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

• ClinicalTrials.gov Identifier: NCT02691247
• Recruitment Status: Completed
• First Posted: February 25, 2016
• Results First Posted: January 8, 2021
• Last Update Posted: January 8, 2021
• Sponsor: Caladrius Biosciences, Inc.
• Collaborators: Sanford Health; California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Caladrius Biosciences, Inc.

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 (Clinical Trial)
• 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: February 2016
• Actual Primary Completion Date: March 2019
• Actual Study Completion Date: January 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Week 104 ]
3. Change From Baseline in Mean Daily Dose of Insulin [ Time Frame: Week 104 ]

Eligibility Criteria

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

Criteria

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

United States, California

Rady Children's Hospital

San Diego, California, United States, 92123

University of California, San Francisco

San Francisco, California, United States, 94143

United States, Colorado

Barbara Davis Center for Diabetes

Aurora, Colorado, United States, 80045

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06519

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

University of Miami, Diabetes Research Institute

Miami, Florida, United States, 33136

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

Joslin Diabetes Center

Boston, Massachusetts, United States, 02215

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Children's Mercy Kansas City

Kansas City, Missouri, United States, 64108

United States, North Dakota

Sanford Research

Fargo, North Dakota, United States, 58122

United States, Oregon

Oregon Health Science University

Portland, Oregon, United States, 97239

United States, South Dakota

Sanford Research

Sioux Falls, South Dakota, United States, 57104

United States, Tennessee

Vanderbilt Eskind Diabetes Clinic

Nashville, Tennessee, United States, 37232

United States, Texas

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)

Documents provided by Caladrius Biosciences, Inc.:

Study Protocol  [PDF] January 17, 2017

Statistical Analysis Plan  [PDF] January 25, 2019

More Information

• Responsible Party: Caladrius Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT02691247
• Other Study ID Numbers: CLBS03-P01
• First Posted: February 25, 2016
• Results First Posted: January 8, 2021
• Last Update Posted: January 8, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• 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; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases