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

Phase 2

Completed

• Conditions: Diabetes Mellitus
• Interventions: Biological: CLBS03 Low Dose; Biological: CLBS03 High Dose; Biological: Placebo

• Registration Number: NCT02691247
• Lead Sponsor: Lisata Therapeutics, Inc.

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 available

Study Timeline

• Study Start: 2016-02
• Study First Submitted: 2016-02-12
• Study First Submitted QC: 2016-02-20
• Study First Posted: 2016-02-25
• Primary Completion: 2019-03
• Study Completion: 2020-01
• Results First Submitted: 2020-11-18
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-14
• Last Update Submitted: 2020-12-14
• Results First Posted: 2021-01-08
• Last Update Posted: 2021-01-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 113

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
CLBS03 Low Dose	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.
CLBS03 High Dose	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.
Placebo	Placebo	A single infusion of placebo, consisting of the infusion solution only

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Change From Baseline in Mean Daily Dose of Insulin	Week 104
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.
Change in Hemoglobin A1c (HbA1c)	Week 104

Trial Locations

Locations (14)

University of Miami, Diabetes Research Institute; 🇺🇸 Miami, Florida, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Oregon Health Science University; 🇺🇸 Portland, Oregon, United States

Baylor College of Medicine / Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Barbara Davis Center for Diabetes; 🇺🇸 Aurora, Colorado, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Children's Mercy Kansas City; 🇺🇸 Kansas City, Missouri, United States

Vanderbilt Eskind Diabetes Clinic; 🇺🇸 Nashville, Tennessee, United States

Sanford Research; 🇺🇸 Sioux Falls, South Dakota, United States

Joslin Diabetes Center; 🇺🇸 Boston, Massachusetts, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States