CLBS12

Product Candidate for Critical Limb Ischemia

Caladrius plans to develop its product candidate, CLBS12, in Japan under Japan’s regenerative medicine law only with a partner.  This law enables an expedited path to conditional approval for regenerative medicine products that show sufficient safety evidence and signals of efficacy in a phase 2 study. The program is supported by three previous independent studies of autologous CD34 cells in no-option CLI patients. Caladrius has recently completed consultations with the Japanese regulatory authorities on a Phase 2 CLI protocol.

No-Option Critical Limb Ischemia

  • If options for surgical or endovascular therapies are exhausted, patients only receive pain management, wound care or amputation
  • Even with surgical options over 50% lead to amputation or death within one year*
  • Prevalence (Japan): 21K CLI no-option patients**
  • Incidence (Japan): ~2K – 8K per year***

* TASC II Guidelines, Huron Primary Research (Sept-Oct/2014)
** Norgren et al. (2007) J Vasc Surg; Varu et al. (2010) J Vasc Surg; Globaldata
*** Source: Nihon GekaGakkaiZasshi. 2007 Jul;108(4):171-5, Am FamPhysician. 1999 Apr 1;59(7):1899-1908; TASC II Guidelines, Huron Primary Research (Sept-Oct/2014)

CLBS12 CLI Japan Program Background

Previous studies of autologous CD34+ cells in no-option CLI patients in Japan and U.S. (combined total, N=56)

Conclusions from 2 previous studies in Japan:

  • Study 1: CD34 cell injection was safe and led to improvement in all clinical parameters (Kawamoto A et al. Stem Cells 2009)
  • Study 2: CD34 cell injection was safe and led to improvement in CLI-free status as well as other clinical parameters (Fujita Y et al. Circ J 2014)

Conclusion from previous study in U.S.:

  • CD34 cell injection was safe and led to improved amputation free survival (Losordo et al. Circ Cardiovasc Interv 2012)

Phase 2 study in Japan targeting conditional approval

Study designed in consultation with PMDA

Description

Prospective, open label controlled, randomized, multicenter study in patients with no-option CLI

Dosage

Up to 106 autologous G-CSF-mobilized peripheral blood-derived CD34+ cells/kg per affected limb

Study Size

35 subjects

Primary Endpoint

Time to continuous CLI free status

Dosage Form

Solution/suspension; injectable

Dosage Frequency

Once

Mode of Administration

Intramuscular

Control/Comparator

SOC pharmacotherapy with drugs approved in Japan
(e.g., antiplatelets, anticoagulants, and vasodilators)

The choice of pharmacotherapy will be made by the investigators