Efficacy and Safety of Mesenchymal Stem Cell Clusters in Patients with Critical Limb Ischemia

NCT04661644 | Completed Phase 1

• 1 other identifier: SB-AC-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is designed as a Phase 1/2a clinical trial targeting patients with critical limb ischemia. The trial is composed of Phase 1 to assess the tolerability and safety and Phase 2a to assess the safety and efficacy of the investigational product(A cluster of adipose-derived mesenchymal stem cells (3D-A) (cluster of adipose- derived mesenchymal stem cells)) and proceeds in that order.

Conditions

Critical Limb Ischemia

Keywords

Adipose-derived mesenchymal stem cells; Critical limb ischemia; Stem cells; Ischemia; S.Biomedics

Outcome Measures

Primary Outcomes (10)

• Changes in ischemic pain

  Changes in 10 cm VAS (Visual analog score) measurement shall be recorded, and statistically analyzed (mean, median, max, min, STD, average). The degree of change shall be compared between the test groups using two sample t-test or Wilcoxon's rank sum test)

  The degrees of changes in VAS measurement on week 4, week 12, week 24, compared to the baseline.

• Changes in pain-free walking distance

  Changes in maximum walking distance on a treadmill shall be measured, and statistically analyzed(mean, median, max, min, STD, average). The degree of change shall be compared between the test groups using two sample t-test or Wilcoxon's rank sum test)

  The degrees of changes in pain-free walking distance on week 4, week 12, week 24, compared to the baseline.

• Changes in TBI (Toe Brachial Index)

  Changes in TBI (Toe Brachial Index) shall be recorded, and statistically analyzed (mean, median, max, min, STD, average). The degree of change shall be compared between the test groups using two sample t-test or Wilcoxon's rank sum test)

  The degrees of changes in TBI on week 4, week 12, week 24, compared to the baseline.

• Changes in ABI (Ankle Brachial Index)

  Changes in ABI (Ankle Brachial Index) shall be recorded, and statistically analyzed (mean, median, max, min, STD, average). The degree of change shall be compared between the test groups using two sample t-test or Wilcoxon's rank sum test)

  The degrees of changes in ABI on week 4, week 12, week 24, compared to the baseline.

• Change in size of the Ulcer

  The size of the largest ulcer shall be measured and statistically analyzed (mean, median, max, min, STD, average). The degree of change shall be compared between the test groups using two sample t-test or Wilcoxon's rank sum test)

  The degrees of changes in Ulcer size on week 4, week 12, week 24, compared to the baseline.

• Determination of maximum tolerable dose according to DLT occurrence

  Occurrence of adverse drug reactions that are definitely related to the administrated drug are monitored. Maximum tolerable dose is determined when ADR with grade 3 or higher with accordance to CTCAE version 5.0 has occurred to at least one of the three subjects.

  Occurrence of ADR is monitored throughout the baseline to week 4 during phase 1.

• Incidence of abnormal laboratory tests results

  The following laboratory tests are conducted. In case the results are abnormal, it shall be recorded as a adverse event or excluded from study (screening). Hematologic Test: WBC, RBC, Hemoglobin, Hematocrit, Platelets count, Blast, Promyelocyte, Metamyelocyte, Neutrophil (Seg, Band), Eosinophil, Basophil, Lymphocyte, Monocyte, Atypical Lymphocyte, Immature cell, Plasma cell, Nucleated RBC, Abnormal lymphoid cell Blood Chemistry Test: Total protein, Albumin, Globulin, Total Bilirubin, AST, ALT, ALP, BUN, Creatinine, Glucose, Uric Acid, Estimated GFR, Ca, P, CRP, CPK Urine Test: Specific gravity, pH, Glucose, Albumin, Bilirubin, Urobilinogen, Ketone, Blood, Nitrite, Leukocyte Esterase

  Laboratory tests are performed on screening(-4~-2 week), baseline, 1 day after the baseline, and on week 4, week 12, week 24, compared to the baseline.

• Incidence of abnormal blood pressure

  Systolic/Diastolic blood pressure is measured after relaxing in sitted position for 5 minutes. In case the results are clinically abnormal, it shall be recorded as an adverse event or excluded from study (screening).

  Blood pressure is measured throughout the study (on screening visit(4~2 week before the baseline), base line, a day after the baseline, week 4, 12, 24 compared to the baseline.)

• Incidence of abnormal temperature

  Temperature is measured via eardrum after relaxing in sitted position for 5 minutes. In case the results are clinically abnormal, it shall be recorded as an adverse event.

  Temperature is measured throughout the study (on screening visit(4~2 week before the baseline), base line, a day after the baseline, week 4, 12, 24 compared to the baseline.)

• Incidence of abnormal physical condition

  Appearance, skin, head, neck, heart, stomach, urology system, reproductive system, limbs, musculoskeletal system, nervous system, lymphatic glands and etc are examined. In case any clinically abnormal condition has been monitored, it shall be recorded as an adverse event.

  Examined on every visits, throughout the study (on screening visit(4~2 week before the baseline), base line, a day after the baseline, week 4, 12, 24 compared to the baseline.)

Study Arms (2)

Test Group 1 (Low Dose)

EXPERIMENTAL

\- Administration Method: 1 mL is withdrawn from 1 vial of clusters of adipose-derived mesenchymal stem cells, composed of adipose-derived mesenchymal stem cells and diluted with 20 mL of saline, which is divided into 1 cc pre-filled syringes and administered in 20 divided doses to 15-20 parts of the muscle in divided doses along the working areacourse of the tibial artery and peroneal artery below the knee joint (above the lower ischemic area) of the subject (above the lower ischemic area) of the subjects under general anesthesia or spinal anesthesia so that the entire diluted solution is administered.

Biological: Clusters of adipose-derived mesenchymal stem cells (Dose: 1 x 10^7 cells/1 mL/vial)

Test Group 2 (High Dose)

EXPERIMENTAL

\- Administration Method: 1 mL is withdrawn from 1 vial of clusters of adipose-derived mesenchymal stem cells, composed of adipose-derived mesenchymal stem cells and diluted with 20 mL of saline, then administered to 15-20 parts of the muscle along the working areacourse of the tibial artery and peroneal artery below the knee joint (above the lower ischemic area) of the subject (above the lower ischemic area) of the subjects under general anesthesia or spinal anesthesia.

Biological: Clusters of adipose-derived mesenchymal stem cells (Dose: 1 x 10^8 cells/1 mL/vial)

Interventions

Clusters of adipose-derived mesenchymal stem cells (Dose: 1 x 10^7 cells/1 mL/vial) BIOLOGICAL

Dose: 1 x 10\^7 cells/1 mL/vial (1,000 clusters of adipose-derived mesenchymal stem cells)

Test Group 1 (Low Dose)

Clusters of adipose-derived mesenchymal stem cells (Dose: 1 x 10^8 cells/1 mL/vial) BIOLOGICAL

Dose: 1 x 10\^8 cells/1 mL/vial (10,000 clusters of adipose-derived mesenchymal stem cells)

Test Group 2 (High Dose)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 19 or older
• A person diagnosed with critical limb ischemia due to peripheral artery stenosis or obstructive occlusive disease (Rutherford category 4, 5, 6)
• Patients with critical limb ischemia where symptoms do not improve even after medication treatment for more than 3 months\[1\]
• Persons who voluntarily agreed to participate in this clinical trial

You may not qualify if:

• Persons whose life expectancy is less than 6 months
• Patients who underwent surgery and interventional procedures (percutaneous vascular intervention, vascular reconstruction, etc.) in the same disease within 3 months of screening
• Patients in need of interventional procedure or surgery
• Patients with a history of administration of other cell therapy products
• Persons who have received systemic immunosuppression treatment within 3 months of screening
• Persons with a history of a malignant tumor within 5 years of screening (However, non-metastatic basal cell skin carcinoma, squamous cell carcinoma of the skin or carcinoma in situ of the cervix that does not recur for at least 1 year before the registration are excluded)
• Persons with a hematologic disease with major bleeding or bleeding predisposition within 3 months of screening
• Women who are pregnant, breastfeeding or planning to become pregnant during the clinical trial period or women of childbearing potential who do not use medically acceptable birth control
• \*Medically acceptable contraception:
• Medicine: Oral contraceptives, skin patches or progestin medications (Transplant or injection)
• Diaphragm: Condoms, diaphragms, intrauterine devices (IUDs), vaginal suppositories
• Abstinence: Absolute abstinence (However, periodic abstinence (e.g., calendar method, ovulation method, sympto-thermal method) and control are not considered acceptable contraceptive methods.)
• Persons who participated in other clinical trials within 3 months of screening
• Persons who were administered prohibited concomitant medications related to this clinical trial
• Persons with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than twice the normal upper limit at the time of screening

Sponsors & Collaborators

• S.Biomedics Co., Ltd.: lead
• Dt&Sanomedics: collaborator

Study Sites (1)

Samsung Medical Center

Seoul, Seoul, 06351, South Korea

Location

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MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dong-Ik Kim, PhD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 is conducted to evaluate the tolerability of the IP Subjects receive the IP once and are checked for adverse events. Subjects are evaluated for adverse events after the administration of the IP by registering 3 subjects each at the dosing phase. If the maximum tolerated dose (MTD) is determined with the test group 2 (high dose) in the Phase 1, the Phase 2a clinical trial will be conducted. However, if 1 adverse events occur, the test group 2 will be considered as the maximum tolerated dose (MTD), or but only the test group 1 will proceed to Phase 2a. If 2 adverse events occur, a dose smaller than test group 1 (low dose) is determined to be the maximum tolerated dose. The Phase 2a clinical trial will not proceed and the clinical trial will end. If tolerability and safety are secured, subjects meeting the final inclusion criteria are assigned to Phase 2a, admitted by the same procedure, and administered the IP once. Safety and efficacy assessments are performed.

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: December 10, 2020
• Study Start: November 4, 2020
• Primary Completion: April 22, 2024
• Study Completion: July 1, 2024
• Last Updated: August 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)