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

Critical Limb Ischemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05854615
• Other study ID #: CBR-BD-22-003
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2024
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Cell Biopeutics Resources Sdn Bhd
• Contact: Jezamine Lim, PhD
• Phone: +60176073103
• Email: info[@]cellbiopeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Buerger's Disease
• Chronic Limb-Threatening Ischemia
• Critical Limb Ischemia
• Ischemia
• Thromboangiitis Obliterans

Intervention

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).

Locations

Country	Name	City	State
Malaysia	Hospital Canselor Tunku Mukhriz	Kuala Lumpur

Sponsors (3)

Lead Sponsor	Collaborator
Cell Biopeutics Resources Sdn Bhd	National University of Malaysia, Stempeutics Research Pvt Ltd

Country where clinical trial is conducted

Malaysia, 

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* Note: There are 46 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in ischemic rest pain	Change in visual analog score (VAS) compared to screening	Screening (Day -14 to -1), Day 30, 90, 180 and 360
Primary	Change in size of the ulcer	Change in size of the ulcer compared to screening	Screening (Day -14 to -1), Day 30, 90, 180 and 360
Primary	Change in ankle brachial pressure index (ABPI)	Change in ankle brachial pressure index (ABPI) compared to screening	Screening (Day -14 to -1), Day 30, 90, 180 and 360
Primary	Change in total walking distance	Change in total walking distance on a treadmill compared to screening	Screening (Day -14 to -1), Day 30, 90, 180 and 360
Primary	Change in major amputation-free survival	Change in amputation-free survival compared to screening	Screening (Day -14 to -1), Day 30, 90, 180 and 360
Primary	Change in angiogenesis	Change in angiogenesis measured by digital subtraction angiogram (DSA) compared to screening	Screening (Day -14 to -1), Day 180
Secondary	The type of AE(s), number of AE(s) and proportion of patients with AE(s)	AE(s) will be monitored and recorded as voluntarily disclosed by the patients and as observed by the investigator throughout the study	Screening (Day -14 to -1)
Secondary	Incidence of abnormal laboratory test results (serum chemistry, haematology, liver function test)	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).	Screening (Day -14 to -1), Day 7, 30, 90, 180 and 360
Secondary	Incidence of abnormal urine test results	Urine test will be conducted. In case of abnormal results, they shall be recorded as an adverse event or excluded from study (screening).	Screening (Day -14 to -1), Day 180
Secondary	Incidence of abnormal TNF-a	TNF-a test will be conducted. In case of abnormal results, they shall be recorded as an adverse event or excluded from study (screening).	Screening (Day -14 to -1), Day 7 and 30
Secondary	Incidence of abnormal vital signs	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 study (screening).	Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360
Secondary	Incidence of abnormal physical examination	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 study (screening).	Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360
Secondary	Incidence of abnormal ECG parameters	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).	Screening (Day -14 to -1), Baseline, Day 7, 30, 90, 180 and 360
Secondary	Incidence of abnormal chest condition	Chest x-ray will be conducted. In case of abnormal conditions, they shall be recorded as an adverse event or excluded from study (screening).	Screening (Day -14 to -1), Day 180