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

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)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Biological: Placebo; Biological: CLBS03 Low Dose; Biological: CLBS03 High Dose

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Diabetes
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Diabetes Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Kansas City
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Research
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Research
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Eskind Diabetes Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine / Texas Children's Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at 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.	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at 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.	Week 104
Change in Hemoglobin A1c (HbA1c)		Week 104
Change From Baseline in Mean Daily Dose of Insulin		Week 104

Collaborators and Investigators

• Sponsor: Lisata Therapeutics, Inc.
• Collaborators: California Institute for Regenerative Medicine (CIRM); Sanford Health
• Investigators: Study Director: Douglas Losordo, MD, Caladrius Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: February 20, 2016
• First Posted (Estimate): February 25, 2016

Study Record Updates

• Last Update Posted (Actual): January 8, 2021
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Immunotherapy; Type 1 Diabetes Mellitus; Cell therapy; T1DM; T regulatory cell; T-Reg
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CLBS03-P01

Plan for Individual participant data (IPD)

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