IC14 (Atibuclimab) in Arrhythmogenic Cardiomyopathy

NCT06275893 | Completed Phase 1 FDA Drug

• 1 other identifier: ACM01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Arrhythmogenic Cardiomyopathy; Arrhythmogenic Left Ventricular Cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy 1; ACM; ARVC; PKP2

Keywords

arrhythmia; cardiac genetic disorder; desmoglein mutation

Outcome Measures

Primary Outcomes (2)

• Safety: Treatment-emergent adverse events and serious adverse events

  Treatment-emergent adverse events and serious adverse events

  Baseline through 14 weeks

• Safety: Incidence of anti-drug antibodies

  Incidence of anti-drug antibodies

  Baseline, 4 weeks, and 14 weeks

Secondary Outcomes (18)

• Inflammatory biomarker C-reactive protein

  Baseline, 12 weeks

• CCR2+ Myocardial Imaging (optional)

  Baseline compared to 12 weeks

• Ventricular tachycardia

  Baseline compared to 12 weeks

• Ventricular premature contractions

  Baseline compared to 12 weeks

• Sustained and non-sustained ventricular tachycardia

  Baseline through 12 weeks

Study Arms (1)

IC14 (atibuclimab)

EXPERIMENTAL

IC14 (atibuclimab) 20 mg/kg intravenously every 3 weeks for 12 weeks (4 doses)

Biological: IC14

Interventions

IC14 BIOLOGICAL

recombinant monoclonal antibody directed against cluster of differentiation 14 (CD14) antigen

Also known as: (atibuclimab)

IC14 (atibuclimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible for the study if all of the following criteria are met:
• Age ≥ 18 years
• Diagnosis of arrhythmogenic cardiomyopathy and: 1) meeting the 2020 Modified Task Force Criteria as affected;
• Left ventricular ejection fraction of ≥30%
• Functioning implantable cardioverter/defibrillator with remote interrogation capability
• 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
• 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
• Capable and willing to provide informed consent
• Capable of completing study visits
• Females participating in the study must meet one of the following criteria:
• 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
• 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
• Males who have not had a vasectomy must use appropriate contraception methods (barrier or abstinence) until 30 days after IC14 treatment

You may not qualify if:

• A patient fulfilling any of the following criteria is to be excluded from enrollment in the study:
• Prior myocardial infarction
• Receiving continuous infusion of antiarrhythmic medication at time of enrollment
• Previous major vascular intervention within 4 weeks
• NYHA heart failure class IV, except palpitations
• Major surgery within 6 weeks
• Patient has participated in any study using an investigational drug or device within 30 days
• Life expectancy of less than 1 year due to non-cardiac pathology
• 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)
• Current or planned use of continuous high-dose corticosteroids (short courses of corticosteroids are allowable)
• Chronic immunosuppression with disease-modifying anti-rheumatic drugs (DMARDS)
• 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
• Patients who will be inaccessible due to geographic or social factors during treatment or follow-up

Sponsors & Collaborators

• Implicit Bioscience: lead

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Arrhythmogenic Right Ventricular Dysplasia, Familial, 1; Arrhythmias, Cardiac

Interventions

atibuclimab

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiomyopathies; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan Agosti, MD

  Implicit Bioscience

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label treatment with IC14. Participant outcomes will be compared to baseline. Pharmacokinetics will be measured.

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: February 23, 2024
• Study Start: March 29, 2024
• Primary Completion: August 15, 2025
• Study Completion: April 15, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)