Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects With Critical Limb Ischemia (CLI) With Minor Tissue Loss Who Are Unsuitable for Revascularization

Lead Sponsor

Pluristem Ltd.

Source

Pluristem Ltd.

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

Brief Summary

This will be a randomized, placebo-controlled, parallel group, multicenter, Phase III study.The study aims to evaluate the Efficacy, Tolerability and Safety of Intramuscular Injections of PLX PAD for the Treatment of Subjects with Critical Limb Ischemia (CLI) with Minor Tissue Loss (Rutherford Category 5) who are Unsuitable for Revascularization.

Overall Status

Recruiting

Start Date

2017-05-22

Completion Date

2020-05-01

Primary Completion Date

2020-05-01

Phase

Phase 3

Study Type

Interventional

Primary Outcome

Measure	Time Frame
Time to major amputation or death (AFS)	Up to 36 months from enrollment

Secondary Outcome

Measure	Time Frame
Time to first occurrence of any of the events (in index leg)-major amputation,revascularization due to worsening of CLI,doubling of total wound area from baseline,anew gangrene. All-cause mortality.	Up to 36 months from enrollment
Time to major amputation of the index leg.	Up to 36 months from enrollment
Complete wound healing in the index leg	12 months from enrollment
Ischemic pain (NRS).	6 months from enrollment
Time to adjudicated major amputation of the index leg or death	Up to 36 months from enrollment

Enrollment

246

Condition

Critical Limb Ischemia (CLI)

Intervention

Intervention Type

Biological

Intervention Name

PLX-PAD

Description

Local intramuscular (IM) injections of PLX-PAD in the index leg.

Arm Group Label

PLX-PAD

Intervention Type

Biological

Intervention Name

Placebo

Description

Local intramuscular (IM) injections of Placebo in the index leg.

Arm Group Label

Placebo

Eligibility

Criteria

Inclusion Criteria: 1. Adult male or female subjects between ages 45-99 years of age. 2. CLI, with minor tissue loss up to the ankle level (Rutherford Category 5) 3. Ankle pressure (AP) ≤70 mmHg or TP ≤50 mmHg in the index leg. (If a subject has ABI >1.4 and TP is not measureable, inclusion may be based on TcPO2 ≤30 mmHg) 4. Subject unsuitable for revascularization (by any method) in the index leg. 5. Ischemic lesions in the index leg stable for at least 2 weeks. 6. Ischemic ulcers in the index leg without tendon or bone exposure (unless secondary to a minor amputation). 7. Under treatment for cardiovascular risk factors: hypertension, hyperlipidemia, diabetes, in accordance with applicable guidelines. Concomitant therapy with a statin and an anti-platelet agent for at least 2 weeks prior to randomization. 8. Women of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use at least one highly effective birth control method throughout the study. 9. Signed informed consent form. Exclusion Criteria: 1. Non-atherosclerotic PAD (e.g. Buerger's disease). 2. CLI with major tissue loss (Rutherford Category 6) in either leg. 3. Evidence of active infection (e.g., cellulitis, osteomyelitis). 4. Subject having undergone surgical revascularization or major amputation less than 1 month prior to screening, or endovascular revascularization or minor amputation less than 2 weeks prior to screening. 5. Planned or potential need for major/minor amputation or any revascularization within 1 month of study entry upon investigator's judgment. 6. Aorto-iliac stenosis or common femoral artery stenosis ≥70%, or otherwise suspicion of inadequate inflow to the leg. 7. Life expectancy of less than 6 months. 8. Stroke or acute myocardial infarction/unstable angina within 3 months prior to screening. 9. Severe congestive heart failure symptoms (New York Heart Association [NYHA] Stage IV). 10. Uncontrolled severe hypertension. 11. Diabetes mellitus with HbA1c >10%. 12. Current or history of proliferative retinopathy. 13. Known Hepatitis B virus or Hepatitis C virus or acquired immunodeficiency syndrome (AIDS) infections. 14. Subjects with international normalized ratio (INR) >2.5. 15. Subject on renal replacement therapy or with eGFR <15 mL/min/1.73m2. 16. Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending another investigational device or drug trial(s), unless in long-term follow-up phase. 17. Use of hyperbaric oxygen therapy, prostanoids, spinal cord stimulation, lumbar sympathectomy, wound dressing containing cells or growth factors, or topical platelet derived growth factor. 18. Known allergies to any of the following: DMSO, human serum albumin, bovine serum albumin. 19. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine. 20. Pulmonary disease requiring supplemental oxygen treatment on a daily basis. 21. Active malignancy or history of malignancy within 5 years prior to study entry. 22. In the opinion of the investigator, the subject is unsuitable for participating in the study. 23. Inability to understand and provide an informed consent.

Gender

All

Minimum Age

45 Years

Maximum Age

99 Years

Healthy Volunteers

Location

Facility	Status	Contact	Investigator
University of Miami Leonard M.Miller School of Medicine (UMMSM)-UHealth Pulmonary and Critical Care Medicine-Rosenstiel Building Location Miami Florida 33136-1015 United States	Recruiting	Last Name: Arash Bornak, MD Phone: 305-284-4093 Email: [email protected]	Last Name: Arash Bornak, MD Role: Principal Investigator
Tufts Medical Center (TMC) (Tufts-New England Medical Center) Boston Massachusetts 02111-1552 United States	Recruiting	Last Name: Mark Iafrati, MD Phone: 617-636-5019 Email: [email protected]	Last Name: Mark Iafrati, MD Role: Principal Investigator
Holy Medical Center Teaneck New Jersey 07666 United States	Recruiting	Last Name: John Rundback, Dr. Phone: 201-530-7967 Email: [email protected]
Mount Sinai St. Luke's hospital New York New York 10019-1147 United States	Recruiting	Last Name: John C Lantis, Dr. Phone: 212-523-5915 Email: [email protected]
Austin Heart Clinical Research Austin Texas 78756 United States	Recruiting	Last Name: Roger Gammon, MD Phone: 512-206-3600 Email: [email protected]	Last Name: Roger Gammon, MD Role: Principal Investigator
Department of Plastic Surgery ,Ut Southwestern Medical Center Dallas Texas 75390-9132 United States	Recruiting	Last Name: Lawrence Lavery, Dr. Phone: 214-786-5401 Email: [email protected]
Department of Internal Medicine Suppl. Leitung der Klin. Abteilung f. Angiologie Medizinische Universtitat Graz - Substitute Head of the Clinical Division of Angiology Graz A 8036 Austria	Recruiting	Last Name: Marianne Brodmann, MD Phone: 0043 31638513788 Email: [email protected]	Last Name: Marianne Brodmann, MD Role: Principal Investigator
UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery Burgas 8127 Bulgaria	Recruiting	Last Name: Galin Zhelev, Dr. Phone: +359 89 62 62 Email: [email protected]
MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology Sofia 1309 Bulgaria	Recruiting	Last Name: Mario Stankev, Prof. Phone: +359 2 822 31 36 Email: [email protected]
UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery Sofia 1431 Bulgaria	Recruiting	Last Name: Valentin Govedarski, Assoc. Prof. Phone: +359 888 242 418 Email: [email protected]
Cevni ambulance Hodonín 69501 Czechia	Recruiting	Last Name: Matuska Jiri Phone: 00420518341182 Email: [email protected]	Last Name: Matuska Jiri Role: Principal Investigator
Angiologicka ambulance Ostrava Dubina 700 30 Czechia	Recruiting	Last Name: Dusan Kucera, MD Phone: 00420 595633202 Email: [email protected]	Last Name: Dusan Kucera, MD Role: Principal Investigator
Vseobecna Fakultni Nemocnice v Praze Prague 12802 Czechia	Recruiting	Last Name: Jean-Claude Lubanda, MD Phone: 00420 774988566 Email: [email protected]	Last Name: Jean-Claude Lubanda, MD Role: Principal Investigator
Intitute of Clinical and Experimental Medicine Praha 4 140 21 Czechia	Recruiting	Last Name: Jaroslav Chlupac, MD Phone: 00420 737385657 Email: [email protected]	Last Name: Jaroslav Chlupac, MD Role: Principal Investigator
Krajska zdravotni a.s., Masarykova nemocnice o.z. Usti nad Labem 40113 Czechia	Recruiting	Last Name: Martin Sauer, MD Phone: 420 47 711 2504 Email: [email protected]	Last Name: Martin Sauer, MD Role: Principal Investigator
Universitats-Herzzentrum Freiburg Bad Krozingen 79189 Germany	Recruiting	Last Name: Thomas Zeller, MD Phone: 0049 76334022431 Email: [email protected]	Last Name: Thomas Zeller, MD Role: Principal Investigator
HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie Berlin 13125 Germany	Recruiting	Last Name: Peter Klein-Weigel, MD Phone: 30940154900 Email: [email protected]	Last Name: Peter Klein-Weigel Role: Principal Investigator
Franziskus-Krankenhaus Berlin Berlin Germany	Recruiting	Last Name: Berthold Amann, MD Phone: +493026386117 Email: [email protected]	Last Name: Berthold Amann, MD Role: Principal Investigator
Universitätsklinikum Carl Gustav Carus Dresden Germany	Not yet recruiting	Last Name: Norbert Weiss, MD Phone: +493514583659 Email: [email protected]	Last Name: Norbert Weiss, MD Role: Principal Investigator
Asklepios Klinik St.Georg-Angiologische Ambulanz Hamburg 20099 Germany	Recruiting	Last Name: Sigrid Nikol, Prof. Phone: 401818852401 Email: [email protected]	Last Name: Sigrid Nikol, Prof. Role: Principal Investigator
Universitaetsklinikum Muenster Muenster 48155 Germany	Recruiting	Last Name: Holger Reinecke, MD Phone: 0049 (0) 251 8346068 Email: [email protected]	Last Name: Holger Reinecke, MD Role: Principal Investigator
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Szekesfehervar Fejer 8000 Hungary	Recruiting	Last Name: Rudolf Menesi Phone: 0036209831112 Email: [email protected]	Last Name: Rudolf Menesi Role: Principal Investigator
Szent Imre Egyetemi Oktato Korhaz Budapest 1115 Hungary	Recruiting	Last Name: Katalin Farkas Phone: 0036 304648600 Email: [email protected]	Last Name: Katalin Farkas Role: Principal Investigator
Flor Ferenc County Hospital Kistarcsa 2143 Hungary	Recruiting	Last Name: Zsolt Pecsvarady, MD Phone: 0036 209458919 Email: [email protected]	Last Name: Zsolt Pecsvarady, MD Role: Principal Investigator
B-A-Z County and University Teaching Hospital Miskolc 3526 Hungary	Recruiting	Last Name: Lajos Matyas, MD Phone: 0036 646323694 Email: [email protected]	Last Name: Lajos Matyas, MD Role: Principal Investigator
Josa Andras Megyei Korhaz Nyíregyháza 4400 Hungary	Recruiting	Last Name: Geza Szabo Phone: 0036 42599700 Email: [email protected]	Last Name: Geza Szabo Role: Principal Investigator
Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School) Pecs 7624 Hungary	Recruiting	Last Name: Gabor Menyhei Phone: 0036 72 536 000 Email: [email protected]	Last Name: Gabor Menyhei Role: Principal Investigator
Acibadem Sistina Hospital,Thoracic and Vascular Surgery Skopje 1000 Macedonia, The Former Yugoslav Republic of	Recruiting	Last Name: Mitko Karagjozov, Prof. Phone: +389 2 3099 720 Email: [email protected]
Re-Medika General Hospital,Cardiovascular Surgery Skopje 1000 Macedonia, The Former Yugoslav Republic of	Recruiting	Last Name: Vlatko Cvetanovski, Dr. Phone: +389 2 2603 100 Email: [email protected]
Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery Skopje 1000 Macedonia, The Former Yugoslav Republic of	Recruiting	Last Name: Nikola Hristov, Dr. Phone: +389 (0)2 3091 500 Email: [email protected]
Szpital Uniwersytecki nr 1 im. dr. A. Jurasza Bydgoszcz 85094 Poland	Recruiting	Last Name: Arkadiusz Jawien Phone: 0048525854040 Email: [email protected]	Last Name: Arkadiusz Jawien Role: Principal Investigator
Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii Lublin 20-081 Poland	Recruiting	Last Name: Tomasz Zubilewicz, Prof. Phone: 0048 815325707 Email: [email protected]
Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie Szczecin 2359 Poland	Recruiting	Last Name: Piotr Gutowski, Prof. Phone: 0048 914661156 Email: [email protected]
Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego, Wrocław 51-124 Poland	Recruiting	Last Name: Wojciech Witkiewicz, Prof Phone: 0048 601703011 Email: [email protected]	Last Name: Wojciech Witkiewicz, Prof Role: Principal Investigator
Hull And East Yorkshire Women And Children's Hospital-Hull And East Yorkshire Hospitals Nhs Trust Hull HU32JZ United Kingdom	Recruiting	Last Name: George Edward Smith, MD Phone: 00441482675784 Email: [email protected]	Last Name: George Edward Smith, MD Role: Principal Investigator
Kings College Hospital London SE5 9RS United Kingdom	Recruiting	Last Name: Chris Manu, MD Phone: 0203 299 3704 Email: [email protected]	Last Name: Chris Manu, MD Role: Principal Investigator
Department of Vascular Research, St George's Hospital London SW17 0QT United Kingdom	Recruiting	Last Name: Ian Loftus, Prof. Phone: 0044 2086721255 Email: [email protected]

Location Countries

Country

Austria

Bulgaria

Czechia

Germany

Hungary

Macedonia, The Former Yugoslav Republic of

Poland

United Kingdom

United States

Verification Date

2018-03-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor

Has Expanded Access

Condition Browse

Ischemia

Number Of Arms

Arm Group

Arm Group Label

PLX-PAD

Arm Group Type

Experimental

Description

PLX-PAD will be administered via 30 IM injections (0.5 mL each). Each subject will be treated twice, with an interval of 8 weeks between treatments.

Arm Group Label

Placebo

Arm Group Type

Placebo Comparator

Description

Placebo will be administered via 30 IM injections (0.5 mL each). Each subject will be treated twice, with an interval of 8 weeks between treatments.

Firstreceived Results Date

N/A

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Double (Participant, Investigator)

Study First Submitted

December 27, 2016

Study First Submitted Qc

December 27, 2016

Study First Posted

December 30, 2016

Last Update Submitted

August 7, 2018

Last Update Submitted Qc

August 7, 2018

Last Update Posted

August 8, 2018

ClinicalTrials.gov processed this data on August 31, 2018

Conditions

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Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.

Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

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