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

Phase 2

Completed

• Conditions: Critical Limb Ischemia; Buerger Disease; Thromboangiitis Obliterans; Atherosclerosis Obliterans
• Interventions: Biological: CLBS12; Drug: SOC

• Registration Number: NCT02501018
• Lead Sponsor: Lisata Therapeutics, Inc.

Brief Summary

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).

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 Timeline

• Study First Submitted: 2015-07-14
• Study First Submitted QC: 2015-07-15
• Study First Posted: 2015-07-17
• Study Start: 2017-11-01
• Primary Completion: 2022-05-19
• Study Completion: 2022-05-19
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

• subject has CLI caused by ASO or BD

Exclusion Criteria

• < 20 years old

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CLI Due to ASO with CLBS12 + SOC	CLBS12	This group of subjects with CLI due to ASO will be administered with CLBS12 + SOC for collecting efficacy and safety data.
CLI Due to ASO with CLBS12 + SOC	SOC	This group of subjects with CLI due to ASO will be administered with CLBS12 + SOC for collecting efficacy and safety data.
CLI Due to ASO with SOC	SOC	This group of subjects with CLI due to ASO will be administered with SOC only.
CLI Due to BD with CLBS12	CLBS12	CLBS12 will be administered to patients with CLI due to BD for collecting safety and efficacy data.
CLI Due to BD with CLBS12	SOC	CLBS12 will be administered to patients with CLI due to BD for collecting safety and efficacy data.

Primary Outcome Measures

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

Trial Locations

Locations (12)

Oita Oka Hospital; 🇯🇵 Oita, Japan

Asahikawa Medical University Hospital - 1-1-1 Higashi-2jou; 🇯🇵 Midorigaoka, Asahikawa-shi, Japan

Shonan Kamakura General Hospital; 🇯🇵 Kamakura, Japan

Fukuoka Sanno Hospital; 🇯🇵 Fukuoka, Japan

Kobe City Medical Center General Hospital; 🇯🇵 Kobe, Japan

Shinsuma General Hospital; 🇯🇵 Kobe, Japan

Nippon Medical School Hospital; 🇯🇵 Tokyo, Japan

Tokyo Medical University Hospital; 🇯🇵 Tokyo, Japan

Keio University Hospital; 🇯🇵 Tokyo, Japan

Osaka Saiseikai Nakatsu Hospital; 🇯🇵 Osaka, Japan

Toho University Medical Center Ohashi Hospital; 🇯🇵 Tokyo, Japan

Tokyo Women's Medical University; 🇯🇵 Tokyo, Japan