Clinical trial NCT06678074: Pilot Study of IC14 (Atibuclimab), an Anti-CD14 Monoclonal Antibody, to Treat STEMI
Official title: Phase 1b Pilot Study of Atibuclimab (IC14) for Treatment of ST-Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: STEMI
STEMI (ST Elevation MI)
STEMI - ST Elevation Myocardial Infarction (MI)
Stent Implantation
Keywords: atibuclimab
IC14
monoclonal antibody against CD14
anti-CD14
antiinflammatory
Lead sponsor: Implicit Bioscience
Sponsor class: INDUSTRY
Collaborators: name: Washington University School of Medicine
name: The Cleveland Clinic
First posted: 2024-11-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Adults who have had an ST-elevation myocardial infarction and were treated with stent placement will receive an intravenous infusion of a monoclonal antibody in order to prevent further heart muscle damage. The goal is to learn if this treatment improves some measures of heart function and inflammation. The study treatment patients will be compared to patients who receive placebo (inactive treatment).

Detailed description: Randomized, double-blind, placebo-controlled pilot study to evaluate the safety, exploratory efficacy, and pharmacokinetics of IC14 (atibuclimab) administered via a single IV infusion to patients with STEMI treated with percutaneous intervention. In additional to optional CCR2+ myocardial imaging, biomarkers, cardiac function and patient-reported outcome measures will be reported.

Eligibility criteria: Inclusion Criteria:

1. Acute myocardial infarction with ST elevation at the J-point in two contiguous leads as determined by ECG.
2. TIMI grade 0 (no flow) or grade 1 (penetration without perfusion) of the culprit artery on initial coronary angiogram
3. Symptom onset prior to PCI of ≤12 hours
4. Planned to receive the local standard of care for treatment of their STEMI and follow up which must include percutaneous coronary intervention (PCI)
5. Ability to infuse study drug within 12 hours of PCI
6. Age ≥18 years, willing and able to provide written informed consent and to comply with the protocol (i.e., reporting of symptoms)
7. Capable of completing study visits
8. Females participating in the study must meet one of the following criteria:

   1. Postmenopausal (postmenopausal females must have no menstrual bleeding for at least 1 year);
   2. Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy, or tubal ligation) for at least 6 months; or
   3. 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 treatment
9. Males who have not had a vasectomy must use appropriate contraception methods (barrier or abstinence) until 30 days after treatment

Exclusion Criteria:

An individual fulfilling any of the following criteria is to be excluded from enrollment in the study:

1. Killip Classification for Heart Failure Class III (acute pulmonary edema) or IV (cardiogenic shock)
2. Severe aortic or mitral valve disease
3. Failure to reperfuse, vascular dissection, cardiac perforation, cardiac arrest, requirement for mechanical circulatory support, or acute respiratory failure requiring ventilatory support
4. Major hemodynamic instability or uncontrolled ventricular arrhythmias
5. Planned or conducted thrombolytic therapy for treatment of this STEMI event
6. Planned or conducted coronary artery bypass graft
7. Previous major vascular intervention within the last 4 weeks
8. Major surgery within the last 6 weeks
9. Evidence of an active gastrointestinal or urogenital bleeding
10. Recent (\<14 days) use of immunosuppressive or anti-inflammatory drugs (including oral corticosteroids at a prednisone equivalent dose of ≥0.5 mg/kg/day but not including inhaled or low-dose oral corticosteroids, non-steroidal anti-inflammatory drugs, or colchicine).
11. Chronic inflammatory disorder (i.e., rheumatoid arthritis, systemic lupus erythematosus).
12. Active infection (of any type), including chronic/recurrent infectious disease (including HBV, HCV, and HIV/AIDS), but excluding HCV+ with undetectable plasma RNA.
13. Neutropenia (\<1,500/mm3 or \<1,000/mm3 in Black/African American patients).
14. Active malignancy, excluding carcinoma in situ \[any location\] or localized non-melanoma skin cancer
15. Participation in any study using an investigational drug or device within 30 days or within 5 half-lives of the investigational drug (whichever is longer) of entry into this study.
16. Life expectancy of less than 1 year due to non-cardiac pathology
17. History of allergic reaction to atibuclimab (IC14), any monoclonal antibody, or any other component used in the study (including contrast media)
18. Body weight \>300 pounds (weight limit of the PET/CT table)
19. Known severe renal (creatinine clearance \<30 mL/min) or hepatic insufficiency as well as alanine transaminase (ALT) elevation ≥ 3x upper limit of normal; isolated AST-elevation is not considered an exclusion criterion from study participation
20. 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: Day 1-29
Secondary outcomes:
measure: CCR2+ cell myocardial infiltration (optional)
timeFrame: 48 hours and Day 15
measure: Biomarker C-Reactive Protein
timeFrame: Day 4, 15, 29
measure: Biomarker White Blood Cell Count
timeFrame: Day 4, 15, and 29
measure: Biomarker Fibrinogen
timeFrame: Day 4, 15, 29
measure: Biomarker Interleukin 6
timeFrame: Day 4, 15, and 29
measure: Biomarker Interleukin-1
timeFrame: Day 4, 15, and 29
measure: Biomarker Troponin I
timeFrame: Day 4, 15, and 29
measure: Single-cell RNASeq
timeFrame: Day 4, 15, and 29
measure: Cardiac death or readmission for heart failure
timeFrame: Day 1-90
measure: Left Ventricular Ejection Fraction
timeFrame: Day 1, Day 90
measure: N-terminal pro B-type natriuretic peptide
timeFrame: Day 90
measure: New York Heart Association Class
timeFrame: Day 90
measure: Kansas City Cardiomyopathy Questionnaire
timeFrame: Day 90
Other outcomes:
measure: Pharmacokinetic profile of serum IC14 level, including serum half life and maximum serum concentration
timeFrame: baseline, 15 minutes, 6 hours, Day 4, Day 15, Day 22, Day 29
measure: Pharmacodynamics
timeFrame: Day 22, Day 29
measure: Immunogenicity
timeFrame: baseline, Day 29, Day 90
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
References: