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

Официальное название

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.

Обзор

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 peripheral arterial disease. The main questions it aims to answer are: * Can intramuscular administration of Stempeucel® reduce symptoms of CLI due to peripheral arterial disease while improving the healing rate and functional outcomes? * Does intramuscular administration of Stempeucel® causes any serious adverse events in CLI due to peripheral arterial 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.

Подробное описание

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.

Вмешательства

• Биопрепарат Stempeucel®
  • 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).

Первичные конечные точки

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

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Малайзия · 1 центр

• Hospital Canselor Tunku Mukhriz — Kuala Lumpur

Публикации

• 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
• 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
• 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

Идентификаторы

NCT: NCT05854641 · CBR-PAD-22-004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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