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.

Tracking Information

• First Submitted Date: February 12, 2016
• First Posted Date: February 25, 2016
• Results First Submitted Date: November 18, 2020
• Results First Posted Date: January 8, 2021
• Last Update Posted Date: January 8, 2021
• Actual Study Start Date: February 2016
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 14, 2020)

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.

• Original Primary Outcome Measures (submitted: February 20, 2016): Mixed Meal Tolerance Test (MMTT)-stimulated C-peptide area under the curve (AUC) [ Time Frame: Week 52 ]

Current Secondary Outcome Measures (submitted: December 14, 2020)

• 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.
• Change in Hemoglobin A1c (HbA1c) [ Time Frame: Week 104 ]
• Change From Baseline in Mean Daily Dose of Insulin [ Time Frame: Week 104 ]

Original Secondary Outcome Measures (submitted: February 20, 2016)

• MMTT-stimulated C-peptide AUC [ Time Frame: Week 104 ]
• Change in Hemoglobin A1c (HbA1c) [ Time Frame: Week 104 ]
• Change in insulin usage [ Time Frame: Week 104 ]
• Proportion of subjects with adverse events [ Time Frame: Week 104 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of CLBS03 in Adolescents With Recent Onset Type 1 Diabetes (The Sanford Project T-Rex Study)
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Diabetes Mellitus

Intervention

• Biological: CLBS03 Low Dose
• Biological: CLBS03 High Dose
• Biological: Placebo

Study Arms

• 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.
  Intervention: 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.
  Intervention: Biological: CLBS03 High Dose
• Placebo Comparator: Placebo
  A single infusion of placebo, consisting of the infusion solution only
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 10, 2018): 113
• Original Estimated Enrollment (submitted: February 20, 2016): 111
• Actual Study Completion Date: January 2020
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02691247
• Other Study ID Numbers: CLBS03-P01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Caladrius Biosciences, Inc.
• Study Sponsor: Caladrius Biosciences, Inc.

Collaborators

• Sanford Health
• California Institute for Regenerative Medicine (CIRM)

Investigators

• Study Director: Douglas Losordo, MD; Caladrius Biosciences

• PRS Account: Caladrius Biosciences, Inc.
• Verification Date: December 2020