Safety and Efficacy of CLBS03 in Adolescents With Recent Onset Type 1 Diabetes (The Sanford Project T-Rex Study)

• Sponsor: Caladrius Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02691247
• Collaborator: Sanford Health (Other), California Institute for Regenerative Medicine (CIRM) (Other)
• Enrollment: 113
• Locations: 15
• Arms: 3
• Actual Duration (Months): 47
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This clinical trial will explore the safety and effect of autologous ex vivo expanded polyclonal regulatory T-cells on beta cell function in patients, aged 8 to 17, with recent onset T1DM. Other measures of diabetes severity and the autoimmune response underlying T1DM will also be explored. Eligible subjects will receive a single infusion of CLBS03 (high or low dose) or placebo.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Biological: CLBS03 Low Dose; Biological: CLBS03 High Dose; Biological: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 113 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective Randomized Placebo-Controlled Double Blind Clinical Trial to Evaluate the Safety and Efficacy of CLBS03 (Autologous Ex Vivo Expanded Polyclonal Regulatory T-cells) in Adolescents With Recent Onset Type 1 Diabetes Mellitus (T1DM)
• Actual Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CLBS03 Low Dose A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution.	Biological: CLBS03 Low Dose
Experimental: CLBS03 High Dose A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution.	Biological: CLBS03 High Dose
Placebo Comparator: Placebo A single infusion of placebo, consisting of the infusion solution only	Biological: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52 [Week 52]

   The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.

Secondary Outcome Measures

1. Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104 [Week 104]

   The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.

2. Change in Hemoglobin A1c (HbA1c) [Week 104]

3. Change From Baseline in Mean Daily Dose of Insulin [Week 104]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and females aged 8 to 17 years of age

• Diagnosis of T1DM within 100 days of receipt of study drug

• Positive for at least one islet cell autoantibody

• Peak MMTT-stimulated C-peptide level > 0.2 pmol/mL (at the screening visit)

• Weight of ≥30 kg

• Must agree to use a reliable and acceptable method of contraception for the duration of participation

• Willing and medically acceptable to postpone live vaccine immunizations for one year after infusion

• Written informed consent and written assent

Exclusion Criteria:

• Hemoglobin less than the lower limit of normal

• Leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL

• Regulatory T-cells present in peripheral blood at <20 cells per μL

• Current or ongoing use of non-insulin pharmaceuticals (that may affect glycemic control)

• Current or anticipated use of systemic corticosteroids or other immunomodulatory drugs

• Recent serious bacterial, viral, fungal, or other opportunistic infections

• History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease

• Serologic evidence of current or past viral infection: human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, and human T-lymphotropic virus (HTLV) 1/2

• Positive QuantiFERON® tuberculosis (TB) test, purified protein derivative (PPD) skin test, history of tuberculosis, or active TB infection

• Active infection with Epstein-Barr Virus or Cytomegalovirus

• Liver disease

• Pregnant or breast-feeding

• Vaccination with a live virus within 8 weeks of receipt of study drug

• Vaccination with a killed virus within 2 weeks of receipt of study drug

• Participation in an investigational drug study within 90 days prior to screening

• Previously treated with a T-Reg based cell therapy

• History of allergy to gentamicin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rady Children's Hospital	San Diego	California	United States	92123
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Barbara Davis Center for Diabetes	Aurora	Colorado	United States	80045
4	Yale University School of Medicine	New Haven	Connecticut	United States	06519
5	University of Florida	Gainesville	Florida	United States	32610
6	University of Miami, Diabetes Research Institute	Miami	Florida	United States	33136
7	Indiana University	Indianapolis	Indiana	United States	46202
8	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
9	University of Minnesota	Minneapolis	Minnesota	United States	55455
10	Children's Mercy Kansas City	Kansas City	Missouri	United States	64108
11	Sanford Research	Fargo	North Dakota	United States	58122
12	Oregon Health Science University	Portland	Oregon	United States	97239
13	Sanford Research	Sioux Falls	South Dakota	United States	57104
14	Vanderbilt Eskind Diabetes Clinic	Nashville	Tennessee	United States	37232
15	Baylor College of Medicine / Texas Children's Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

• Caladrius Biosciences, Inc.
• Sanford Health
• California Institute for Regenerative Medicine (CIRM)

Investigators

• Study Director: Douglas Losordo, MD, Caladrius Biosciences

Study Documents (Full-Text)

• Study Protocol - Jan 17, 2017
• Statistical Analysis Plan - Jan 25, 2019

More Information

Publications

None provided.

• Responsible Party: Caladrius Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT02691247
• Other Study ID Numbers: CLBS03-P01
• First Posted: Feb 25, 2016
• Last Update Posted: Jan 8, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Caladrius Biosciences, Inc.: T1DM; Type 1 Diabetes Mellitus; T regulatory cell; Immunotherapy; Cell therapy; T-Reg
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1

Study Results

Participant Flow

Arm/Group Title	CLBS03 Low Dose	CLBS03 High Dose	Placebo
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose	A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose	A single infusion of placebo, consisting of the infusion solution only Placebo
Period Title: Overall Study
STARTED	40	24	46
COMPLETED	37	22	43
NOT COMPLETED	3	2	3

Baseline Characteristics

Arm/Group Title	CLBS03 Low Dose	CLBS03 High Dose	Placebo	Total
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose	A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose	A single infusion of placebo, consisting of the infusion solution only Placebo	Total of all reporting groups
Overall Participants	40	24	46	110
Age (Count of Participants)
<=18 years	40 100%	24 100%	46 100%	110 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 25%	5 20.8%	13 28.3%	28 25.5%
Male	30 75%	19 79.2%	33 71.7%	82 74.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 12.5%	2 8.3%	2 4.3%	9 8.2%
Not Hispanic or Latino	34 85%	22 91.7%	44 95.7%	100 90.9%
Unknown or Not Reported	1 2.5%	0 0%	0 0%	1 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.5%	0 0%	0 0%	1 0.9%
Asian	1 2.5%	0 0%	0 0%	1 0.9%
Native Hawaiian or Other Pacific Islander	1 2.5%	1 4.2%	3 6.5%	5 4.5%
Black or African American	1 2.5%	0 0%	1 2.2%	2 1.8%
White	36 90%	23 95.8%	42 91.3%	101 91.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%	24 100%	46 100%	110 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52
Description	The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CLBS03 Low Dose	CLBS03 High Dose	Placebo
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose	A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose	A single infusion of placebo, consisting of the infusion solution only Placebo
Measure Participants	40	24	46
Mean (Standard Deviation) [pmol*hr/mL]	-0.2863 (0.25988)	-0.3895 (0.31425)	-0.2670 (0.25745)

2. Secondary Outcome

Title	Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104
Description	The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CLBS03 Low Dose	CLBS03 High Dose	Placebo
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose	A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose	A single infusion of placebo, consisting of the infusion solution only Placebo
Measure Participants	40	24	46
Mean (Standard Deviation) [pmol*hr/mL]	-0.4492 (0.33135)	-0.5224 (0.33903)	-0.4412 (0.28923)

3. Secondary Outcome

Title	Change in Hemoglobin A1c (HbA1c)
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CLBS03 Low Dose	CLBS03 High Dose	Placebo
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose	A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose	A single infusion of placebo, consisting of the infusion solution only Placebo
Measure Participants	39	24	46
Mean (Standard Deviation) [HbA1c %]	1.56 (1.660)	1.05 (1.474)	1.77 (2.162)

4. Secondary Outcome

Title	Change From Baseline in Mean Daily Dose of Insulin
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CLBS03 Low Dose	CLBS03 High Dose	Placebo
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose	A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose	A single infusion of placebo, consisting of the infusion solution only Placebo
Measure Participants	39	24	46
Mean (Standard Deviation) [U/kg body weight]	0.3840 (0.39727)	0.4619 (0.40220)	0.2874 (0.33602)

Adverse Events

Time Frame	2 years
Arm/Group Title	CLBS03 Low Dose		CLBS03 High Dose		Placebo
Arm/Group Description	A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution. CLBS03 Low Dose		A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution. CLBS03 High Dose		A single infusion of placebo, consisting of the infusion solution only Placebo
All Cause Mortality
	CLBS03 Low Dose		CLBS03 High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/24 (0%)		0/46 (0%)
Serious Adverse Events
	CLBS03 Low Dose		CLBS03 High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/40 (10%)		2/24 (8.3%)		3/46 (6.5%)
Gastrointestinal disorders
Gastritis	1/40 (2.5%)	1	0/24 (0%)	0	0/46 (0%)	0
Infections and infestations
Gastroenteritis viral	1/40 (2.5%)	1	0/24 (0%)	0	0/46 (0%)	0
Groin abscess	0/40 (0%)	0	1/24 (4.2%)	1	0/46 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	3/40 (7.5%)	3	0/24 (0%)	0	2/46 (4.3%)	5
Hyperglycaemia	1/40 (2.5%)	1	0/24 (0%)	0	0/46 (0%)	0
Hypoglycaemia	0/40 (0%)	0	1/24 (4.2%)	1	0/46 (0%)	0
Psychiatric disorders
Major depression	0/40 (0%)	0	0/24 (0%)	0	1/46 (2.2%)	1
Suicidal ideation	0/40 (0%)	0	1/24 (4.2%)	1	1/46 (2.2%)	1
Suicide attempt	0/40 (0%)	0	1/24 (4.2%)	1	0/46 (0%)	0
Other (Not Including Serious) Adverse Events
	CLBS03 Low Dose		CLBS03 High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/40 (95%)		24/24 (100%)		46/46 (100%)
Blood and lymphatic system disorders
Neutropenia	0/40 (0%)		0/24 (0%)		4/46 (8.7%)
Gastrointestinal disorders
Abdominal pain upper	5/40 (12.5%)		3/24 (12.5%)		1/46 (2.2%)
Diarrhoea	3/40 (7.5%)		3/24 (12.5%)		2/46 (4.3%)
Nausea	4/40 (10%)		1/24 (4.2%)		2/46 (4.3%)
Vomiting	5/40 (12.5%)		2/24 (8.3%)		10/46 (21.7%)
General disorders
Influence like illness	2/40 (5%)		2/24 (8.3%)		2/46 (4.3%)
Pyrexia	3/40 (7.5%)		2/24 (8.3%)		3/46 (6.5%)
Immune system disorders
Seasonal allergy	3/40 (7.5%)		0/24 (0%)		2/46 (4.3%)
Infections and infestations
Gastroenteritis	1/40 (2.5%)		0/24 (0%)		3/46 (6.5%)
Gastroenteritis viral	2/40 (5%)		1/24 (4.2%)		5/46 (10.9%)
Influenza	4/40 (10%)		3/24 (12.5%)		4/46 (8.7%)
Nasopharyngitis	7/40 (17.5%)		8/24 (33.3%)		7/46 (15.2%)
Pharyngitis streptococcal	4/40 (10%)		5/24 (20.8%)		2/46 (4.3%)
Upper respiratory tract infection	12/40 (30%)		13/24 (54.2%)		18/46 (39.1%)
Viral infection	3/40 (7.5%)		1/24 (4.2%)		3/46 (6.5%)
Injury, poisoning and procedural complications
Concussion	2/40 (5%)		1/24 (4.2%)		3/46 (6.5%)
Limb injury	3/40 (7.5%)		0/24 (0%)		0/46 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	3/40 (7.5%)		0/24 (0%)		2/46 (4.3%)
Hypoglycaemia	3/40 (7.5%)		1/24 (4.2%)		4/46 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/40 (5%)		0/24 (0%)		3/46 (6.5%)
Back pain	1/40 (2.5%)		2/24 (8.3%)		0/46 (0%)
Pain in extremity	3/40 (7.5%)		0/24 (0%)		3/46 (6.5%)
Nervous system disorders
Headache	8/40 (20%)		5/24 (20.8%)		11/46 (23.9%)
Migraine	0/40 (0%)		2/24 (8.3%)		1/46 (2.2%)
Presyncope	0/40 (0%)		2/24 (8.3%)		1/46 (2.2%)
Somnolence	3/40 (7.5%)		0/24 (0%)		0/46 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	5/40 (12.5%)		4/24 (16.7%)		6/46 (13%)
Epistaxis	3/40 (7.5%)		0/24 (0%)		0/46 (0%)
Nasal congestion	5/40 (12.5%)		4/24 (16.7%)		4/46 (8.7%)
Sinus congestion	1/40 (2.5%)		2/24 (8.3%)		0/46 (0%)
Skin and subcutaneous tissue disorders
Lipohypertrophy	2/40 (5%)		2/24 (8.3%)		4/46 (8.7%)

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.