Study to Assess the Efficacy and Safety of CLBS12 in Patients With Critical Limb Ischemia (CLI)

A Prospective, Open Label, Controlled, Randomized, Multicenter Study to Assess the Efficacy and Safety of CLBS12 in Patients With Critical Limb Ischemia (CLI) Due to Arteriosclerosis Obliterans (ASO) With a Single-arm Substudy to Assess the Safety and Potential Efficacy of CLBS12 in Patients With CLI Due to Buerger's Disease (BD)

A prospective, open label, controlled, randomized, double arm, multi-center study to assess the efficacy and safety of CLBS12 in patients with critical limb ischemia (CLI) due to arteriosclerosis obliterans (ASO) with a single arm sub-study to assess the safety and potential efficacy of CLBS12 in patients with CLI due to Buerger's Disease (BD).

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia; Thromboangiitis Obliterans; Buerger Disease; Atherosclerosis Obliterans
• Intervention / Treatment: Biological: CLBS12; Drug: SOC

Detailed Description

Main ASO Study: This study will compare safety and efficacy of intramuscular transplantation of autologous CD34+ cells (CLBS12) plus standard of care (SOC) pharmacotherapy (cell treatment arm) versus SOC pharmacotherapy alone (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids) (control arm) in subjects with CLI categorized as Rutherford score 4 or 5 due to ASO aged 20 to 85 years and with no endovascular or surgical revascularization options. Subjects assigned to the cell treatment arm will continue SOC pharmacotherapy and will also receive subcutaneous injections of GRAN® 5 ug/kg/day for 5 days and undergo apheresis on the last day of GRAN® administration. Then each subject in the cell treatment arm will receive intramuscular injections of autologous CD34+ cells. Subjects assigned to the control arm will continue to receive SOC pharmacotherapy alone with the possibility of receiving cell treatment via the rescue option.

BD Substudy: A single arm substudy is included to assess the safety and efficacy of intramuscular transplantation of CLBS12 in patients (N=~5) with CLI categorized as 4 or 5 Rutherford score due to BD aged 20 to 85 years. Subjects who give informed consent will be screened for eligibility within 28 days before registration. Subjects will continue SOC pharmacotherapy and will also receive subcutaneous injections of GRAN® 5 µg/kg/day for 5 days (Pretreatment Days 1 5) to mobilize CD34+ cells into the peripheral blood and undergo apheresis on pretreatment Day 5 to collect CD34+ cells. The choice of pharmacotherapy will be made by the investigators.

Each subject in a cell treatment arm will receive intramuscular injections of up to 1 × 10^6 autologous CD34+ cells/kg/limb. All subjects will be evaluated for efficacy and safety assessments during approximately 12 months.

Efficacy assessments include CLI free status, AFS, PFS, ABI, TBI, SPP, TcPO2, ICD, VAS, and AQA.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Fukuoka Sanno Hospital
  • Kamakura, Japan
    • Shonan Kamakura General Hospital
  • Kobe, Japan
    • Kobe City Medical Center General Hospital
  • Kobe, Japan
    • Shinsuma General Hospital
  • Oita, Japan
    • Oita Oka Hospital
  • Osaka, Japan
    • Osaka Saiseikai Nakatsu Hospital
  • Tokyo, Japan
    • Keio University Hospital
  • Tokyo, Japan
    • Tokyo Medical University Hospital
  • Tokyo, Japan
    • Tokyo Women's Medical University
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
  • Tokyo, Japan
    • Toho University Medical Center Ohashi Hospital
  • Asahikawa-shi
    • Midorigaoka, Asahikawa-shi, Japan, 078-8510
      • Asahikawa Medical University Hospital - 1-1-1 Higashi-2jou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• subject has CLI caused by ASO or BD

Exclusion Criteria:

• < 20 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLI Due to ASO with CLBS12 + SOC; This group of subjects with CLI due to ASO will be administered with CLBS12 + SOC for collecting efficacy and safety data.	Biological: CLBS12; Intramuscular transfusion of CLBS12.; Other Names: CD34+ cells; Drug: SOC; Standard of care (SOC) is defined as pharmacotherapy with approved drugs (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids).; Other Names: Standard of care
Active Comparator: CLI Due to ASO with SOC; This group of subjects with CLI due to ASO will be administered with SOC only.	Drug: SOC; Standard of care (SOC) is defined as pharmacotherapy with approved drugs (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids).; Other Names: Standard of care
Experimental: CLI Due to BD with CLBS12; CLBS12 will be administered to patients with CLI due to BD for collecting safety and efficacy data.	Biological: CLBS12; Intramuscular transfusion of CLBS12.; Other Names: CD34+ cells; Drug: SOC; Standard of care (SOC) is defined as pharmacotherapy with approved drugs (e.g., antiplatelets, anticoagulants, and vasodilators including prostanoids).; Other Names: Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to continuous CLI-free status	CLI-free is determined by assessing the Rutherford score (</=3) by the investigator and a central adjudication committee.	1 year

Collaborators and Investigators

• Sponsor: Lisata Therapeutics, Inc.
• Investigators: Study Director: Kristen K Buck, MD, Lisata Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: July 14, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (Estimate): July 17, 2015

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: CLI, ASO, TAO
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vasculitis; Ischemia; Atherosclerosis; Thromboangiitis Obliterans
• Other Study ID Numbers: CLBS12-P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No