AMI-DC in Patients With Anterior Wall Myocardial Infarction (AMI-DC)

A Multi-center, Controlled, Open, Phase I Clinical Trial to Assess the Safety of AMI-DC (Autologous Dendritic Cells) Treatment in Patients With Acute Anterior Wall ST-segment Elevation Myocardial Infarction Who Received Reperfusion by Primary Percutaneous Coronary Intervention (PCI)

The purpose of this trial is to assess the safety of AMI-DC treatment. The participants who voluntarily sign the consent form will be screened according to the inclusion/exclusion criteria then allocated either to the experimental group (drug therapy and AMI-DC therapy) or to the control group (drug therapy only). Both the experimental group and the control group are treated with standard medical therapy after PCI. The experimental group will be hospitalized for 4-5 days after 1st injection, and 1 day after 2nd injection. Vital signs are collected after 30 minutes, 1 hour, 2 hours and 4 hours after the 1st and 2nd injections and the subjects will be monitored 24 hours for safety assessment. The identical examination will also be performed in the control group and the results will be collected.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction
• Intervention / Treatment: Biological: Autologous peripheral blood-derived tolerogenic dendritic cells

Detailed Description

The registration of study subjects follows two stages (stages A & B). In Stage A, 6 subjects in the experimental group and 3 subjects in the control group will sequentially be registered, then will be monitored for 10 weeks to assess safety. If Stage A passes the safety assessment, the rest will be recruited and randomly allocated to either experimental or control group in Stage B.

Approximately 300cc of whole blood will be collected only from patients assigned to the experimental group. The amount of blood collection can be supervised and adjusted at the discretion of the investigators. Collected blood will be cultured for 4 days to generate the dendritic cells. Then, 5~10x106 cells are administered subcutaneously at 1-4 sites in the left axillary regions between 5-7 days after PCI and between 12-14 days after PCI.

Echocardiography and cardiac MRI will be examined for any signs of adverse reaction to ensure safety and evaluate cardiac functions at baseline and after 6 months.

• In stage A, 6 people are sequentially allocated to the experimental group and 3 people are sequentially allocated to the control group.
• The experimental group are monitored for 10 weeks following the 2nd AMI-DC to assess safety. Stage B is implemented once determined safe to proceed.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Eun Ho Choo, M/D/; Phone Number: +82222588206; Email: cmcchu@catholic.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
    • Recruiting
    • Eun Ho Choo
    • Contact: Eun Ho Choo; Phone Number: +82222588206; Email: cmcchu@catholic.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Volunteers who qualify all the following conditions

  1. Between the ages 19 through 80

     Patients within 24 hours from primary PCI with a diagnosis of acute anterior wall ST-segment elevation myocardial infarction and systolic dysfunction:

     acute myocardial infarction patient with an electrocardiogram (12-lead ECG) result corresponding to any of the following (ST-segment elevation 0.1 mV in two or more limb leads or 0.2 mV elevation in two or more contiguous precordial leads)

  2. Left ventricular ejection fraction (LVEF) below 50% by echocardiography
  3. Hemodynamically stable (SBP >100 mmHg, HR <110 bpm, SO2 >95%)
  4. Able-bodied for collection of approximately 300cc of blood for generation of autologous dendritic cells who qualify the following conditions
• Body weight: 50 kg or above for men, 45 kg or above for women
• Hb level of 12.0 g/dL or above 5) Signed the written consent form for this clinical trial

Exclusion Criteria:

• Volunteers who correspond to any of the following conditions

  1. LV thrombus
  2. Difficulty in accessing femoral artery for sheath insertion due to peripheral artery disease
  3. Previous history of PCI, CABG due to myocardial infarction
  4. Renal failure: serum Creatinine >2.5 mg/dL
  5. Acute or chronic infections
  6. Known contraindications to MRI
  7. Hemorrhagic disorders (PT INR >2)
  8. History of malignant tumor within 5 years
  9. A life expectancy of 1 year or less
  10. Tested positive with HIV, HBV, HCV and/or syphilis
  11. Autoimmune disease
  12. Pregnant or nursing mothers
  13. Participated in other clinical trials within past 30 days
  14. Deemed unfit for this clinical trial by the investigators
  15. Disagreed to use an approved method of contraception (Men: vasectomy, double diaphragm, or effective contraception used by the partner. Women: IUD, IUS or hormonal contraceptives) during the trial period.
  16. Moderate-to-severe liver disease (ALT is more than 5 times the upper limit of normal)
  17. Acute myocardial infarction patients at high bleeding risk with Hb 11g/dL or more Use or are scheduled to use oral anticoagulants for a long period of time Spontaneous hemorrhage that required hospitalization or blood transfusion within the past 6 months Thrombocytopenia (platelet count of <100x109/L) Liver cirrhosis with portal hypertension Severe ischemic stroke within the past 6 months, with spontaneous intracerebral hemorrhage and cerebrovascular malformation Major surgery or severe injury within the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMI-DC; Infusion of AMI-DC + Guideline directed optimal medical therapy	Biological: Autologous peripheral blood-derived tolerogenic dendritic cells; AMI-DC, autologous dendritic cell product Inject 7.5 x 106 cells hypodermically to 1~4 sites in the left axillary lymph node between 5-7 days after PCI and 12-14 days after PCI. . The administration must be done within 30 minutes after fully liquified.
No Intervention: Standard treatment; Control, Guideline directed optimal medical therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Outcome 1	Occurrence of Ventricular Arrhythmias, Perforation, Myocardial Ischemia, or Any sign of infection that occur during the entire study period	Up to 6 months
Primary Safety Outcome 2	Occurrence of Ventricular Arrhythmia or Bradyarrhythmia in 24-hour Holter monitoring at 12 weeks.	Week 12
Primary Efficacy Outcome	Cumulated incidence ratio of MACE (death from any cause, HF admission, VT/VF, stroke) at 6 months	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in infarct size	Change in infarct size measured by MRI between the baseline and 6 months.	up to 6 months
Change in left ventricular ejection fraction	Changes in left ventricular ejection fraction (in percent) by echocardiography/MRI between the baseline and 6 months.	up to 6 months
Change in LV chamber	Changes in left ventricular end-systolic (milliliter)/end-diastolic volume (milliliter) measured by echocardiography/MRI between the baseline and 6 months.	up to 6 months
Change in LV wall motion	Changes in WMSI measured by echocardiography/MRI between the baseline and 6 months.	up to 6 months
Change in polarization of lymphocyte by FACS	Changes in polarization of lymphocyte by FACS (in percentage) at baseline (before the 1st AMI-DC administration), before the 2nd AMI-DC administration, at 3 weeks, and at 12 weeks.	up to 12 weeks
Change in serum cytokine	Changes in IL-1, TNF-a, IL-6, and IL-10 (in picogram per milliliter) by ELISA at baseline (before the 1st AMI-DC administration), before the 2nd AMI-DC administration, at 3 weeks, and at 12 weeks.	up to 12 weeks
Change in white blood cell count	Changes in white blood cell count, neurtrophil count, and lymphocyte (number per liter) count between the baseline and 6 months.	up to 6 months
Change in C-reactive protein (CRP)	Changes in CRP (milligram per liter) between the baseline and 6 months.	up to 6 months
Change in NT-proBNP	Changes in NT-pro-BNP (picogram per liter) between the baseline and 6 months.	up to 6 months
Change in patients' HF symptom	Changes in NYHA functional class at each visit	up to 6 months

Collaborators and Investigators

• Sponsor: The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): October 30, 2023

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 21, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: AMI-DC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No