NCT02691247

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
113

participants targeted

Target at P50-P75 for phase_2 diabetes-mellitus

Timeline
Completed

Started Feb 2016

Typical duration for phase_2 diabetes-mellitus

Geographic Reach
1 country

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2016

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

February 12, 2016

Completed
13 days until next milestone

First Posted

Study publicly available on registry

February 25, 2016

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2019

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2020

Completed
1 year until next milestone

Results Posted

Study results publicly available

January 8, 2021

Completed
Last Updated

January 8, 2021

Status Verified

December 1, 2020

Enrollment Period

3.1 years

First QC Date

February 12, 2016

Results QC Date

November 18, 2020

Last Update Submit

December 14, 2020

Conditions

Keywords

T1DMType 1 Diabetes MellitusT regulatory cellImmunotherapyCell therapyT-Reg

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104

    Week 104

  • Change in Hemoglobin A1c (HbA1c)

    Week 104

  • Change From Baseline in Mean Daily Dose of Insulin

    Week 104

Study Arms (3)

CLBS03 Low Dose

EXPERIMENTAL

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

CLBS03 High Dose

EXPERIMENTAL

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

PLACEBO COMPARATOR

A single infusion of placebo, consisting of the infusion solution only

Biological: Placebo

Interventions

CLBS03 Low DoseBIOLOGICAL
CLBS03 Low Dose
CLBS03 High Dose
PlaceboBIOLOGICAL
Placebo

Eligibility Criteria

Age8 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami, Diabetes Research Institute

Miami, Florida, 33136, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Kansas City

Kansas City, Missouri, 64108, United States

Location

Sanford Research

Fargo, North Dakota, 58122, United States

Location

Oregon Health Science University

Portland, Oregon, 97239, United States

Location

Sanford Research

Sioux Falls, South Dakota, 57104, United States

Location

Vanderbilt Eskind Diabetes Clinic

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine / Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Bender C, Wiedeman AE, Hu A, Ylescupidez A, Sietsema WK, Herold KC, Griffin KJ, Gitelman SE, Long SA; T-Rex Study Groupdagger; T-Rex Clinical Study Group. A phase 2 randomized trial with autologous polyclonal expanded regulatory T cells in children with new-onset type 1 diabetes. Sci Transl Med. 2024 May 8;16(746):eadn2404. doi: 10.1126/scitranslmed.adn2404. Epub 2024 May 8.

MeSH Terms

Conditions

Diabetes MellitusDiabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
William Sietsema
Organization
Caladrius Biosciences

Study Officials

  • Douglas Losordo, MD

    Caladrius Biosciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 12, 2016

First Posted

February 25, 2016

Study Start

February 1, 2016

Primary Completion

March 1, 2019

Study Completion

January 1, 2020

Last Updated

January 8, 2021

Results First Posted

January 8, 2021

Record last verified: 2020-12

Data Sharing

IPD Sharing
Will not share

Locations