Evaluation of Orticumab on Coronary Inflammation in Post-Myocardial Infarction Patients with Elevated Fat Attenuation Index: A Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2025-520464-17-00
Protocol: ORT-2024-02
Sponsor: Abcentra LLC

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Diseases & Conditions

Myocardial infarction

Objectives

The primary objective of this study is to determine the clinical effect of **orticumab** treatment on inflammation in participants with prior myocardial infarction who exhibit elevated coronary inflammation, as assessed by the pericoronary Fat Attenuation Index (FAI) during Coronary Computed Tomography Angiography (CCTA). This is clinically relevant as it aims to address inflammation, a key factor in the progression of atherosclerotic cardiovascular disease, potentially improving patient outcomes by reducing the risk of further cardiac events.

Secondary objectives include:

Determining the clinical effects of orticumab on other coronary artery perivascular adipose tissue attenuation parameters measured during CCTA.
Assessing the safety and tolerability of orticumab in study participants.
Determining anti-drug antibodies (ADA) to orticumab.
Determining serum concentrations of orticumab.

These objectives are crucial for understanding the broader impact of orticumab on coronary health, its safety profile, and its pharmacokinetics, which are essential for evaluating its potential as a therapeutic agent.

Participants

The clinical trial involves a total of **56 participants** diagnosed with **Atherosclerotic Cardiovascular disease**. The study population includes both male and female adults aged 18 years and older. Participants are required to be more than 180 days post-myocardial infarction, specifically type-1 myocardial infarction, without subsequent unstable or severe angina. They must be on a stable cardiovascular treatment regimen and have a body mass index (BMI) of 40 kg/m² or less. The selection criteria also necessitate an evaluable pre-randomization CCTA with specific Fat Attenuation Index (FAI) scores. The trial does not include a vulnerable population, and participants are expected to adhere to certain lifestyle considerations, such as maintaining a stable medication regimen. The study does not provide specific details on diet or physical activity requirements.

Plans and Procedures

The clinical trial is designed to evaluate the **clinical effect** of **orticumab** in participants with a history of **myocardial infarction** and elevated coronary inflammation, as indicated by the Fat Attenuation Index (FAI) score assessed through Coronary Computed Tomography Angiography (CCTA). This study is a **randomized**, **double-blind**, **placebo-controlled** trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to last until December 31, 2026, with recruitment starting on September 15, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as being more than 180 days post-myocardial infarction and having a stable cardiovascular treatment regimen. The trial will include follow-up visits to monitor the participants' health and response to the treatment, with the primary endpoint being the percent change from baseline of the mean FAI score for the three coronary arteries after six months of treatment. Secondary endpoints will assess changes in FAI scores, CaRi-Heart risk score, and other clinical parameters.

The expected length of participant involvement is approximately six months, during which they will receive either **orticumab** or a placebo via injection. Participants may be terminated early from the study if they experience severe adverse events or if they fail to adhere to the study protocol. The end-of-study visit will involve a final assessment of the participants' health and the collection of data to evaluate the efficacy and safety of the treatment. This trial aims to provide valuable insights into the potential benefits of **orticumab** for reducing coronary inflammation in patients with **atherosclerotic cardiovascular disease**.

Treatment

The clinical trial involves the administration of **Orticumab**, an experimental medication formulated as a **solution for injection**. Orticumab is a protein-based therapeutic agent developed by ABCENTRA LLC, with the active substance identified as orticumab. The medication is administered via injection, with a maximum treatment period of 24 weeks. The specific dosage and frequency of administration are not detailed in the provided data. Orticumab is not a pediatric formulation and is not classified as an orphan drug. The trial aims to evaluate the effect of orticumab on coronary inflammation in participants with a history of myocardial infarction.

In addition to the experimental treatment, a **placebo** matching orticumab is utilized as a comparator in this double-blind, randomized, placebo-controlled study. The placebo is designed to mimic the pharmaceutical form of orticumab, ensuring blinding of both participants and investigators. The placebo is administered in the same manner as the active treatment, although specific details regarding its pharmaceutical form, dosage, and administration route are not provided. The use of a placebo allows for the assessment of orticumab's efficacy by comparing outcomes between the treatment and control groups.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the impact of **orticumab** on coronary inflammation in participants with a history of myocardial infarction. The primary endpoint for efficacy is the percent change from baseline of the mean Fat Attenuation Index (FAI) score for the three coronary arteries (right coronary artery [RCA], left anterior descending artery [LAD], and left circumflex artery [LCX]). This will be calculated as the average of the analyzable FAI scores across these arteries, comparing **orticumab** to placebo after six months of treatment.

Secondary endpoints include several measures of change from baseline in FAI scores, such as the mean absolute change and mean percent change in FAI score centile for **orticumab** compared to placebo. These changes will be assessed in specific vessels, including the most inflamed vessel, any vessel, and individual analyses for RCA, LAD, and LCX. Additional secondary endpoints involve changes in the CaRi-Heart risk score, treatment-emergent adverse events, and changes in systolic and diastolic blood pressure, pulse rate, clinical safety laboratory parameters, and physical examinations. Serum ADA titers and serum trough **orticumab** concentrations will also be measured at baseline and specified times over the six-month treatment period.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participant 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.
Participant 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.
Participant 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).
Participant must have an evaluable, pre-randomization CCTA with one of the following: • A 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 • A 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
Participant must have body mass index (BMI) ≤ 40 kg/m2.
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.

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Exclusion Criteria

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.
Percutaneous 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.
History of or planned coronary artery bypass grafting.
Documented episode of post-MI pericarditis in the 3 months before enrollment.
Presence of unstable or uncontrolled angina. Canadian CV society (CCS) angina class > 2.
Ongoing New York Heart Association Class IV HF.
Poorly controlled type 1 or type 2 diabetes mellitus (hemoglobin A1c >8.0%).
Increased risk of bleeding
History or presence of any of the following: a) Ongoing infection or febrile illness. b) Ongoing persistent or permanent atrial fibrillation or flutter. c) Cancer within 5 years before randomization, with the exception of non-melanoma skin cancer. d) Alcohol or substance abuse within 6 months before randomization, as judged by the investigator. e) Known 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) Active positive results on screening for serum hepatitis C core antibody. g) Clinically documented hepatitis B or HIV.
Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, as judged by the investigator
Blood pressure values at screening (taken as the average of triplicate measurements): a) Systolic blood pressure < 90 mmHg or > 180 mmHg. b) Diastolic blood pressure > 100 mmHg. c) One 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) Participants who are excluded based on elevated blood pressure may be rescreened following adequate treatment.
Participants with contraindications to CCTA
Use 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).
COVID-19 vaccine within 90 days of screening CCTA.
Participants with a confirmed positive COVID-19 test within 90 days of screening CCTA.
Receipt of any investigational device or therapy within 6 months or 5 half-lives before screening (whichever is longer).
Planned 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.
Participants who have previously been exposed to orticumab.
Participants who are legally institutionalized.
An 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.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Czechia	Recruiting	15 Sept 2025	35
Hungary	Recruiting	15 Sept 2025	23
Italy	Recruiting	15 Sept 2025	23
Poland	Recruiting	15 Sept 2025	23
Romania	Recruiting	15 Sept 2025	18
Spain	Recruiting	15 Sept 2025	45
Sweden	Recruiting	15 Sept 2025	17