Efficacy and Safety of Stempeucel® in Patients With Critical Limb Ischemia (CLI) Due to Peripheral Arterial Disease

Title: An Observational, Practice-Based, Open Label, Feasibility Study to Observe the Efficacy and Safety of Intramuscular Administration of Stempeucel® in Malaysian Patients with Critical Limb Ischemia (CLI) Due to Peripheral Arterial Disease

Study Design: Single arm, practice-based, feasibility study

Study Duration: Estimated duration for the main protocol (e.g. from starts of screening to last subject processed and end of the study) is approximately 18 months

Study Center: Universiti Kebangsaan Malaysia Medical Centre (UKMMMC), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Wilayah Persekutuan, Malaysia

Objectives: To observe the efficacy and safety of Stempeucel® (adult human bone marrow derived, cultured, pooled, allogeneic mesenchymal stromal cells) in Malaysian patients with critical limb ischemia (CLI) due to peripheral arterial disease.

Investigational Medicinal Product

Description

• Ex-vivo cultured allogeneic mesenchymal stem cells (MSCs) supplied in cryo-bags consisting of 150 or 200 million, suspended in 50 ml of Plasmalyte A containing 1.5% human serum albumin (HSA) and 3% dimethyl sulfoxide (DMSO).

Dosage • Dosing of Stempeucel® is based on body weight. The recommended dose is 2 million cells/kg body weight.

Administration

• 40 - 60 injections administered as 0.6 ml/kg (200 million bag) or 0.8 ml/kg (150 million bag) intramuscularly into different points on the muscle. Additional injections of 2 ml (200 million bag) or 3 ml (150 million bag) administered around the ulcer

Number of Subjects: 10 patients

Data Analysis

Data Management:

• Electronic case record form (eCRF) will be used for data entry.
• Oracle clinical (or other suitable alternatives with audit trail) will be used for data management.

Statistical Method:

• The SPSS® package (IBM Inc., USA, version 22) will be used for statistical evaluation.
• All patients in the study with relevant efficacy and safety data will be considered for the analysis.
• Efficacy analysis will be done using GEE (Generalized Estimating Equations) method or paired t test as appropriate.
• Adverse events monitored using information voluntarily disclosed by the patients and as observed by the PI will be summarized descriptively by total number of AE(s).
• AEs will be categorized as: all AEs, all treatment-emergent AEs, all severe AEs, treatment-related AEs and severe treatment-related AEs. These events will be reported as appropriate and summarized.

Inclusion criteria

• Patients between 18-65 years old
• Patients diagnosed with atherosclerotic peripheral arterial disease
• Patients not eligible for or have failed surgical or percutaneous revascularization (No option patients)
• Patients with at least one ulcer (between 0.5 to 10 cm2 size)
• Ankle brachial pressure index (ABPI) ≤ 0.6 (toe brachial index (TBI) if ABPI out of range; TBI ≤ 0.5)
• Patients who are able and willing to provide consent and agrees to comply with study procedures and follow-up evaluations

Exclusion criteria

• Patients diagnosed with Buerger's disease by Shionoya criteria
• Patients eligible for surgical or percutaneous revascularization
• Patients with a history of participating in another stem cell trial or therapy within 3 months
• Patients who are unsuitable to participate the clinical trial as determined by investigators