Efficacy and Safety of Stempeucel® in Patients With Critical Limb Ischemia (CLI) Due to Buerger's Disease

Official 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 Buerger's Disease

Overview

The goal of this observational, practice-based feasibility study is to observe the efficacy and safety of intramuscular administration of Stempeucel® in Malaysian patients with critical limb ischemia (CLI) due to Buerger's disease. The main questions it aims to answer are: * Can intramuscular administration of Stempeucel® reduce symptoms of CLI due to Buerger's disease while improving the healing rate and functional outcomes? * Does intramuscular administration of Stempeucel® causes any serious adverse events in CLI due to Buerger's disease patients? Study patients will be assessed by the PI before administering the Stempeucel® for any other organ with inflammation. The study patients will also be followed up to the duration of 1 year after study treatment administration for safety and efficacy assessment.

Detailed description

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 Buerger's 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 Buerger's 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 3 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.

Interventions

• Biological Adult human bone marrow derived, cultured, pooled, allogeneic mesenchymal stromal cells
  • 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).

Primary outcome measures

• Change in ischemic rest pain [Time frame: Screening (Day -14 to -1), Day 30, 90, 180 and 360]
• Change in size of the ulcer [Time frame: Screening (Day -14 to -1), Day 30, 90, 180 and 360]
• Change in ankle brachial pressure index (ABPI) [Time frame: Screening (Day -14 to -1), Day 30, 90, 180 and 360]
• Change in total walking distance [Time frame: Screening (Day -14 to -1), Day 30, 90, 180 and 360]
• Change in major amputation-free survival [Time frame: Screening (Day -14 to -1), Day 30, 90, 180 and 360]
• Change in angiogenesis [Time frame: Screening (Day -14 to -1), Day 180]

Secondary outcome measures (8)

• The type of AE(s), number of AE(s) and proportion of patients with AE(s) [Time frame: Screening (Day -14 to -1)]
• Incidence of abnormal laboratory test results (serum chemistry, haematology, liver function test) [Time frame: Screening (Day -14 to -1), Day 7, 30, 90, 180 and 360]
• Incidence of abnormal urine test results [Time frame: Screening (Day -14 to -1), Day 180]
• Incidence of abnormal TNF-α [Time frame: Screening (Day -14 to -1), Day 7 and 30]
• Incidence of abnormal vital signs [Time frame: Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360]
• Incidence of abnormal physical examination [Time frame: Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360]
• Incidence of abnormal ECG parameters [Time frame: Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360]
• Incidence of abnormal chest condition [Time frame: Screening (Day -14 to -1), Day 180]

Eligibility criteria

Inclusion criteria

• Males or females (willing to use accepted methods of contraception during the course of the study) in the age group of 18-65 years.
• Buerger's disease as diagnosed by Shionoya criteria
• Patients should have at least one ulcer (target ulcer): area between 0.5 to 10 cm2 (both inclusive)
• Ankle Brachial Pressure Index (ABPI) ≤ 0.6. If ABPI is ≥ 1.1 then Toe Brachial Index (TBI) will be performed and TBI should be ≤ 0.5
• Patients who are able to understand the requirements of the study, and willing to provide voluntary written informed consent, abide by the study requirements, and agree to return for required follow-up visits

Exclusion criteria

• Patients diagnosed with atherosclerotic peripheral arterial disease
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Malaysia · 1 center

• Hospital Canselor Tunku Mukhriz — Kuala Lumpur

Publications

• Haugen S, Casserly IP, Regensteiner JG, Hiatt WR. Risk assessment in the patient with established peripheral arterial disease. Vasc Med. 2007 Nov;12(4):343-50. doi: 10.1177/1358863X07083278. PMID 18048472
• Sprengers RW, Lips DJ, Moll FL, Verhaar MC. Progenitor cell therapy in patients with critical limb ischemia without surgical options. Ann Surg. 2008 Mar;247(3):411-20. doi: 10.1097/SLA.0b013e318153fdcb. PMID 18376183
• Dormandy J, Heeck L, Vig S. The fate of patients with critical leg ischemia. Semin Vasc Surg. 1999 Jun;12(2):142-7. PMID 10777241
• Gottsater A. Managing risk factors for atherosclerosis in critical limb ischaemia. Eur J Vasc Endovasc Surg. 2006 Nov;32(5):478-83. doi: 10.1016/j.ejvs.2006.03.007. Epub 2006 Apr 24. PMID 16631394
• Schiavetta A, Maione C, Botti C, Marino G, Lillo S, Garrone A, Lanza L, Pagliari S, Silvestroni A, Signoriello G, Sica V, Cobellis G. A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the Naples and Pietra Ligure Evaluation of Stem Cells study. Stem Cells Transl Med. 2012 Jul;1(7):572-8. doi: 10.5966/sctm.2012-0021. Epub 2012 Jul 6. PMID 23197862
• Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis. 2010 Mar;209(1):10-7. doi: 10.1016/j.atherosclerosis.2009.08.033. Epub 2009 Aug 21. PMID 19740466
• Conte MS, Geraghty PJ, Bradbury AW, Hevelone ND, Lipsitz SR, Moneta GL, Nehler MR, Powell RJ, Sidawy AN. Suggested objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc Surg. 2009 Dec;50(6):1462-73.e1-3. doi: 10.1016/j.jvs.2009.09.044. Epub 2009 Nov 7. PMID 19897335
• Marston WA, Davies SW, Armstrong B, Farber MA, Mendes RC, Fulton JJ, Keagy BA. Natural history of limbs with arterial insufficiency and chronic ulceration treated without revascularization. J Vasc Surg. 2006 Jul;44(1):108-114. doi: 10.1016/j.jvs.2006.03.026. PMID 16828434

Identifiers

NCT: NCT05854615 · CBR-BD-22-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗