Critical Limb Ischemia, Peripheral Arterial Disease
Conditions
Keywords
critical limb ischemia, peripheral arterial disease, bone marrow-derived mesenchymal stem cell
Brief summary
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.
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 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.
Interventions
BIOLOGICALStempeucel®
• 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).
Sponsors
Stempeutics Research Pvt Ltd
National University of Malaysia
Cell Biopeutics Resources Sdn Bhd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ischemic rest pain | Screening (Day -14 to -1), Day 30, 90, 180 and 360 | Change in visual analog score (VAS) compared to screening |
| Change in size of the ulcer | Screening (Day -14 to -1), Day 30, 90, 180 and 360 | Change in size of the ulcer compared to screening |
| Change in ankle brachial pressure index (ABPI) | Screening (Day -14 to -1), Day 30, 90, 180 and 360 | Change in ankle brachial pressure index (ABPI) compared to screening |
| Change in total walking distance | Screening (Day -14 to -1), Day 30, 90, 180 and 360 | Change in total walking distance on a treadmill compared to screening |
| Change in major amputation-free survival | Screening (Day -14 to -1), Day 30, 90, 180 and 360 | Change in amputation-free survival compared to screening |
| Change in angiogenesis | Screening (Day -14 to -1), Day 180 | Change in angiogenesis measured by digital subtraction angiogram (DSA) compared to screening |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of abnormal ECG parameters | Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360 | The following assessments will be conducted: 12 lead ECG recordings with long Lead II, and two-dimensional echocardiography (2D ECHO; if needed). In case of abnormal conditions, they shall be recorded as an adverse event or excluded from study (screening). |
| The type of AE(s), number of AE(s) and proportion of patients with AE(s) | Screening (Day -14 to -1) | Monitored and recorded as voluntarily disclosed by the patients and as observed by the Investigator throughout the study |
| Incidence of abnormal chest condition | Screening (Day -14 to -1), Day 180 | Chest x-ray will be conducted. In case of abnormal conditions, they shall be recorded as an adverse event or excluded from study (screening). |
| Incidence of abnormal laboratory test results (serum chemistry, haematology, liver function test) | Screening (Day -14 to -1), Day 7, 30, 90, 180 and 360 | The following lab tests will be conducted: serum chemistry, haematology, liver function test. In case of abnormal results, they shall be recorded as an adverse event or excluded from study (screening). |
| Incidence of abnormal urine test results | Screening (Day -14 to -1), Day 180 | Urine test will be conducted. In case of abnormal results, they shall be recorded as an adverse event or excluded from study (screening). |
| Incidence of abnormal TNF-α | Screening (Day -14 to -1), Day 7 and 30 | TNF-α test will be conducted. In case of abnormal results, they shall be recorded as an adverse event or excluded from study (screening). |
| Incidence of abnormal vital signs | Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360 | The following assessments will be conducted: blood pressure, heart rate, respiratory rate and temperature. In case of abnormal results, they shall be recorded as an adverse event or excluded from the study (screening). |
| Incidence of abnormal physical examination | Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360 | The following examinations will be conducted: visual, heart, lungs, abdomen, nervous system, muscoskeletal system and etc. In case of abnormal conditions, they shall be recorded as an adverse event or excluded from the study (screening). |
Countries
Malaysia
Contacts
Primary ContactJezamine Lim, PhD
Outcome results
None listed