The goal of this clinical trial is to test IC14 (atibuclimab) in patients with arrhythmogenic cardiomyopathy (ACM) and who have an implantable cardoverter/defibrillator in place. ACM is also called arrhythmogenic right ventricular dysplasia (ARV) or arrhythmogenic right ventricular cardiomyopathy (ARVC). The main questions the study aims to answer are the effect of treatment on blood markers of inflammation, safety, and pharmacokinetics. There will also be measurements of myocardial imaging of C-C chemokine receptor type 2 (CCR2+) immune cells (optional), monitoring of cardiac arrhythmias using the patient's pre-existing intracardiac cardioverter/defibrillator (ICD) and a Holter monitor, electrocardiogram (ECG), echocardiogram (ECHO), and blood tests. Results will be compared to baseline; there is no inactive placebo treatment group.

Participants will be asked to undergo screening and baseline testing, then receive 4 intravenous infusions with blood measurements before and after the infusion (including 24, 48, and 72 hours and 7, 14, and 28 days). Participants will be offered specialized scanning of the heart muscle, and will be asked to provide recordings from their ICD, undergo Holter monitoring twice, and have electrocardiograms (ECG), echocardiograms (ECHO) and blood tests.

This proof-of-concept study will evaluate the safety, pharmacokinetics, and preliminary efficacy of IC14 administered via IV infusion in patients with ACM.

In preclinical studies, anti-CD14 treatment prevented the development of ventricular dysfunction and cardiac damage in a mouse model of arrhythmogenic cardiomyopathy.

The objective of this study is to determine whether IC14 treatment reduces markers of inflammation and disease biomarkers in ACM patients treated with IC14. Secondary objectives are to further characterize the effect of IC14 treatment on CCR2+ cell myocardial infiltration measured by myocardial positron emission tomography (PET)/CT imaging, ventricular premature contractions (VPCs), other arrhythmias, ICD discharges, NYHA functional classification, and quality of life.

To characterize safety of IC14, the following assessments are to be performed: clinical biochemistry (safety analyses), ECG, ECHO, adverse events (AEs), serious adverse events (SAEs), and formation of anti-drug antibodies.

Finally, pharmacokinetic/pharmacodynamic parameters will be conducted. These include blood test measurements levels of the drug and its binding to its target in the serum and on cells.

This study will assign 5 patients to intravenous (IV) administration of IC14 (atibulcimab) at 20 mg/kg. The study drug will be administered every three weeks via IV infusion, for a total of 4 infusions (12 weeks of treatment).

Inclusion Criteria:

Patients are eligible for the study if all of the following criteria are met:

1. Age ≥ 18 years

2. Diagnosis of arrhythmogenic cardiomyopathy and: 1) meeting the 2020 Modified Task Force Criteria as affected;

3. Left ventricular ejection fraction of ≥30%

4. Functioning implantable cardioverter/defibrillator with remote interrogation capability

5. One of the following: 1) a history of ventricular tachycardia or ventricular fibrillation (VF); 2) ≥500 ventricular premature contractions (VPCs) in 24 hours on the most recent 24-hour Holter monitor recording; or 3) C-reactive protein >=1.5 mg/mL

6. Agreement by subject, physician, and cardiologist to not change concomitant ACM medications or to conduct catheter ablation during study participation unless needed for management of life-threatening conditions

7. Capable and willing to provide informed consent

8. Capable of completing study visits

9. Females participating in the study must meet one of the following criteria:

   1. Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy, or tubal ligation) for at least 6 months or postmenopausal (postmenopausal females must have no menstrual bleeding for at least 1 year) or
   2. If not postmenopausal, agree to use a double method of contraception, one of which is a barrier method (e.g., intrauterine device plus condom, spermicidal gel plus condom) until 30 days after the IC14 treatment and have negative human chorionic gonadotropin (β-hCG) test for pregnancy at Screening

10. Males who have not had a vasectomy must use appropriate contraception methods (barrier or abstinence) until 30 days after IC14 treatment

Exclusion Criteria:

A patient fulfilling any of the following criteria is to be excluded from enrollment in the study:

1. Prior myocardial infarction
2. Receiving continuous infusion of antiarrhythmic medication at time of enrollment
3. Previous major vascular intervention within 4 weeks
4. NYHA heart failure class IV, except palpitations
5. Major surgery within 6 weeks
6. Patient has participated in any study using an investigational drug or device within 30 days
7. Life expectancy of less than 1 year due to non-cardiac pathology
8. History of allergic reaction to atibuclimab (IC14) or any monoclonal antibody drug product or other CD14-derived drug product or any component used in the study (including contrast media)
9. Known severe renal (creatinine clearance <30 mL/min/m2) or hepatic insufficiency as well as alanine transaminase (ALT)/aspartate transaminase (AST) elevations ≥ 3x upper limit normal (ULN); isolated AST elevation is not considered an exclusion criterion from study participation
10. Current or planned use of continuous high-dose corticosteroids (short courses of corticosteroids are allowable)
11. Chronic immunosuppression with disease-modifying anti-rheumatic drugs (DMARDS)
12. Any clinically significant abnormality identified at the time of Screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study
13. Patients who will be inaccessible due to geographic or social factors during treatment or follow-up