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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Pluristem Ltd.
Sponsor:
Information provided by (Responsible Party):
Pluristem Ltd.
ClinicalTrials.gov Identifier:
NCT01679990
First received: September 2, 2012
Last updated: July 3, 2014
Last verified: July 2014
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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   
Korea, Republic of
Dr. Sungwon Chung Recruiting
Busan, Korea, Republic of, 602-739
Contact: Sungwon Chung, MD    81-10-6848-7263    chungsungwoon@hanmail.net   
Dr. Weonyong Lee Recruiting
Gyeonggi-do, Korea, Republic of, 431-796
Contact: Weonyong Lee, MD    82-10-9050-5662    yshongjin@ajou.ac.kr   
Dr. Changyoung Lim Recruiting
Gyeonggi-do, Korea, Republic of, 463-712
Contact: Changyoung Lim, MD    82-10-6232-1079    cylimmd@cha.ac.kr   
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
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
  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: July 3, 2014
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
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Peripheral Vascular Diseases
Signs and Symptoms
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014