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

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

Tracking Information

• First Submitted Date: September 2, 2012
• First Posted Date: September 6, 2012
• Last Update Posted Date: February 12, 2019
• Study Start Date: November 5, 2012
• Actual Primary Completion Date: March 29, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 5, 2012): Log ratio of week 52 maximal walking distance(MWD)to baseline MWD [ Time Frame: 12 months ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Allogeneic Cells for the Treatment of Intermittent Claudication(IC)
• 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)

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment

Condition

• Intermittent Claudication
• Peripheral Artery Disease

Intervention

• Biological: PLX-PAD Low dose
• Biological: PLX-PAD high doses
• Biological: Double Placebo
• Biological: high dose +Placebo

Study Arms

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 11, 2019): 180
• Original Estimated Enrollment (submitted: September 5, 2012): 150
• Actual Study Completion Date: February 9, 2019
• Actual Primary Completion Date: March 29, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 45 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Israel, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT01679990
• Other Study ID Numbers: PLX 1204-01
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pluristem Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pluristem Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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: 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