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

• Sponsor: Caladrius Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03508609
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Cedars-Sinai Medical Center (Other), Mayo Clinic (Other)
• Enrollment: 20
• Locations: 2
• Arm: 1
• Actual Duration (Months): 24.5
• Patients Per Site: 10
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Microvascular Dysfunction	Biological: CLBS16	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 19, 2018
• Actual Primary Completion Date: Dec 10, 2019
• Actual Study Completion Date: May 5, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Coronary Flow Reserve [Day 180]

   Coronary Flow Reserve (CFR) is a measure of coronary microvascular function.

Secondary Outcome Measures

1. Change From Baseline in Microvascular Function as Assessed by Intracoronary Administration of Acetylcholine [Day 180]

2. Change From Baseline in Peripheral Arterial Tonometry [Day 180]

3. Change in Angina Frequency From Baseline [6 months]

4. Canadian Cardiovascular Society Angina Class [6 months]

   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.

5. Change From Baseline in Seattle Angina Questionnaire [6 months]

   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. Change From Baseline in SF-36 Scores [6 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Caladrius Biosciences, Inc.
• National Heart, Lung, and Blood Institute (NHLBI)
• Cedars-Sinai Medical Center
• Mayo Clinic

Investigators

• Study Director: Douglas W. Losordo, MD, Chief Medical Officer

Study Documents (Full-Text)

• Study Protocol - Aug 26, 2019
• Statistical Analysis Plan - May 25, 2020

More Information

Publications

None provided.

• Responsible Party: Caladrius Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT03508609
• Other Study ID Numbers: CLBS16-P01; 1R44HL135889-01
• First Posted: Apr 26, 2018
• Last Update Posted: Jan 8, 2021
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease

Study Results

Participant Flow

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Period Title: Overall Study
STARTED	20
COMPLETED	19
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 70%
>=65 years	6 30%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (12.72)
Sex: Female, Male (Count of Participants)
Female	17 85%
Male	3 15%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	19 95%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 5%
Asian	2 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	16 80%
More than one race	0 0%
Unknown or Not Reported	1 5%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	83.36 (23.377)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.52 (7.322)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Mean (Standard Deviation) [ratio]	0.62 (0.835)

2. Secondary Outcome

Title	Change From Baseline in Microvascular Function as Assessed by Intracoronary Administration of Acetylcholine
Time Frame	Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Mean (Standard Deviation) [% change in peak coronary blood flow]	9.4 (105.408)

3. Secondary Outcome

Title	Change From Baseline in Peripheral Arterial Tonometry
Time Frame	Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Mean (Standard Deviation) [Reactive Hyperemia Index (ratio)]	-0.19 (0.990)

4. Secondary Outcome

Title	Change in Angina Frequency From Baseline
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Mean (Standard Deviation) [angina episodes per day]	-2.34 (2.938)

5. Secondary Outcome

Title	Canadian Cardiovascular Society Angina Class
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Mean (Standard Deviation) [change in grade]	-1.21 (1.032)

6. Secondary Outcome

Title	Change From Baseline in Seattle Angina Questionnaire
Description	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).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Physical limitation scale	16.81 (20.956)
Angina stability scale	23.61 (40.649)
Angina frequency scale	18.33 (28.952)
Treatment satisfaction scale	12.83 (19.925)
Disease perception scale	23.68 (24.417)

7. Secondary Outcome

Title	Change From Baseline in SF-36 Scores
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
Measure Participants	20
Physical component scores	6.66 (7.452)
Mental component scores	5.62 (8.628)
Physical function	5.94 (6.439)
Role-physical	9.81 (10.376)
Bodily pain	5.50 (6.681)
General health	3.53 (6.666)
Vitality	8.29 (8.666)
Social functions	7.91 (8.573)
Role-emotional	6.23 (11.287)
Mental health	4.13 (7.766)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Adverse events were solicited from all subjects at each visit.
Arm/Group Title	Autologous CD34 Cells
Arm/Group Description	Open label active treatment arm. Subjects receive autologous CD34 cells. CLBS16: GCSF-mobilized autologous CD34 cells
All Cause Mortality
	Autologous CD34 Cells
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Autologous CD34 Cells
	Affected / at Risk (%)	# Events
Total	6/20 (30%)
Cardiac disorders
Acute coronary syndrome	1/20 (5%)
Angina pectoris	1/20 (5%)
Hepatobiliary disorders
Hepatitis acute	1/20 (5%)
Injury, poisoning and procedural complications
Coronary artery dissection	1/20 (5%)
Ventricular fibrillation	1/20 (5%)
Vascular pseudoaneurysm	1/20 (5%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/20 (5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma	1/20 (5%)
Nervous system disorders
Dizziness	1/20 (5%)
Syncope	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Autologous CD34 Cells
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Cardiac disorders
Angina pectoris	6/20 (30%)
Gastrointestinal disorders
Nausea	9/20 (45%)
Paraesthesia oral	4/20 (20%)
General disorders
Pain	6/20 (30%)
Pyrexia	2/20 (10%)
Hepatobiliary disorders
Hepatic enzyme increased	3/20 (15%)
Injury, poisoning and procedural complications
Catheter site pain	3/20 (15%)
Musculoskeletal and connective tissue disorders
Bone Pain	11/20 (55%)
Back pain	2/20 (10%)
Fatigue	2/20 (10%)
Nervous system disorders
Headache	6/20 (30%)
Dizziness	5/20 (25%)
Paraesthesia	3/20 (15%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/20 (20%)
Oropharyngeal pain	4/20 (20%)
Upper respiratory tract infection	3/20 (15%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.