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Safety and Efficacy of Allogeneic Cells for the Treatment of Intermittent Claudication(IC)

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: NCT01679990
Recruitment Status : Completed
First Posted : September 6, 2012
Last Update Posted : February 12, 2019
Information provided by (Responsible Party):
Pluristem Ltd.

Tracking Information
First Submitted Date  ICMJE September 2, 2012
First Posted Date  ICMJE September 6, 2012
Last Update Posted Date February 12, 2019
Study Start Date  ICMJE November 5, 2012
Actual Primary Completion Date March 29, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2012)
Log ratio of week 52 maximal walking distance(MWD)to baseline MWD [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Allogeneic Cells for the Treatment of Intermittent Claudication(IC)
Official Title  ICMJE A Phase II, Randomized, Double-Blind, Multicenter, Multinational, Placebo-Controlled, Parallel- Groups Study to Evaluate the Safety and Efficacy of Intramuscular Injections of Allogeneic PLX-PAD Cells for the Treatment of Subjects With Intermittent Claudication (IC)
Brief Summary

The objective of the study is to establish the safety profile of

Intramuscular PLX-PAD injections and to evaluate the clinical efficacy of it in IC subjects comprising of 4 treatment groups:

  1. Double treatment of PLX-PAD low dose
  2. Double treatment of PLX-PAD high dose
  3. Double treatment of Placebo
  4. Single treatment of PLX-PAD high dose and additional treatment of Placebo. Subjects will receive the assigned treatment twice to the affected leg, within 12-weeks interval between each treatment.

The study will be comprised of 5 stages:

Screening period of up to 4 weeks,first treatment of PLX-PAD or placebo followed by additional injection after 12 weeks and with follow-up of 12 months post second injection

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE
  • Intermittent Claudication
  • Peripheral Artery Disease
Intervention  ICMJE
  • Biological: PLX-PAD Low dose
  • Biological: PLX-PAD high doses
  • Biological: Double Placebo
  • Biological: high dose +Placebo
Study Arms  ICMJE
  • Experimental: PLX-PAD Low dose
    PLX-PAD double low doses
    Intervention: Biological: PLX-PAD Low dose
  • Active Comparator: PLX-PAD high doses
    PLX-PAD double high dose
    Intervention: Biological: PLX-PAD high doses
  • Placebo Comparator: Placebo
    Double Placebo doses
    Intervention: Biological: Double Placebo
  • Experimental: PLX-PAD high dose +Placebo
    High dose+Placebo
    Intervention: Biological: high dose +Placebo
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 Completed
Actual Enrollment  ICMJE
 (submitted: February 11, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2012)
Actual Study Completion Date  ICMJE February 9, 2019
Actual Primary Completion Date March 29, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult male or female subjects between 45 to 85 years of age (inclusive) at the time of screening visit.
  • Subjects with a diagnosis of peripheral artery disease, secondary to atherosclerosis, confirmed by one of the following criteria assessed at the screening visit:

    • Resting ankle-brachial index (ABI) ≤ 0.80 or
    • Resting ABI ≤ 0.90 and >20% decrease in ABI from rest to exercise when measured within 1 minute after treadmill exercise or
    • Toe-brachial index (TBI) ≤ 0.60
  • Lifestyle-limiting, moderate to severe claudication (symptoms present and stable for > 6 months and not significantly changed within the past 3 months prior to screening).
  • Evidence of significant (>50%) stenosis infra-inguinal occlusive disease as confirmed by documented results from Duplex, MRA, CTA and/or contrast angiogram completed within 3 months prior to screening.
  • The longest maximal walking distance (MWD) from the Screening Period exercise treadmill tests (ETT), utilizing a modified Gardner Protocol (Appendix I), must be between 1 and 10 minutes (inclusive).
  • Subjects who have persistent claudication symptoms despite having been recommended an exercise program if feasible, and or despite having been on a stable dose of Cilostazol, if indicated. Subjects should be Cilostazol free for at least 2 weeks prior to the first ETT.
  • Subjects should be receiving standard of care drugs for vascular disease including anti-platelet agent(s) and statin medication, as well as anti-hypertensive medication(s) and oral hypoglycemic agents/insulin, if indicated.
  • Signed written informed consent.

Exclusion Criteria:

  • Ischemic rest pain; ulceration or gangrene (Fontaine class III-IV; Rutherford category 4-6).
  • Failed lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within the prior one month of screening.
  • Planned revascularization (surgical or endovascular intervention) within 12 months after screening.
  • Lower extremity arteries inflow obstruction (defined as a greater than 50% stenosis of aorta, iliac and/or common femoral arteries).
  • History of Buerger's disease.
  • Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic blood pressure > 180 mmHg during screening).
  • Uncontrolled diabetes defined as glucose control HbA1c > 9% at screening.
  • Life-threatening ventricular arrhythmia - except in subjects with an implantable cardiac-defibrillator.
  • Serum Creatinine level>2.5mg/dl.
  • SGPT (ALT), SGOT (AST) >2.5 x upper limit of normal range.
  • Hemoglobin < 10 g/dl.
  • Unstable cardiovascular disease defined as myocardial infarction (STEMI or NSTEMI) within 3 months prior to screening, or unstable angina - characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged episodes.
  • Transient Ischemic Attack (TIA)/Stroke within 3 months prior to screening.
  • Subjects with severe congestive heart failure symptoms (i.e. NYHA Stage III to IV).
  • Subjects with Implant of mechanical prosthetic heart valve(s).
  • Pulmonary disease requiring supplemental oxygen treatment on a daily basis.
  • Severe, active infection of the involved extremity(ies), including osteomyelitis, fasciitis, or severe/purulent cellulitis.
  • History of malignancy within 5 years prior screening requiring chemotherapy and/or radiotherapy and/or immunotherapy, excluding basal or squamous cell carcinoma of the skin.
  • Exercise is limited by any condition other than IC, including but not limited to congestive heart failure, chronic pulmonary disease, angina pectoris, or degenerative joint disease.
  • Uninterrupted use of warfarin or non-steroidal anti-inflammatory agents (with the exception of ibuprofen at doses up to 1,200 mg/day or Diclofenac at dose of 75mg/day).
  • Subjects who are on oral anticoagulant therapy (warfarin, dabigatran, apixaban, endoxaban and rivaroxaban). Unless, upon primary care physician and/or Investigator's discretion the subjects who are on warfarin treatment can switch to Low Molecular Weight Heparin treatment (such as: Clexane) 5-7 days prior study treatment administration and return to warfarin treatment 24 hours post study treatment administration.
  • Subjects who are taking immunosuppressive treatment (including high dose steroids).
  • Known allergies to protein products (Bovine serum, or recombinant trypsin) used in the cell production process.
  • Known sensitivity to Gentamycin.
  • Known sensitivity to antihistamine drugs.
  • History of hospitalization due to allergic/hypersensitivity reaction to any substance (e.g. Food or drug).
  • Medical history of Human Immunodeficiency Virus (HIV) or syphilis positivity at time of screening.
  • Known active Hepatitis B, or Hepatitis C infection at the time of screening.
  • Pregnant or breast-feeding women or women of childbearing age not protected by an effective contraceptive method of birth control (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide).
  • In the opinion of the Investigator, the subject is unsuitable for participating in the study.
  • Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s).
  • Subjects that have prior exposure to gene or cell based therapy.
  • Subjects who are legally detained in an official institute.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 85 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 Germany,   Israel,   Korea, Republic of,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01679990
Other Study ID Numbers  ICMJE PLX 1204-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Pluristem Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Pluristem Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Douglas Denham, DO Clinical Trials of Texas, Inc. 7940 Floyd Curl drive, Suite 700, San Antonio, Texas 78229
Principal Investigator: James Hampsey, MD Tampa Bay Medical research, 3251 McMullen Booth Road, STE 303, Clearwater, FL 33761
Principal Investigator: Schulyer Jones, MD Duke University,Durham, North Carolina, 27705, USA
Principal Investigator: Bret Weichmann, MD Florida research Network, LLC 6800NW 9th Blvd Suite1, Gainesville, Florida 32605
Principal Investigator: Jeffrey W Olin, DO Cardiovascular Institute, Mount Sinai School of Medicine , One Gustave L. Levy Place, New York, NY 10029
Principal Investigator: Alan T Hirsch, MD Cardiovascular Division, MMC 508, University of Minnesota Medical school, Minneapolis, MN 55455
Principal Investigator: Sibu P. Saha, MD University of Kentucky, Lexington, KY 40506-0057
Principal Investigator: David L Fried, MD Omega Medical Research, Warwick, RI 02886
Principal Investigator: Berthold Amann, MD Franziskus-Krankenhaus, Berlin Germany
Principal Investigator: Norbert Weiss, MD Universitätsklinikum Carl Gustav Carus, Dresden, Germany
Principal Investigator: Sigrid Nikol, MD ASKLEPIOS Klinik St. Georg, Hamburg Germany
Principal Investigator: Malcolm Foster, MD Turkey Creek Medical Center, Knoxville TN 37934
Principal Investigator: Kathleen Cullen, MD DMI Research, 6699 90th Ave. North, Pinellas Park FL
Principal Investigator: Mohler Emile, M.D Hospital of the University of Pennsylvania, Philadelphia, PA 19104
Principal Investigator: Nadarajah Janaki, M.D Aiyan Diabetes Center, Evans, GA 30809
Principal Investigator: Reuven Zimlichman, MD Edith Wolfson Medical Center,62 HaLohamim Street, Holon, Israel
Principal Investigator: Changyoung Lim, MD CHA Bundang Medical Center, CHA University, 59 Yatap-ro Bundang-Gu, Seongnam-Si, Gyeonggi-do 463-712, Korea
Principal Investigator: Weonyong Lee, MD Hallym University Sacred Heart Hospital 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Korea
Principal Investigator: Sungwon Chung, MD Pusan National University Hospital 179 Gudeok-Ro Seo-Gu, Busan, 602-739, Korea
Principal Investigator: Yousun Hong, MD Ajou University School of Medicine
Principal Investigator: Jaeseung Shin, MD Korea University
Principal Investigator: Kwangjo Cho, MD Dong-A University Hospital
Principal Investigator: Dokyun Kim, MD National Health Insurance Service Ilsan Hospital
Principal Investigator: Joonhyuk Kong, MD Kangbuk Samsung Hospital
Principal Investigator: Stefan Betge, MD Universitätsklinikum Jena
Principal Investigator: Holger Reinecke, MD Universitätsklinikum Münster
Principal Investigator: Oliver Müller, MD Universitätsklinik Heidelberg
Principal Investigator: Erwin Blessing, MD Klinikum Karlsbad-Langensteinbach
Principal Investigator: Thomas Zeller, MD Universtiäts-Herzzentrum Freiburg und Bad-Krozingen
Principal Investigator: Christine Espinola-Klein, MD Johannes Gutenberg University Mainz
PRS Account Pluristem Ltd.
Verification Date January 2017

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