A large global trial to evaluate the efficacy and safety of milvexian in reducing recurrent cardiovascular events in patients after a heart attack

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

21 Nov 2023 → 6 Feb 2026

Decision date (initial)

2023-08-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-501418-69-00

ClinicalTrials.gov

NCT05754957

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacodynamic, Prophylaxis, Pharmacoeconomic, Efficacy, Therapy, Pharmacokinetic

To demonstrate that milvexian is superior to placebo, in addition to standard-of-care, in reducing the risk of MACE (the composite of CV death, MI, and ischemic stroke)

Secondary objectives 4

1. To demonstrate that milvexian is superior to placebo, in addition to standard-of-care, in reducing the risk of MAVE (the composite of CV death, MI, ischemic stroke, MALE, and symptomatic VTE)
2. To determine whether milvexian reduces the risk of the composite of ACM, MI, and ischemic stroke compared to placebo
3. To determine whether milvexian reduces the risk of CV death compared to placebo
4. To determine whether milvexian reduces the risk of ACM compared to placebo

Conditions and MedDRA coding

Acute Coronary Syndrome

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participants must have an index event that meets all 3 of the following criteria within 7 days prior to randomization: a) Clinical syndrome consistent with spontaneous cardiac ischemia, b) Diagnosis of acute coronary syndrome (ACS) (that is, ST-elevation myocardial infarction [STEMI], non-STEMI, or unstable angina [UA]), c) Cardiac biomarker elevation (e.g., troponin I, troponin T, creatine kinase-MB [CK-MB]) above the upper limit of normal as determined by the local laboratory.
2. Participants must have at least 2 of the following risk factors: a) Age 65 or older, b) Diabetes mellitus, c) History of a prior myocardial infarction (MI) (other than index ACS event), d) Multivessel coronary artery disease (CAD), e) History of coronary artery bypass graft (CABG) surgery prior to index ACS event, f) History of peripheral artery disease (PAD) or cerebrovascular disease (eg., carotid atherosclerosis, intracranial artery stenosis), g) Conservative management (i.e., no percutaneous intervention [PCI] or CABG after index ACS event), h) Any one or more of the following high-risk angiographic features: a. Total stent length of greater than (>) 30 millimeters (mm), b. Thrombotic target lesion, c. Bifurcation lesion treated with more than one stent, d. Calcified target lesion treated with atherectomy, e. Treatment of obstructive left main or proximal left anterior descending artery for index ACS (or clinical diagnosis of an anterior STEMI)
3. All female participants of childbearing potential must have a negative highly sensitive serum B-hCG or urine test at screening
4. A female participant must not be pregnant, breastfeeding, or planning to become pregnant until 4 days (5 half-lives) after the last dose of study intervention

Exclusion criteria 4

1. MI secondary to ischemia due to either increased oxygen demand or decreased supply (Type 2 MI) or periprocedural MI as the index ACS event
2. Planned CABG or staged PCI after randomization
3. Any condition that requires chronic anticoagulation at the discretion of the investigator and/or local guidelines.
4. Conditions with a significant increased risk of bleeding (e.g., clinically significant bleeding within previous 3 months, known bleeding diathesis, etc.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to the first occurrence of MACE

Secondary endpoints 4

1. Time to the first occurrence of MAVE
2. Time to the first occurrence of ACM, MI, and ischemic stroke
3. Time to CV death
4. Time to ACM

Investigational products

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

Test 1

Placebo 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 11

Locations

20 EU/EEA countries · 317 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 275 files

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

Application history

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