Phase 2 Product Candidate for Type I Diabetes
Caladrius is currently focused on developing a T-regulatory (Treg) cell-based therapy (CLBS03, formerly NBS03D) for the treatment of type 1 diabetes mellitus (T1DM), using the patient’s own numerically and functionally enhanced Tregs. At the time of T1DM diagnosis, up to 20% of the patient’s insulin producing beta cells remain in the pancreas, and if protected from immune destruction, can be salvaged, and restored to function, thus regaining glycemic control and decreasing long-term risks of related complications. Restoration of beta cells viability and function can also potentially improve the 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 UCSF and Yale provided evidence for safety and tolerability of autologous expanded polyclonal Treg cell therapy (produced in a comparable way to CLBS03) in 14 adults with established T1DM. Infused Tregs were detected in peripheral circulation for more than 6 months, indicating sustainability post administration. In addition, a Polish Phase 1 open-label controlled study of autologous expanded polyclonal Treg cell therapy in 22 children aged 5-18 with new onset T1DM 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, NeoStem received FDA approval to conduct a randomized, double-blind, placebo-controlled Phase 2 study to further investigate the CLBS03 therapy in adolescents with new onset T1DM.
CLBS03 Phase 2 Study Design
Randomized (1:1), double-blind, placebo controlled trial for T1DM in adolescents
Preservation of C-peptide at 52 weeks in comparison to placebo
80% power to detect 50% attenuation of the decline in mixed meal tolerance test stimulated c-peptide in comparison to placebo, adjusted for baseline
111 patients, ~11 centers in the U.S.
CLBS03: single dose autologous ex-vivo expanded polyclonal Treg cell therapy
2 doses: 10 and 20 million cells/kg
Matching infusion with placebo