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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Biological: CLBS03 Low Dose
* Biological: CLBS03 High Dose
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLBS03 Low Dose<br>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<br> <br> |
| Experimental: CLBS03 High Dose<br>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<br> <br> |
| Placebo Comparator: Placebo<br>A single infusion of placebo, consisting of the infusion solution only | Biological: Placebo<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1DM, Type 1 Diabetes Mellitus, T regulatory cell, Immunotherapy, Cell therapy, T-Reg