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

NCT ID: NCT01679990

Last Updated: 2019-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-05
• Study Completion Date: 2019-02-09

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

Conditions

Intermittent Claudication; Peripheral Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PLX-PAD Low dose

PLX-PAD double low doses

Group Type: EXPERIMENTAL

PLX-PAD Low dose

Intervention Type: BIOLOGICAL

PLX-PAD high doses

PLX-PAD double high dose

Group Type: ACTIVE_COMPARATOR

PLX-PAD high doses

Intervention Type: BIOLOGICAL

Placebo

Double Placebo doses

Group Type: PLACEBO_COMPARATOR

Double Placebo

Intervention Type: BIOLOGICAL

PLX-PAD high dose +Placebo

High dose+Placebo

Group Type: EXPERIMENTAL

high dose +Placebo

Intervention Type: BIOLOGICAL

Interventions

PLX-PAD Low dose

Intervention Type: BIOLOGICAL

PLX-PAD high doses

Intervention Type: BIOLOGICAL

Double Placebo

Intervention Type: BIOLOGICAL

high dose +Placebo

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pluristem Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Douglas Denham, DO

Role: PRINCIPAL_INVESTIGATOR

Clinical Trials of Texas, Inc. 7940 Floyd Curl drive, Suite 700, San Antonio, Texas 78229

James Hampsey, MD

Role: PRINCIPAL_INVESTIGATOR

Tampa Bay Medical research, 3251 McMullen Booth Road, STE 303, Clearwater, FL 33761

Schulyer Jones, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University,Durham, North Carolina, 27705, USA

Bret Weichmann, MD

Role: PRINCIPAL_INVESTIGATOR

Florida research Network, LLC 6800NW 9th Blvd Suite1, Gainesville, Florida 32605

Jeffrey W Olin, DO

Role: PRINCIPAL_INVESTIGATOR

Cardiovascular Institute, Mount Sinai School of Medicine , One Gustave L. Levy Place, New York, NY 10029

Alan T Hirsch, MD

Role: PRINCIPAL_INVESTIGATOR

Cardiovascular Division, MMC 508, University of Minnesota Medical school, Minneapolis, MN 55455

Sibu P. Saha, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky, Lexington, KY 40506-0057

David L Fried, MD

Role: PRINCIPAL_INVESTIGATOR

Omega Medical Research, Warwick, RI 02886

Berthold Amann, MD

Role: PRINCIPAL_INVESTIGATOR

Franziskus-Krankenhaus, Berlin Germany

Norbert Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Carl Gustav Carus, Dresden, Germany

Sigrid Nikol, MD

Role: PRINCIPAL_INVESTIGATOR

ASKLEPIOS Klinik St. Georg, Hamburg Germany

Malcolm Foster, MD

Role: PRINCIPAL_INVESTIGATOR

Turkey Creek Medical Center, Knoxville TN 37934

Kathleen Cullen, MD

Role: PRINCIPAL_INVESTIGATOR

DMI Research, 6699 90th Ave. North, Pinellas Park FL

Mohler Emile, M.D

Role: PRINCIPAL_INVESTIGATOR

Hospital of the University of Pennsylvania, Philadelphia, PA 19104

Nadarajah Janaki, M.D

Role: PRINCIPAL_INVESTIGATOR

Aiyan Diabetes Center, Evans, GA 30809

Reuven Zimlichman, MD

Role: PRINCIPAL_INVESTIGATOR

Edith Wolfson Medical Center,62 HaLohamim Street, Holon, Israel

Changyoung Lim, MD

Role: PRINCIPAL_INVESTIGATOR

CHA Bundang Medical Center, CHA University, 59 Yatap-ro Bundang-Gu, Seongnam-Si, Gyeonggi-do 463-712, Korea

Weonyong Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Hallym University Sacred Heart Hospital 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Korea

Sungwon Chung, MD

Role: PRINCIPAL_INVESTIGATOR

Pusan National University Hospital 179 Gudeok-Ro Seo-Gu, Busan, 602-739, Korea

Yousun Hong, MD

Role: PRINCIPAL_INVESTIGATOR

Ajou University School of Medicine

Jaeseung Shin, MD

Role: PRINCIPAL_INVESTIGATOR

Korea University

Kwangjo Cho, MD

Role: PRINCIPAL_INVESTIGATOR

Dong-A University Hospital

Dokyun Kim, MD

Role: PRINCIPAL_INVESTIGATOR

National Health Insurance Service Ilsan Hospital

Joonhyuk Kong, MD

Role: PRINCIPAL_INVESTIGATOR

Kangbuk Samsung Hospital

Stefan Betge, MD

Role: PRINCIPAL_INVESTIGATOR

Jena University Hospital

Holger Reinecke, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Münster

Oliver Müller, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinik Heidelberg

Erwin Blessing, MD

Role: PRINCIPAL_INVESTIGATOR

Klinikum Karlsbad-Langensteinbach

Thomas Zeller, MD

Role: PRINCIPAL_INVESTIGATOR

Universtiäts-Herzzentrum Freiburg und Bad-Krozingen

Christine Espinola-Klein, MD

Role: PRINCIPAL_INVESTIGATOR

Johannes Gutenberg University Mainz

Locations

Cardiology, P. C. and Center for Therapeutic Angiogenesis

Birmingham, Alabama, United States

Tampa Bay Medical Research

Clearwater, Florida, United States

Florida Researc Network, LLC

Gainesville, Florida, United States

DMI Research

Pinellas Park, Florida, United States

Dr. Nadarajah Janaki

Evans, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Kentucky Research Foundation

Lexington, Kentucky, United States

Cardiovascular Division, MMC, University of Minnesota

Minneapolis, Minnesota, United States

Cardiovascular Institute, Mount Sinai School of Medicine

New York, New York, United States

Duke University

Durham, North Carolina, United States

Dr. Mohler Emile

Philadelphia, Pennsylvania, United States

Omega Medical Center

Warwick, Rhode Island, United States

Turkey Creek Medical Center

Knoxville, Tennessee, United States

Clinical Trials of Texas

San Antonio, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Universtiäts-Herzzentrum Freiburg und Bad-Krozingen

Bad Krozingen, , Germany

Franziskus-Krankenhaus

Berlin, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

ASKLEPIOS Klinik St. Georg

Hamburg, , Germany

Universitätsklinik Heidelberg

Heidelberg, , Germany

Universitätsklinikum Jena

Jena, , Germany

SRH Klinikum Karlsbad-Langensteinbach

Karlsbad, , Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Universitätsklinikum Münster

Münster, , Germany

"Mor" Instituite, Horev M.C

Haifa, , Israel

Edith Wolson Medical Center

Holon, , Israel

Dong-A University Hospital

Seo-gu, Busan, South Korea

Korea University Ansan Hospital

Ansan, Gyeonggi-do, South Korea

National Health Insurance Service Ilsan Hospital

Ilsandong-gu, Goyang-si, Gyeonggi-do, South Korea

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Dr. Sungwon Chung

Busan, , South Korea

Dr. Weonyong Lee

Gyeonggi-do, , South Korea

Dr. Changyoung Lim

Gyeonggi-do, , South Korea

Kangbuk Samsung Medical Center

Seoul, , South Korea

Countries

United States; Germany; Israel; South Korea

Other Identifiers

PLX 1204-01

Identifier Type: -

Identifier Source: org_study_id