Atibuclimab for Heart Attack

Recruiting at 1 trial location

Overseen By Garry Redlich

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Implicit Bioscience

Must not be taking: Immunosuppressives, Anti-inflammatories

Disqualifiers: Heart failure, Valve disease, Infections, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have used immunosuppressive or anti-inflammatory drugs recently, you may not be eligible to participate.

How is the drug Atibuclimab unique for treating heart attacks?

Atibuclimab is unique because it targets CD14, a molecule involved in the body's immune response, which may help reduce inflammation and improve outcomes after a heart attack. This approach is different from standard treatments that primarily focus on restoring blood flow and managing symptoms. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults who've had a severe type of heart attack known as ST-elevation myocardial infarction (STEMI) and have been treated with stent placement. Specific eligibility criteria are not provided, but typically participants must meet certain health standards to be included.

Inclusion Criteria

I am scheduled for a standard heart attack treatment including a procedure to open my heart's arteries.

TIMI grade 0 (no flow) or grade 1 (penetration without perfusion) of the culprit artery on initial coronary angiogram

I have had a heart attack confirmed by an ECG.

Exclusion Criteria

I have not had major blood vessel surgery in the last 4 weeks.

Body weight >300 pounds (weight limit of the PET/CT table)

My kidney function is normal and my liver tests are not severely abnormal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single IV infusion of IC14 (atibuclimab) or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including biomarker assessments and cardiac function evaluations

12 weeks

Multiple visits (in-person) on Day 4, 15, 29, and 90

Optional Imaging

Optional CCR2+ myocardial imaging to assess myocardial infiltration

15 days

1 visit (in-person) on Day 15

Treatment Details

Interventions

• Atibuclimab

Trial Overview The study is testing Atibuclimab (IC14), an anti-CD14 monoclonal antibody, given once via IV at 20 mg/kg, against a placebo consisting of 150 mL saline solution also given once via IV. The aim is to see if Atibuclimab can prevent further damage to heart muscle and improve heart function.

Participant Groups

Group I: Experimental drug intervention Experimental Treatment 1 Intervention

monoclonal antibody against CD14

Group II: Placebo Placebo Group 1 Intervention

Identical-appearing normal saline for injection, intravenous, once

Atibuclimab is already approved in United States for the following indications:

Approved in United States as Atibuclimab for:

• Acute Decompensated Heart Failure (clinical trial phase, not yet approved)

Who Is Running the Clinical Trial?

Implicit Bioscience

Lead Sponsor

Trials

12

Recruited

140+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Findings from Research

In a study using a mouse model of heart failure after myocardial infarction, 71% of male and 44% of female mice developed cardiac autoantibodies (cAAbs) against cardiac troponin I, which were linked to worse cardiac remodeling and prognosis.

Treatment with rapamycin significantly reduced the production of these cAAbs, leading to improved survival and reduced cardiac inflammation and remodeling, suggesting a potential therapeutic approach for managing heart failure related to cAAbs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Autoantibodies Against Cardiac Troponin I in Post-Myocardial Infarction Heart Failure: Evaluation in a Novel Murine Model and Applications in Therapeutics. Furusawa, S., Ikeda, M., Ide, T., et al.[2023]

cMyBP-C autoantibodies (AAbs) were significantly present in patients with acute coronary syndrome (ACS), especially those with ST-elevation myocardial infarction (STEMI), indicating a potential early marker for cardiac damage.

The presence of cMyBP-C-AAbs was associated with reduced left ventricular ejection fraction (LVEF) and higher levels of myocardial infarction biomarkers, suggesting they could predict worsening cardiac function and patient outcomes before an infarction occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome. Lynch, TL., Kuster, DWD., Gonzalez, B., et al.[2020]

In a study of 491 patients with first ST-elevation myocardial infarction (STEMI), autoantibodies against the β1-adrenoceptor (β1-aab) were found in 39.1% of patients, while cardiac troponin-I autoantibodies (anti-cTnI) were present in 19.1%, indicating their prevalence in this condition.

Both β1-aab and anti-cTnI were identified as independent predictors of left ventricular remodeling after STEMI, but only β1-aab was strongly associated with major adverse cardiovascular events (MACEs), suggesting its potential role in worsening outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prognostic value of autoantibodies against β1-adrenoceptor and cardiac troponin-I for clinical outcomes in STEMI. Fan, Y., Chen, Y., Wan, Z., et al.[2017]

In a study of 1072 patients suspected of having non-ST segment elevation acute myocardial infarction (NSTEMI), the autoantibodies anti-apoA-1 IgG and anti-PC IgM showed very low diagnostic accuracy for NSTEMI, with area under the curve (AUC) values of 0.50 and 0.53, respectively, indicating they are not effective for diagnosis.

The same autoantibodies also demonstrated low prognostic accuracy for predicting major adverse cardiovascular events (MACE) during a 1-year follow-up, suggesting they do not provide useful information for patient outcomes in NSTEMI cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic and prognostic value of autoantibodies anti-apolipoprotein A-1 and anti-phosphorylcholine in acute non-ST elevation myocardial infarction. Rubini Gimenez, M., Pagano, S., Virzi, J., et al.[2015]

In a study of 99 patients with autoimmune myocarditis (AM), the presence of autoantibodies (AAB) with catalytic activity was found to correlate with the severity of the disease, particularly in malignant cases where 73% showed high specific activity of protabzymes.

The evaluation of catalytic activity of AAB can serve as a valuable tool for assessing the stage and prognosis of AM, as it helps differentiate between malignant, benign, and myocardiosclerosis forms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Catalytic autoantibodies in autoimmune myocarditis: clinical and pathogenetic implications]. Kalinina, EV., Ponomarenko, NA., Durova, OM., et al.[2006]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cardiac Autoantibodies Against Cardiac Troponin I in Post-Myocardial Infarction Heart Failure: Evaluation in a Novel Murine Model and Applications in Therapeutics. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

The prognostic value of autoantibodies against β1-adrenoceptor and cardiac troponin-I for clinical outcomes in STEMI. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Diagnostic and prognostic value of autoantibodies anti-apolipoprotein A-1 and anti-phosphorylcholine in acute non-ST elevation myocardial infarction. [2015]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Catalytic autoantibodies in autoimmune myocarditis: clinical and pathogenetic implications]. [2006]