Clinical trial NCT05854615: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Critical Limb Ischemia
Buerger's Disease
Keywords: critical limb ischemia
Buerger's disease
bone marrow derived mesenchymal stem cell
Lead sponsor: Cell Biopeutics Resources Sdn Bhd
Sponsor class: INDUSTRY
Collaborators: name: Stempeutics Research Pvt Ltd
name: National University of Malaysia
First posted: 2023-05-11
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

Eligibility criteria: Inclusion Criteria:

1. Males or females (willing to use accepted methods of contraception during the course of the study) in the age group of 18-65 years.
2. Buerger's disease as diagnosed by Shionoya criteria
3. Patients should have at least one ulcer (target ulcer): area between 0.5 to 10 cm2 (both inclusive)
4. 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
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:

1. Patients diagnosed with atherosclerotic peripheral arterial disease
2. Patients eligible for surgical or percutaneous revascularization
3. Patients with a history of participating in another stem cell trial or therapy within 3 months
4. Patients who are unsuitable to participate the clinical trial as determined by investigators

Primary outcomes:
measure: Change in ischemic rest pain
timeFrame: Screening (Day -14 to -1), Day 30, 90, 180 and 360
measure: Change in size of the ulcer
timeFrame: Screening (Day -14 to -1), Day 30, 90, 180 and 360
measure: Change in ankle brachial pressure index (ABPI)
timeFrame: Screening (Day -14 to -1), Day 30, 90, 180 and 360
measure: Change in total walking distance
timeFrame: Screening (Day -14 to -1), Day 30, 90, 180 and 360
measure: Change in major amputation-free survival
timeFrame: Screening (Day -14 to -1), Day 30, 90, 180 and 360
measure: Change in angiogenesis
timeFrame: Screening (Day -14 to -1), Day 180
Secondary outcomes:
measure: The type of AE(s), number of AE(s) and proportion of patients with AE(s)
timeFrame: Screening (Day -14 to -1)
measure: Incidence of abnormal laboratory test results (serum chemistry, haematology, liver function test)
timeFrame: Screening (Day -14 to -1), Day 7, 30, 90, 180 and 360
measure: Incidence of abnormal urine test results
timeFrame: Screening (Day -14 to -1), Day 180
measure: Incidence of abnormal TNF-α
timeFrame: Screening (Day -14 to -1), Day 7 and 30
measure: Incidence of abnormal vital signs
timeFrame: Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360
measure: Incidence of abnormal physical examination
timeFrame: Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360
measure: Incidence of abnormal ECG parameters
timeFrame: Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360
measure: Incidence of abnormal chest condition
timeFrame: Screening (Day -14 to -1), Day 180
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: Hospital Canselor Tunku Mukhriz
Study officials:
affiliation: National University of Malaysia
name: Hanafiah Harunarashid, MS
role: PRINCIPAL_INVESTIGATOR
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