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

This study is currently recruiting participants.
Verified December 2013 by Pluristem Ltd.
Sponsor:
Information provided by (Responsible Party):
Pluristem Ltd.
ClinicalTrials.gov Identifier:
NCT01679990
First received: September 2, 2012
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Intermittent Claudication
Peripheral Artery Disease
Biological: PLX-PAD Low dose
Biological: PLX-PAD high doses
Biological: Double Placebo
Biological: high dose +Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Pluristem Ltd.:

Primary Outcome Measures:
  • Log ratio of week 52 maximal walking distance(MWD)to baseline MWD [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: October 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PLX-PAD Low dose
PLX-PAD double low doses
Biological: PLX-PAD Low dose
Active Comparator: PLX-PAD high doses
PLX-PAD double high dose
Biological: PLX-PAD high doses
Placebo Comparator: Placebo
Double Placebo doses
Biological: Double Placebo
Experimental: PLX-PAD high dose +Placebo
High dose+Placebo
Biological: high dose +Placebo

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult male or female subjects between 45 to 80 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01679990

Locations
United States, Florida
Tampa Bay Medical Research Recruiting
Clearwater, Florida, United States, 33761
Contact: James Hampsey, MD       hampsey@tbmr.net   
Principal Investigator: James Hampsey, MD         
Florida Researc Network, LLC Recruiting
Gainesville, Florida, United States, 32605
Contact: Kurt Malphurs, MD       kurtm@flrnetwork.com   
Principal Investigator: Bret Weichmann, MD         
DMI Research Recruiting
Pinellas Park, Florida, United States, 33782
Contact: Kathleen Cullen, MD    727-531-2848    kcullen@dmiresearch.com   
Principal Investigator: Kathleen Cullen, MD         
United States, Georgia
Dr. Nadarajah Janaki Recruiting
Evans, Georgia, United States
Contact: Nadarajah Janaki, MD    706-868-0319    jnadarajah@pol.net   
United States, Kentucky
University of Kentucky Research Foundation Recruiting
Lexington, Kentucky, United States, 40506-0057
Contact: Sibu P. Saha, MD    859-257-8250    ssaha2@email.uky.edu   
Principal Investigator: Sibu P Saha, MD         
United States, Minnesota
Cardiovascular Division, MMC, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Alan T Hirsch, MD       Hirsc005@umn.edu   
Principal Investigator: Alan T Hirsch, MD         
United States, New York
Cardiovascular Institute, Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Jeffrey W Olin, DO       Jeffrey.olin@mountsinai.org   
Principal Investigator: Jeffrey W Olin, DO         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States
Contact: Jones Schulyer, MD       schuyler.jones@dm.duke.edu   
Principal Investigator: Jones Schulyer, MD         
United States, Pennsylvania
Dr. Mohler Emile Recruiting
Philadelphia, Pennsylvania, United States
Contact: Mohler Emile, M.D    215-662-3275    Emile.Mohler@uphs.upenn.edu   
United States, Rhode Island
Omega Medical Center Recruiting
Warwick, Rhode Island, United States, 02886
Contact: David L Fried, MD    401-739-9350    dr.fried@omegamedicalresearch.com   
Principal Investigator: David L Fried, MD         
United States, Tennessee
Turkey Creek Medical Center Recruiting
Knoxville, Tennessee, United States, 10820
Contact: Malcolm Foster, MD    865-218-7535    malcolm.foster@etc.com   
Principal Investigator: Malcolm Foster, MD         
United States, Texas
Clinical Trials of Texas Recruiting
San Antonio, Texas, United States, 78229
Contact: Douglas Denham, DO       ddenham@cttexas.com   
Principal Investigator: Douglas Denham, DO         
Germany
Franziskus-Krankenhaus Recruiting
Berlin, Germany
Contact: André Schmidt-Lucke, MD    +493026383600    andre.schmidt-lucke@franziskus-berlin.de   
Principal Investigator: André Schmidt-Lucke, MD         
Universitätsklinikum Carl Gustav Carus Recruiting
Dresden, Germany
Contact: Norbert Weiss, MD    +493514583659    Norbert.Weiss@uniklinikum-dresden.de   
Principal Investigator: Norbert Weiss, MD         
ASKLEPIOS Klinik St. Georg Recruiting
Hamburg, Germany
Contact: Sigrid Nikol, MD    +49401818852401    s.nikol@asklepios.com   
Principal Investigator: Sigrid Nikol, MD         
Israel
Edith Wolson Medical Center Recruiting
Holon, Israel, 58100
Contact: Reuven Zimlichman, MD    972-54-7525855    zimlichman@wolfson.health.gov.il   
Sponsors and Collaborators
Pluristem Ltd.
Investigators
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: André Schmidt-Lucke, 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
  More Information

No publications provided

Responsible Party: Pluristem Ltd.
ClinicalTrials.gov Identifier: NCT01679990     History of Changes
Other Study ID Numbers: PLX 1204-01
Study First Received: September 2, 2012
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Intermittent Claudication
Peripheral Arterial Disease
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Signs and Symptoms
Atherosclerosis
Peripheral Vascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014