ORTICUMAB for Atherosclerotic cardiovascular disease | Myocardial infarction

Inclusion criteria

• {"criterion_text":"- 1.\tParticipant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomization and must adhere to the schedules of activities.\n- 2.\tParticipant must be >180 days after presumed type-1 myocardial infarction (i.e., due to plaque rupture or erosion, either STEMI or NSTEMI) without subsequent unstable or severe angina (Canadian Cardiovascular Society Class 3 or 4) at the time of enrollment. Participants who have undergone PCI are allowed.\n- 3.\tParticipant must be on a stable cardiovascular treatment regimen consistent with local treatment guidelines for post-AMI patients (such as maximally tolerated statin and/or PCSK9 inhibitor medication for LDL reduction, antiplatelet medication, and hypertension treatment).\n- 4.\tParticipant must have an evaluable, pre-randomization CCTA with one of the following: •\tA quantifiable Fat Attenuation Index (FAI) Score greater than or equal to the 50th centile (per reference standard) for their age group in at least two coronary arteries or •\tA quantifiable Fat Attenuation Index (FAI) Score greater than or equal to the 75th centile (per reference standard) for their age group in at least one coronary artery\n- 5.\tParticipant must have body mass index (BMI) ≤ 40 kg/m2.\n- 6. Adult male and female participants ≥18 years of age at the Screening Visit: For female participants, the participant must not be pregnant or lactating and must be one of the following: a) Postmenopausal b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. c)Females of childbearing potential must have a negative serum or urine pregnancy test prior to the start of study drug, and agree to use a highly effective method of contraception from Baseline through 100 days after the last dose of study For male participants - Nonsterile male participants with sexual partners of childbearing potential must agree to use an adequate method of contraception such as condom, from Baseline through 100 days after last dose of the study drug."}

Exclusion criteria

• {"criterion_text":"- 1.      History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.\n- 10.\tAny clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator\n- 11.\tBlood pressure values at screening (taken as the average of triplicate measurements): a)\tSystolic blood pressure < 90 mmHg or > 180 mmHg. b)\tDiastolic blood pressure > 100 mmHg. c)\tOne triplicate retest (repeat of all 3) will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the participant may be randomized d)\tParticipants who are excluded based on elevated blood pressure may be rescreened following adequate treatment.\n- 12.\tParticipants with contraindications to CCTA\n- 13.\tUse of any of the following in the 180 days before randomization: IL-17 inhibitor, TNF inhibitor, IL-6 inhibitor, IL-1β inhibitor, methotrexate, cyclosporine, apremilast, colchicine, systemic steroids (topical steroid and inhaled steroid use is allowed).\n- 14.\tCOVID-19 vaccine within 90 days of screening CCTA.\n- 15.\tParticipants with a confirmed positive COVID-19 test within 90 days of screening CCTA.\n- 16.\tReceipt of any investigational device or therapy within 6 months or 5 half-lives before screening (whichever is longer).\n- 17.\tPlanned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed.\n- 18.\tParticipants who have previously been exposed to orticumab.\n- 19.\tParticipants who are legally institutionalized.\n- 2.\tPercutaneous coronary intervention or invasive diagnostic coronary angiogram planned after screening. Eligible participants who have an invasive diagnostic coronary angiogram performed in the absence of undergoing a new PCI may continue screening after the diagnostic angiogram has been performed or may be rescreened.\n- 20.\tAn employee or close relative of an employee of the sponsor, the CRO, or the study site, regardless of the employee or close relative's role.\n- 3.\tHistory of or planned coronary artery bypass grafting.\n- 4.\tDocumented episode of post-MI pericarditis in the 3 months before enrollment.\n- 5.\tPresence of unstable or uncontrolled angina. Canadian CV society (CCS) angina class > 2.\n- 6.\tOngoing New York Heart Association Class IV HF.\n- 7.\tPoorly controlled type 1 or type 2 diabetes mellitus (hemoglobin A1c >8.0%).\n- 8.\tIncreased risk of bleeding\n- 9.\tHistory or presence of any of the following: a)\tOngoing infection or febrile illness. b)\tOngoing persistent or permanent atrial fibrillation or flutter. c)\tCancer within 5 years before randomization, with the exception of non-melanoma skin cancer. d)\tAlcohol or substance abuse within 6 months before randomization, as judged by the investigator. e)\tKnown history of hypersensitivity reactions to other biologics, to human IgG preparations, or to any component of orticumab, or ongoing severe allergy as judged by the investigator. f)\tActive positive results on screening for serum hepatitis C core antibody. g)\tClinically documented hepatitis B or HIV."}

Primary endpoints

• {"endpoint_text":"- Percent change from baseline of the mean Fat Attenuation Index (FAI) score for the 3 coronary arteries (RCA, LAD, LCX), calculated as the average of the analyzable FAI scores (valid baseline and post-baseline FAI score) across the three main coronary arteries, for orticumab compared to placebo after 6 months of treatment","definition_or_measurement_approach":"Percent change from baseline of the mean FAI score for the three main coronary arteries (RCA, LAD, LCX), calculated as the average of analyzable FAI scores (valid baseline and post-baseline) across the three arteries; assessed at 6 months comparing orticumab versus placebo."}

Secondary endpoints

• {"endpoint_text":"- 1.\tChange from baseline for FAI, FAI score (mean absolute change and mean percent change) and FAI score centile for orticumab compared to placebo after 6 months of treatment in the following vessels: o\tGreatest change in most inflamed vessel o\tGreatest change in any vessel o\tRCA only analysis o\tLAD only analysis o\tLCX only analysis","definition_or_measurement_approach":"Change from baseline in FAI measures (mean absolute and percent change, and centile) at 6 months evaluated per vessel and by specified analyses (greatest change in most inflamed vessel, any vessel, and vessel-specific analyses)."}
• {"endpoint_text":"- 2.\tMean absolute change from baseline for mean FAI and mean FAI score, defined as the average of the analyzable vessels (with valid baseline FAI and post-baseline FAI) across the three main coronary arteries (RCA, LAD, LCX)","definition_or_measurement_approach":"Mean absolute change from baseline for mean FAI and mean FAI score across analyzable vessels (RCA, LAD, LCX); averaged across vessels with valid baseline and post-baseline FAI."}
• {"endpoint_text":"- 3. Change from baseline for CaRi-Heart risk score (mean absolute change and mean percent change) for orticumab compared to placebo after 6 months of treatment","definition_or_measurement_approach":"Change from baseline (mean absolute and percent change) in CaRi-Heart cardiovascular risk score at 6 months comparing orticumab vs placebo."}
• {"endpoint_text":"- 4. Number and percent of participants with treatment-emergent adverse events (TEAEs), and any serious adverse events","definition_or_measurement_approach":"Counts and percentages of participants experiencing TEAEs and any serious adverse events during the study period."}
• {"endpoint_text":"- 5. Change from baseline in systolic blood pressure, diastolic blood pressure and pulse rate measurements","definition_or_measurement_approach":"Change from baseline in vital sign measurements: systolic BP, diastolic BP, and pulse rate, measured at scheduled visits."}
• {"endpoint_text":"- 6. Change from baseline in clinical safety laboratory parameters","definition_or_measurement_approach":"Change from baseline in clinical safety laboratory parameters (clinical chemistry, hematology, coagulation) as measured in scheduled laboratory assessments."}
• {"endpoint_text":"- 7. Change from baseline in physical examinations","definition_or_measurement_approach":"Change from baseline in findings on physical examination at scheduled visits."}
• {"endpoint_text":"- 8. Serum ADA titers measured at baseline and at specified times over the 6-month treatment period","definition_or_measurement_approach":"Serum anti-drug antibody (ADA) titers measured at baseline and at pre-specified timepoints across the 6-month treatment period."}
• {"endpoint_text":"- 9. Serum trough orticumab concentrations following an orticumab dose","definition_or_measurement_approach":"Serum trough concentrations of orticumab measured following dosing at specified PK sampling times."}

Hungary

Earliest CTIS Part Ii Submission Date

31-07-2025

Latest Decision Or Authorization Date

22-08-2025

Processing Time Days

22

Number Of Sites

5

Number Of Participants

23

Romania

Earliest CTIS Part Ii Submission Date

28-07-2025

Latest Decision Or Authorization Date

25-08-2025

Processing Time Days

28

Number Of Sites

3

Number Of Participants

18

Poland

Earliest CTIS Part Ii Submission Date

28-07-2025

Latest Decision Or Authorization Date

22-08-2025

Processing Time Days

25

Number Of Sites

3

Number Of Participants

23

Italy

Earliest CTIS Part Ii Submission Date

16-05-2025

Latest Decision Or Authorization Date

27-08-2025

Processing Time Days

103

Number Of Sites

5

Number Of Participants

23

Sweden

Earliest CTIS Part Ii Submission Date

30-06-2025

Latest Decision Or Authorization Date

15-10-2025

Processing Time Days

107

Number Of Sites

3

Number Of Participants

17

Czechia

Earliest CTIS Part Ii Submission Date

29-07-2025

Latest Decision Or Authorization Date

03-11-2025

Processing Time Days

97

Number Of Sites

5

Number Of Participants

35

Spain

Earliest CTIS Part Ii Submission Date

23-07-2025

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

285

Number Of Sites

6

Number Of Participants

45

Primary sponsor

Full Name

Abcentra LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

4g Clinical LLC

Responsibilities

sponsorDuties codes: 3

Name

Fortrea Inc.

Responsibilities

Multiple operational responsibilities including ancillary supplies management and vendor management (sponsorDuties codes listed in CTIS)

Third parties

• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Caristo Diagnostics Ltd","duties_or_roles":"Imaging","organisation_type":"SME"}
• {"country":"Belgium","full_name":"AAC","duties_or_roles":"24 hour medical coverage","organisation_type":"Industry"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"PK, ADA testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Multiple sponsor duties (codes listed); ancillary supplies management, Vendor management","organisation_type":"Pharmaceutical company"}