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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Microvascular Dysfunction
• Intervention / Treatment: Biological: CLBS16

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lisata Therapeutics, Inc.
• Collaborators: Mayo Clinic; National Heart, Lung, and Blood Institute (NHLBI); Cedars-Sinai Medical Center
• Investigators: Study Director: Douglas W. Losordo, MD, Chief Medical Officer

Publications and helpful links

General Publications

• Henry TD, Bairey Merz CN, Wei J, Corban MT, Quesada O, Joung S, Kotynski CL, Wang J, Lewis M, Schumacher AM, Bartel RL, Takagi H, Shah V, Lee A, Sietsema WK, Losordo DW, Lerman A. Autologous CD34+ Stem Cell Therapy Increases Coronary Flow Reserve and Reduces Angina in Patients With Coronary Microvascular Dysfunction. Circ Cardiovasc Interv. 2022 Feb;15(2):e010802. doi: 10.1161/CIRCINTERVENTIONS.121.010802. Epub 2022 Jan 23.
• Rai B, Shukla J, Henry TD, Quesada O. Angiogenic CD34 Stem Cell Therapy in Coronary Microvascular Repair-A Systematic Review. Cells. 2021 May 8;10(5):1137. doi: 10.3390/cells10051137.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2018
• Primary Completion (Actual): December 10, 2019
• Study Completion (Actual): May 5, 2020

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: April 24, 2018
• First Posted (Actual): April 26, 2018

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: CLBS16-P01; 1R44HL135889-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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