Safety and Potential Bioactivity of CLBS16 in Patients With Coronary Microvascular Dysfunction and Without Obstructive Coronary Artery Disease

Study Overview
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Brief Summary
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This clinical trial will explore the safety and effect of GCSF-mobilized autologous ex vivo selected CD34 cells for the treatment of CMD in adults currently experiencing angina and with no obstructive coronary artery disease. Eligible subjects will receive a single intracoronary infusion of CLBS16.

Official Title
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An Open-Label Exploratory Clinical Study to Evaluate the Safety and Potential Bioactivity of CLBS16 in Patients With Coronary Microvascular Dysfunction (CMD) and Without Obstructive Coronary Artery Disease

Conditions
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Coronary Microvascular Dysfunction

Intervention / Treatment
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* Biological: CLBS16


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women age ≥18 History of and currently experiencing angina at least 3 times per week No obstructive coronary artery disease On stable medical therapy for 30 days prior to enrollment Must agree to use a reliable and acceptable method of contraception for the duration of participation Written informed consent Exclusion Criteria: Myocardial infarction within 90 days Prior evidence of obstructive heart disease including PCI or CABG (or planned PCI or CABG) Diagnosis of other specific cardiac disease Must meet LVEF and GFR requirements Current use of coumadin or DOACs Hypersensitivity to G-CSF, apheresis or study product components Positive for HIV, hepatitis B or hepatitis C Active inflammatory or autoimmune disease, or chronic immunosuppressive state Drug abuse Pregnant or lactating Malignant neoplasm within 5 years History of Sickle Cell Disease Participation in another clinical study within 90 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous CD34 cells<br>Open label active treatment arm. Subjects receive autologous CD34 cells. | Biological: CLBS16<br>* GCSF-mobilized autologous CD34 cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Coronary Flow Reserve | Coronary Flow Reserve (CFR) is a measure of coronary microvascular function. | Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Microvascular Function as Assessed by Intracoronary Administration of Acetylcholine |  | Day 180 | 
| Change From Baseline in Peripheral Arterial Tonometry |  | Day 180 | 
| Change in Angina Frequency From Baseline |  | 6 months | 
| Canadian Cardiovascular Society Angina Class | Canadian Cardiovascular Society angina class grading scale is assessed according to the following scores: Grade 1: Ordinary physical activity does not cause angina, such as walking and climbing stairs. Angina with strenuous or rapid or prolonged exertion at work or recreation Grade 2: Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, or in cold, or in wind, or under emotional stress, or only during the few hours after awakening. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions Grade 3: Marked limitation of ordinary physical activity. Walking one or two blocks on the level and climbing one flight of stairs in normal conditions and at normal pace Grade 4: Inability to carry on any physical activity without discomfort, anginal syndrome may be present at rest A higher grade is a worse outcome. | 6 months | 
| Change From Baseline in Seattle Angina Questionnaire | The SAQ quantifies patients' physical limitations caused by angina, the frequency of and recent changes in their symptoms, their satisfaction with treatment, and the degree to which they perceive their disease to affect their quality of life. Each scale is transformed to a score of 0 to 100, where higher scores indicate better function (eg, less physical limitation, less angina, and better quality of life). | 6 months | 
| Change From Baseline in SF-36 Scores | The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. | 6 months |