A Phase I Study of Allogeneic Myocardium-Derived Mesenchymal Stem Cells (HB1011) in Patients With Ischemic Cardiomyopathy (HEART-1)
Prospective, Open-label, Dose-escalation, Single-center, Non-randomized Phase I Study to Evaluate Safety and Tolerability of Allogeneic Myocardium-derived Mesenchymal Stem Cells (HB1011) in Patients With Ischemic Cardiomyopathy
Ischemic cardiomyopathy occurs when the heart muscle is permanently weakened due to blocked coronary arteries that limit blood flow. Current treatments, including medications and lifestyle changes, can manage symptoms but cannot restore the damaged heart muscle.
Stem cell therapy offers a promising approach to repair and regenerate damaged heart tissue. This study will evaluate the safety and tolerability of HB1011 - an allogeneic myocardium-derived mesenchymal stem cell therapy - in patients with ischemic cardiomyopathy who are undergoing coronary artery bypass grafting (CABG) surgery. HB1011 will be injected directly into the damaged heart muscle during the CABG procedure. Participants will receive different doses of HB1011, starting from a lower dose and gradually increasing, to identify the safest and most appropriate dose for future studies.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Participation in this study will last approximately 12 months following treatment. Prior to surgery, potential participants will undergo a screening visit to confirm eligibility. Screening assessments will include a physical exam, review of medical history and current medications, blood tests, electrocardiogram (ECG), echocardiogram, and cardiac MRI. Eligible participants will be admitted to the hospital 1 to 2 days before their scheduled CABG surgery for final pre-operative assessments.
On the day of surgery, CABG will be performed as planned. Once the bypass procedure is complete and before chest closure, HB1011 will be injected directly into the damaged heart muscle through a transepicardial approach. Participants will be assigned to either a low-dose or high-dose group following a sequential dose-escalation design, with safety carefully monitored at each stage before proceeding to the next dose level. After receiving the injections, participants will remain hospitalized for post-operative monitoring and observation.
Following discharge, participants will return for scheduled outpatient visits at 1, 3, 6, 9, and 12 months after surgery. At each visit, safety and tolerability will be assessed through physical exams, blood tests, and cardiac evaluations. Exploratory assessments of heart function, including echocardiogram and cardiac MRI, will be performed at selected time points to evaluate any changes over the course of the study.
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: HeeJung Kim, CTO
- Numéro de téléphone: +82-711-7734
- E-mail: hierabio@hierabio.com
Lieux d'étude
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Gyeonggi-do
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Seongnam-si, Gyeonggi-do, Corée du Sud, 13620
- Recrutement
- Seoul National University Bundang Hospital
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Contact:
- HyoungWoo Chang, Professor
- Numéro de téléphone: +82-31-787-7139
- E-mail: chang.hyoungwoo@gmail.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Scheduled to undergo coronary artery bypass grafting (CABG) surgery
- Left ventricular ejection fraction (LVEF) ≤ 40%
- Age 19 to 85 years, male or female
- Diagnosed with ischemic cardiomyopathy
- NYHA functional Class II-IV at screening
- Ability to understand the study and willing to provide written informed consent
Exclusion Criteria:
- New myocardial infarction within 28 days prior to screening, or unstabilized cardiac enzyme levels at screening
- Participation in another clinical trial involving an investigational drug or device within 6 months prior to screening
- Contraindication to cardiac MRI (e.g., pacemaker, severe claustrophobia)
- Pregnant, breastfeeding, or unwilling to use adequate contraception during the study
- History of malignancy within 5 years, severe allergic reaction, prior cardiac surgery (including CABG), stroke within 3 months, or incomplete recovery from major surgery within 12 weeks
- Significant comorbidities at screening, including severe ventricular arrhythmia, uncontrolled atrial fibrillation, severe or unstable COPD, congenital heart disease, active viral or severe infection, autoimmune disease, or active tuberculosis
- Active hepatitis B, hepatitis C, or HIV infection
- Systemic immunosuppressive therapy at protocol-defined high doses, or high-dose short-term steroid therapy within 4 weeks prior to treatment
- Suspected active infection within 48 hours before surgery
- Life expectancy less than 1 year due to non-cardiac conditions
- Requirement for concomitant major cardiac or aortic procedures at the time of CABG (e.g., valve repair/replacement, aortic surgery)
- Severe chronic renal impairment (eGFR < 30 mL/min/1.73m²), renal replacement therapy, or significant hepatic disease
- Hemodynamically unstable patients
- Severe pulmonary hypertension or conditions requiring resting oxygen therapy
- Panel reactive antibody (PRA) Class I or II ≥ 50%
- HbA1c > 10% in patients with diabetes
- Severe peripheral arterial disease with rest pain, ischemic ulcer, or gangrene
- Hypersensitivity to bovine-derived proteins
- Any other condition deemed unsuitable for participation by the investigator
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Group 1: Low Dose of HB1011
Drug: HB1011 (0.5 × 10⁷ cells), transepicardial intramyocardial injection at the time of CABG |
Biological: Lower dose of HB1011 injection Participants will receive between 5 intramyocardial injections of 1 million allogeneic myocardium-derived mesenchymal stem cells for a total of 0.5 x 10^7 cells. The injections will be administered following completion of CABG surgery. Biological: Higher dose of HB1011 injection Participants will receive between 5 intramyocardial injections of 2 million allogeneic myocardium-derived mesenchymal stem cells for a total of 1.0 x 10^7 cells. The injections will be administered following completion of CABG surgery. |
|
Expérimental: Group 2: High Dose of HB1011
Drug: HB1011 (1.0 × 10⁷ cells), transepicardial intramyocardial injection at the time of CABG |
Biological: Lower dose of HB1011 injection Participants will receive between 5 intramyocardial injections of 1 million allogeneic myocardium-derived mesenchymal stem cells for a total of 0.5 x 10^7 cells. The injections will be administered following completion of CABG surgery. Biological: Higher dose of HB1011 injection Participants will receive between 5 intramyocardial injections of 2 million allogeneic myocardium-derived mesenchymal stem cells for a total of 1.0 x 10^7 cells. The injections will be administered following completion of CABG surgery. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Adverse event, AE
Délai: 12 Months
|
Treatment-Emergent Adverse Event, TEAE, Adverse Drug Reaction, ADR, Serious Adverse Event, SAE, Serious Adverse Drug Reaction, SADR, Suspected Unexpected Serious Adverse Drug Reaction, SUSAR |
12 Months
|
|
DLT, Dose Limiting Toxicity
Délai: 12 Months
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DLT, Dose Limiting Toxicity |
12 Months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change in LVEF by Echocardiography
Délai: Baseline, 3, 6, and 12 months post-treatment
|
Change in left ventricular ejection fraction (LVEF) from baseline as measured by echocardiography |
Baseline, 3, 6, and 12 months post-treatment
|
|
Change in LVEF by Cardiac MRI
Délai: Baseline, 6, and 12 months post-treatment
|
Change in LVEF from baseline as measured by cardiac MRI |
Baseline, 6, and 12 months post-treatment
|
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Change in Infarct Scar Size (ISS)
Délai: Baseline, 6, and 12 months post-treatment
|
Change in infarct scar size from baseline as measured by delayed contrast-enhanced cardiac MRI |
Baseline, 6, and 12 months post-treatment
|
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Regional Wall Motion Abnormality (RWMA)
Délai: Baseline, 6, and 12 months post-treatment
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Change in regional wall motion abnormality at the site of HB1011 injection as assessed by echocardiography |
Baseline, 6, and 12 months post-treatment
|
|
NYHA Functional Classification
Délai: Baseline, 1, 3, 6, 9, and 12 months post-treatment
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Change in NYHA functional class based on patient-reported activity limitation (Improved / Unchanged / Worsened) |
Baseline, 1, 3, 6, 9, and 12 months post-treatment
|
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MACCE Incidence
Délai: Within 12 months post-treatment
|
Composite rate of major adverse cardiac and cerebrovascular events including death, hospitalization for heart failure, non-fatal recurrent MI, target vessel revascularization, and stroke |
Within 12 months post-treatment
|
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Mortality
Délai: Within 12 months post-treatment
|
Proportion of patients who died following CABG surgery, categorized as early mortality (within 30 days), in-hospital mortality, and late mortality (after 30 days) |
Within 12 months post-treatment
|
Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- HBC-1011-CTP-001
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
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