Phase 2 Product Candidate for Recent-Onset Type I Diabetes

Caladrius is developing a T-regulatory (Treg) cell-based therapy (CLBS03) for the treatment of type 1 diabetes mellitus (T1DM), using the patient’s own Tregs. At the time of T1DM diagnosis, it is thought that 20% to 30% of the patient’s insulin-producing beta cells remain viable and, if protected from immune destruction, can be salvaged, thus making it possible for the patient to regain glycemic control and to decrease long-term risks of related complications1. Restoration of beta cells' viability and function can also potentially improve the T1DM patient’s quality of life by decreasing the patient’s dependence on exogenous insulin injections and risk for major hypoglycemia and long term micro- and macrovascular complications.

A Phase 1 open-label uncontrolled dose-escalating study conducted at the University of California, San Francisco, and Yale2 provided evidence for the safety and tolerability of autologous expanded polyclonal Treg cell therapy in 14 adults with established T1DM. Infused Tregs were detected in peripheral circulation for more than 12 months, indicating sustainability post administration. In addition, an open-label Phase 1 controlled study of autologous expanded polyclonal Treg cell therapy in 22 children aged 5-18 with new onset T1DM3 similarly demonstrated safety and tolerability while providing evidence of potential bioactivity, as fasting C-peptide level (an indicator of beta cell function) was maintained, and increased rates of remission and insulin independence were observed in the Treg treatment group. Based on these findings, Caladrius received FDA agreement for, and is now conducting, a randomized, double-blind, placebo-controlled Phase 2 study to further investigate the CLBS03 therapy in adolescents with recent-onset T1DM. The FDA also granted CLBS03 Fast Track and Orphan Drug designation for the treatment of type one diabetes in patients with residual beta cell function, making it the first known therapeutic candidate for treatment of T1DM to receive the Fast Track designation. In addition to these designations in the US, the European Medicines Agency granted CLBS03 Advanced Therapeutic Medicinal Product (ATMP) classification. These designations provide numerous development benefits and expedite the process toward the goal of commercialization.

The Sanford Project: T-Rex Study Phase 2 in adolescents with recent onset T1D

Rigorous Design
  • Double-blind, placebo-controlled, randomized (1:1:1) trial
  • Adolescent patients ages 8 to <18 with recent-onset (diagnosed within last 100 days) T1D
Standard Endpoints
  • Preservation of C-peptide level, insulin use, severe hypoglycemic episodes, glucose and hemoglobin A1c levels
Study Size
  • Approximately 111 patients enrolled across ~12 study sites in the USA
  • 80% power to detect a 0.2 pmol/mL difference in AUC mean C-peptide between active and placebo
Study Execution
  • Strategic collaboration with Sanford Research providing operational resources and capital
  • Single infusion of CLBS03 (dose cohorts of 2.5 or 20 million cells/kg) or placebo infusion (control)
For more information, please visit the trial at

The Sanford Project: T-Rex Study Executive Steering Committee

  1. Lernmark Å. (2013) Depleting t cells in newly diagnosed autoimmune (type 1) diabetes—are we getting anywhere? Diabetes, 62:3669-3670.
  2. Bluestone, J., et al. (2015) Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Science Translational Medicine, 7 (315).
  3. Marek-Trzonkowsa, N., et al. (2014) Therapy of type 1 diabetes with CD4(+)CD25(high)CD127-regulatory T cells prolongs survival of pancreatic islets - results of one year follow-up. Clin Immunol., 7 (315): 315ra189.