Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202312651823009 Date of Registration: 14/12/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome
Official scientific title A Phase 3, Randomized, Double-blind, Placebo-controlled, Event-driven Study to Demonstrate the Efficacy and Safety of Milvexian, an Oral Factor XIa Inhibitor, After a Recent Acute Coronary Syndrome
Brief summary describing the background and objectives of the trial The purpose of this study is to evaluate that milvexian is superior to placebo, in addition to standard-of-care, in reducing the risk of major adverse cardiovascular event (MACE) (the composite of cardiovascular [CV] death, myocardial infarction [MI], and ischemic stroke). As of 07 December 2021, 4,114 participants have been included in the milvexian clinical program. Of the 4,114 participants, 3,229 received milvexian, of which 660 participants were exposed to milvexian in the Phase 1 studies and 2,569 participants were exposed to milvexian in the Phase 2 and 2a studies. Bleeding events reported in the milvexian clinical development program were mostly located around a surgical site or in the gastrointestinal tract. Four types of serious bleeding were assessed as adverse drug reactions: gastrointestinal bleeding, procedural hemorrhage, nervous system disorder bleeding (hemorrhagic transformation of ischemic stroke and subdural hematoma), and hematuria.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) LIBREXIA ACS
Disease(s) or condition(s) being studied Cardiology
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 08/03/2023
Actual trial start date 08/03/2023
Anticipated date of last follow up 19/10/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 16000
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
70033093ACS3003 Sponsor
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Milvexian 50 milligrams (mg) Up to 3 years and 6 months Milvexian daily dose of 50 milligrams (mg) tablets will be administered orally, starting from Day 1 on every 13 weeks until global targeted endpoint date (GTED). 8000
Control Group Matching Placebo 50 milligrams (mg) Up to 3 years and 6 months Matching placebo tablets will be administered orally, starting from Day 1 on every 13 weeks until global targeted endpoint date (GTED). 8000 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria: - 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 (example, troponin I, troponin T, creatine kinase-MB [CK-MB]) above the upper limit of normal as determined by the local laboratory - 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 (example, carotid atherosclerosis, intracranial artery stenosis, g) conservative management (that is, no percutaneous intervention [PCI] or CABG after index ACS event), h) Any one or more of the following high-risk angiographic features i) total stent length of greater than (>) 30 millimeters (mm), ii) thrombotic target lesion, iii) bifurcation lesion treated with more than one stent, iv) calcified target lesion treated with atherectomy, v) treatment of obstructive left main or proximal left anterior descending artery for index ACS (or clinical diagnosis of an anterior STEMI) - All female participants of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (hCG) or urine test at screening - 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: - MI secondary to ischemia due to either increased oxygen demand or decreased supply (Type 2 MI) or periprocedural MI as the index ACS event - Planned CABG or staged PCI after randomization - Any condition that requires chronic anticoagulation at the discretion of the investigator and/or local guidelines - Conditions with a significant increased risk of bleeding (example, clinically significant bleeding within previous 3 months, known bleeding diathesis, et cetera) Adult: 18 Year(s)-44 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 23/05/2023 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
123 Amkor Road Pretoria 0157 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Time to first occurrence of any component of MACE will be reported. MACE is a composite of cardiovascular (CV) death, myocardial infarction (MI), and ischemic stroke. Up to 3 years 6 months during and post intervention
Secondary Outcome Time to the First Occurrence of Major Adverse Vascular Event (MAVE) Up to 3 years 6 months during and post intervention
Secondary Outcome Time to the First Occurrence of Composite of All-cause Mortality (ACM), Myocardial Infarction (MI) and Ischemic Stroke Up to 3 years 6 months during and post intervention
Secondary Outcome Time to Cardiovascular (CV) Death Up to 3 years 6 months during and post intervention
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Tiervlei Trial Centre Tiervlei Trial Centre , Tygervalley Health Centre, The View, 7th Floor, 43 Old Oak Road Bellville 7530 South Africa
JOHESE Unitas Room 203, Unitas Lifestyle Management Park Unit 4 Corner of Clifton and Cantonment Avenue, Lyttelton, Centurion 0157 South Africa
Adult Cardiology Research Universitas Private Hospital, 1st Floor Room F02, 1 Logeman Street Bloemfontein 9301 South Africa
Corbod research Room H01 Panorama Medi Clinic, Rothschild Boulevard, Panorama Cape Town 7500 South Africa
Helderberg Research Institute Room 101, Busamed Paardevlei Private Hospital 4 Gardner Williams Ave Paardevlei Somerset West 7130 South Africa
Garda RA 302A Linksfield Medical Centre, Linksfield West Johannesburg 2192 South Africa
Clinical Projects Research 37/42 Russell Street Worcester 6850 South Africa
Dr JM Engelbrecht Trial Site Suite 21, Block 3, Vergelegen Mediclinic Main Road Somerset West 7130 South Africa
TREAD Research Room 41, 8th Floor Green Avenue, Francie van Zijl Drive, Parow Cape Town 7500 South Africa
E17 Cardiac Clinic New Main Building, Groote Schuur Hospital, Anzio Observatory Cape Town 7529 South Africa
Coronary Care Unit Site 502, 94 Charlotte Maxeke Street Durban 4001 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Janssen Cilag International NV Janssen-Cilag International NV Turnhoutseweg 30 Beerse 2340 Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Janssen Cilag International NV Turnhoutseweg 30 Beerse 2340 Belgium Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Lesley Burgess lesley@treadresearch.com +27219317825 Room 41,8th Floor, Green Avenue Tygerberg Hospital Francie van Zijl Avenue
City Postal code Country Position/Affiliation
Cape Town 7500 South Africa National Principal Investigator
Role Name Email Phone Street address
Public Enquiries Lesley Burgess lesley@treadresearch.com +27219317825 Room 41,8th Floor, Green Avenue Tygerberg Hospital Francie van Zijl Avenue
City Postal code Country Position/Affiliation
Cape Town 7500 South Africa National Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Elliot Barnathan EBarnath@its.jnj.com 0019082551231 920 Route 202, South Raritan
City Postal code Country Position/Affiliation
New Jersey 08869 United States of America Study Responsible Physician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes 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 Study Protocol IPD Sharing Time Frame has not been entered. IPD Sharing Access Criteria has not been entered.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.janssen.com/clinical-trials/transparency No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information