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A Safety and Efficacy Study of Autologous Bone Marrow Derived Mesenchymal Stem Cells in Critical Limb Ischemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02477540
Recruitment Status : Withdrawn (Study was stopped by sponsers internal reason.)
First Posted : June 22, 2015
Last Update Posted : March 22, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmicell Co., Ltd.

Tracking Information
First Submitted Date  ICMJE June 10, 2015
First Posted Date  ICMJE June 22, 2015
Last Update Posted Date March 22, 2019
Estimated Study Start Date  ICMJE December 2019
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
Ankle Brachial Pressure Index, ABPI [ Time Frame: 6 months after BM-MSC therapy ]
Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference of between the two visits(Screening and 6 month post treatment) before and after treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2015)
Ankle Brachial Pressure Index, ABPI [ Time Frame: 6 months after BM-MSC therapy ]
Change History Complete list of historical versions of study NCT02477540 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Collateral vessel formation on digital subtraction angiography (DSA) [ Time Frame: 6 months after BM-MSC therapy ]
    Analyze the difference of pre and post treatment using McNemar test for homogeneity test.
  • Difference of Wound size [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference of pre and post treatment Healing of ulcerations (change in size of ulcers) or reduction of ulcer area in the target limb.
  • Improved transcutaneous oxygen pressure (TCPO2) [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference of pre and post treatment transcutaneous oxygen pressure (TCPO2).
  • Pain on the Visual Analogue Scale(VAS) [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference of pre and post Visual Analogue Scale(VAS). Visual Analogue Scale(VAS): Using a ruler, the score is determined by mea-suring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. the following cut points on the pain VAS have been recommended: no pain (0-4 mm), mild pain(5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm)
  • Reduced limb amputation [ Time Frame: 6 months after BM-MSC therapy ]
    Described and define as minor amputation is below midtarsal level, major amputation is more than midtarsal level.
  • Temperature change on thermography [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference of pre and post thermography.
  • Dose about using analgesic medicine [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference between pre and post dose of the using analgesic medicine.
  • Change in Rutherford classification [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference of pre and post Rutherford classification. Rutherford classification: commonly used clinical staging system for describing peripheral arterial disease. Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters. Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene
  • Frequency about using analgesic medicine [ Time Frame: 6 months after BM-MSC therapy ]
    Use Student's paired t-test or Wilcoxon's signed rank test to compare the difference between pre and post frequency of the using analgesic medicine.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2015)
  • Collateral vessel formation on digital subtraction angiography (DSA) [ Time Frame: 6 months after BM-MSC therapy ]
  • Healing of ulcerations or reduction of ulcer area in the target limb [ Time Frame: 6 months after BM-MSC therapy ]
  • Improved transcutaneous oxygen pressure (TCPO2) [ Time Frame: 6 months after BM-MSC therapy ]
  • Improved visual analog scale (VAS) [ Time Frame: 6 months after BM-MSC therapy ]
  • Reduced limb amputation [ Time Frame: 6 months after BM-MSC therapy ]
  • Temperature change on thermography [ Time Frame: 6 months after BM-MSC therapy ]
  • Dose and frequency in use of a analgesic medicine [ Time Frame: 6 months after BM-MSC therapy ]
  • Change in Rutherford classification [ Time Frame: 6 months after BM-MSC therapy ]
Current Other Pre-specified Outcome Measures
 (submitted: March 21, 2019)
  • For safety analysis we will observed clinical laboratory tests, physical examinations, tumor marker tests [ Time Frame: 12 months after BM-MSC therapy ]
    Analyze using McNemar's test by making a table of changes that occurred in the test. clinical laboratory tests(Follow the unit of each institution): <Blood>
    • WBC, RBC, Hb, Hct, Platelets count, WBC Differential count, BUN, ALT, AST, Glucose, Total bilirubin, Total Cholesterol <Urine>
    • Protein, Glucose, Blood, Ketone, Billrubin, Urobillnogen
    physical examinations: -Allergy, Cardiovascular, Respiratory, Gastrointestinal /Liver biliary, Metabolic / endocrine, Kidney / urinary system, Reproductive, Musculoskeletal, Skin and connective, Nervous, Psyatric, Others tumor marker tests(Follow the unit of each institution):
    • AFP
    • CEA
    • CA15-3(female)
    • PSA(male)
  • occurrence and severity of adverse events [ Time Frame: 12 months after BM-MSC therapy ]
    Analyze the adverse events by using seriousness, severity and relevance of IP.
Original Other Pre-specified Outcome Measures
 (submitted: June 19, 2015)
Safety Evaluation: The safety evaluation in this clinical trial is performed with variables, such as occurrence and severity of adverse events, clinical laboratory tests, physical examinations and tumor marker tests. [ Time Frame: 12 months after BM-MSC therapy ]
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of Autologous Bone Marrow Derived Mesenchymal Stem Cells in Critical Limb Ischemia
Official Title  ICMJE An Open Labeled, Single-center, Phase I Study Assessing the Safety and Efficacy of Autologous Bone Marrow Derived Mesenchymal Stem Cells in Critical Limb Ischemia
Brief Summary This clinical trial to study the Safety and Efficacy of Autologous Mesenchymal stem cells in critical limb ischemia.
Detailed Description

If the participant voluntarily agrees to participate in the clinical trial before registration, the investigator conducts a screening test to evaluate the participant's suitability.

A participant that satisfies all inclusion and exclusion criteria is assigned a test group(2-time injection group).

Participants conduct cell therapy within 30 days after bone marrow aspiration, and will re-inject autologous mesenchymal stem cells within 30 days after first injection.

Participants will make a total of 5 hospital visits after registration, and Safety and Efficacy will be evaluated based on a fixed procedure on every visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Critical Limb Ischemia
Intervention  ICMJE Drug: Cellgram-CLI

Appearance: White cell suspension is filled in a clear plastic syringe, and fixed with an occlude on the prefilled syringe tip

Main ingredient: Autologous bone marrow-derived mesenchymal stem cells

Dosage: 50,000,000 cells/10ml, 2-time injection

Storage: An airtight container, 20~25℃

Injection Method: Intramuscular

Other Name: Autologous bone marrow derived Mesenchymal Stem Cells
Study Arms  ICMJE Experimental: 2-time injection group : Cellgram-CLI
Within 30 days after extracting bone marrow, autologous bone marrow-derived mesenchymal stem cells is directly injected into the lesion. Then the second cell is injected within 30 days after the first cell injection.
Intervention: Drug: Cellgram-CLI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 19, 2015)
10
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age from 20 to 80 years
  • Patients with resting pain or ulceration of limb (Rutherford's class: II-4, III-5 or III-6)
  • Ankle Brachial Pressure Index (ABPI) ≤ 0.6 or TCPO2 ≤ 60mmHg in the foot
  • Patients who were unsuitability for percutaneous transluminal angioplasty or a bypass operation
  • Patients who are not expected other treatments for at least 6 months
  • Patients who can agree to participate in the clinical trial by oneself or by one's legal representative
  • Patients who can conduct the clinical trial according to the protocol

Exclusion Criteria:

  • Buerger's disease
  • History of hematologic disease
  • Patients who are at risk of embolism due to atrial fibrillation
  • Primary hematologic disease, including hypercoagulable states
  • Entrapment syndrome
  • Patients with osteomyelitis
  • Patients whose blood serum AST(Aspartate transaminase)/ALT(Alanine Transaminase) rates are more than three times the normal maximum rate, or whose creatinine rates are more than 1.5 times the normal maximum rate
  • Patients with history of anaphylaxis to gentamicin
  • Patients with hypersensitivity of bovine-derived ingredients
  • Patients with chronic heart failure, Glomerular disease and Obstructive pulmonary disease
  • Patients with Stroke or transient ischemic attack within 6 months prior to registration
  • Patients tested positive for HIV(Human Immunodeficiency Virus), HCV(Hepatitis C Virus), HBV(Hepatitis B Virus) and Syphilis
  • Patients with history of aorta and artery bypass operation, or angioplasty within 2 months recently
  • Patients in need of a immediate amputation and have a potentially life-threatening complications of critical ischemia
  • Patients with history of cell therapy
  • Type I diabetes
  • Uncontrolled diabetes mellitus (HgbA1C>8%)
  • Uncontrolled hypertension
  • Has a medical record of solid cancer, or diagnosed with solid cancer and currently receiving cancer treatment
  • Positive of tumor markers test(AFP((Alpha fetoprotein), CEA(Carcinoembryonic antigen), CA15-3(Cancer antigen 15-3 for breast cancer) and PSA(Prostate-specific antigen), or have received a diagnosis of cancer based on National cancer screening program
  • Pregnancy, possible candidate for pregnancy or lactating women
  • Infectious disease
  • Administrating of immunosuppressive agents, corticosteroid formulation and cell toxicity formulation, or requiring administration of the test period
  • Patients already enrolled in another clinical trials or completed within 3 months
  • Patients who cannot adapt to the protocol and follow-up observation
  • Patients who has experienced drug abuse for the past 1 year
  • Patients with any disease or condition which the investigator fell would interfere with trial or the safety of the subject
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02477540
Other Study ID Numbers  ICMJE Cellgram-CLI
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmicell Co., Ltd.
Study Sponsor  ICMJE Pharmicell Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: WoongChol Kang, MD, Ph.D Gachon University Gil Medical Center
PRS Account Pharmicell Co., Ltd.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP