinical outcome defined as the composite of ischemic stroke, SE, or Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding
3. To evaluate abelacimab versus placebo with regard to both cardiovascular (CV) mortality and all-cause mortality
4. To evaluate abelacimab versus placebo with regard to net clinical outcome defined as the composite of ischemic stroke, SE, MI, VTE, acute limb ischemia, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding
5. To evaluate the risk of bleeding with abelacimab versus placebo in patients with AF who have been deemed unsuitable for oral anticoagulation therapy.

Conditions and MedDRA coding

Atrial Fibrillation

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Patient is able to understand and has provided written informed consent to participate in the trial
2. 2. Diagnosed AF or atrial flutter (including documentation that diagnosis was based on an ECG or monitor recording, in medical history or at screening)
3. 3. Age 65-74 and CHA2DS2VASc ≥4 OR age ≥75 and CHA2DS2VASc ≥3
4. 4. Patient is judged by the responsible physician to be unsuitable for oral anticoagulation because the risks outweigh the benefits or the patient is unwilling to take oral anticoagulation AND this determination was made prior to and independent of this study
5. 5. At least 1 of the following: • Severe renal insufficiency (including documentation of creatinine clearance <30 mL/min by the Cockcroft-Gault formula in medical history or at screening) • Planned daily use of aspirin, a P2Y12 inhibitor, or other antiplatelet agent for the duration of the trial • History of bleeding from a critical area which includes the following (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome) or major gastrointestinal bleeding (defined as requiring hospitalization, intervention, transfusion or leading to permanent discontinuation of anticoagulation) • Other conditions associated with an increased risk of bleeding (e.g., chronic NSAID use (≥3 times per week); frailty; or history of multiple falls)
6. 6. Patient is judged by the responsible physician to be unsuitable for left atrial appendage (LAA) closure or occlusion device, an approved device is not available, or the patient is unwilling to undergo the procedure AND this determination was made prior to and independent of the study

Exclusion criteria 17

1. 1. AF due to an ongoing acute reversible cause (e.g., cardiac surgery, pulmonary embolism (PE), untreated hyperthyroidism, alcohol use)
2. 4. Any stroke within 14 days before randomization or TIA within 3 days before randomization
3. 5. Mechanical heart valve or valve disease that is expected to require mechanical valve replacement intervention (surgical or invasive) during the course of the study
4. 6. Patients with a medical condition other than AF for which chronic anticoagulation is indicated
5. 7. Known presence of an atrial myxoma or left ventricular thrombus
6. 8. History of or planned LAA closure or occlusion device
7. 9. Clinically unstable or active endocarditis or endovascular infection
8. 16. Any patients who are committed to an institution by either judicial or administrative authorities.
9. 10. Planned invasive procedure with potential for uncontrolled bleeding (e.g., major surgery) within the next 3 months
10. 11. Patients on dialysis at screening or who are planned to start dialysis within 6 months
11. 12. Use of other investigational drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
12. 13. History of hypersensitivity to any of the study drugs or its excipients, to drugs of similar chemical classes
13. 14. Women of child-bearing potential defined as all women physiologically capable of becoming pregnant.
14. 15. Any medical or psychiatric condition which in the judgment of the Investigator either requires urgent medical intervention/ hospitalization or may preclude patients from complying with study requirements for the duration of the study
15. 2. Patients who within 60 days prior to randomization (1) received a vitamin K antagonist [(VKA) e.g., warfarin phenprocoumon, acenocoumarol] or a direct oral anticoagulant (DOAC) such as dabigatran, rivaroxaban, apixaban, or edoxaban or (2) were newly diagnosed with AF
16. 3. Patients with an intracranial or intraocular bleed within the 3 months prior to (and including) screening or any history of spontaneous intracerebral hemorrhage at any time in the absence of antithrombotic treatment
17. 17. Patients who are employed by the sponsor or employed by the investigator or otherwise financially dependent on them

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary efficacy endpoint is the time to first occurrence of confirmed ischemic stroke or SE.
2. The primary safety endpoint is the time to first occurrence of adjudicated BARC type 3c/5 bleeding.

Secondary endpoints 1

1. The secondary efficacy endpoints include: • Composite of ischemic stroke, SE, MI, VTE, or acute limb ischemia • Composite of ischemic stroke, SE, or BARC type 3c/5 bleeding • Cardiovascular (CV) mortality • All-cause mortality • Composite of ischemic stroke, SE, MI, VTE, acute limb ischemia, or ISTH major bleeding"

Investigational products

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

Test 1

Placebo 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

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Anthos Therapeutics Inc.

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 10

Locations

16 EU/EEA countries · 223 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 207 files

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

Application history

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