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
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
Sponsors
Source
Pluristem Ltd.
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
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
Intervention
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
No
Location
Facility |
Status |
Contact |
Investigator |
UCI Medical Center 101 The City Drive S. Bldg 55 Rm 334 Orange, CA 92868 Irvine California 92697 United States |
Recruiting |
Last Name: Isabella Kuo, Dr. Role: Principal Investigator | |
Cedars Sinai Medical Center,LA,Beverly Hills,8536 Wilshire Boulevard, Third Floor Los Angeles California 90211 United States |
Recruiting |
Last Name: Suhail Dohad, Dr Role: Principal Investigator | |
Vascular Center ∣ Department of Surgery ∣ UC Davis Health 4860 Y street, Sacramento, CA suite #3400, 95817 Sacramento California 95817 United States |
Recruiting |
Last Name: Nasim Hedayati, Dr. Role: Principal Investigator | |
Vascular Center,Department of Surgery,UC Davis Health,4860 Y street Sacramento California 95817 United States |
Recruiting |
Last Name: Nasim Hedayati, Dr. Role: Principal 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 Role: Principal Investigator | |
Tufts Medical Center (TMC) (Tufts-New England Medical Center) Boston Massachusetts 02111-1552 United States |
Recruiting |
Last Name: Mark Iafrati, MD Role: Principal Investigator | |
Room S3-746, Dept of Surgery, UMASS Medical School, 55 Lake Ave North. Worcester Massachusetts 01655 United States |
Recruiting |
Last Name: Andres Schanzer, Dr. Role: Principal Investigator | |
Holy Medical Center Teaneck New Jersey 07666 United States |
Recruiting | ||
Mount Sinai St. Luke's hospital New York New York 10019-1147 United States |
Recruiting | ||
Duke University Medical Center,Durham,2424 Erwin Road Hock Plaza Durham North Carolina 27710 United States |
Recruiting |
Last Name: William Schuyler Jones, Dr Role: Principal Investigator | |
Austin Heart Clinical Research Austin Texas 78756 United States |
Recruiting |
Last Name: Roger Gammon, MD Role: Principal Investigator | |
Department of Plastic Surgery ,Ut Southwestern Medical Center Dallas Texas 75390-9132 United States |
Recruiting | ||
UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery Burgas 8127 Bulgaria |
Recruiting | ||
MHAT Sveti Nokolay Chudotvorets EOOD - Lom,Surgery Department,Address 2, Todor Kableshkov str. Lom 3600 Bulgaria |
Recruiting |
Last Name: Iliyan Petrov, Dr. Role: Principal Investigator | |
UMHAT "St. Georgi" EAD,Clinic: Vascular Surgery and Angiology 66 "Peshtersko Shosse" Blvd., 8th floor, Hirurgicheski blok Plovdiv 4001 Bulgaria |
Recruiting |
Last Name: Drago Zhelev, Assoc. Prof. Role: Principal Investigator | |
UMBAL Kanev AD - Ruse,Department of Vascular Surgery Address: 2, Nezavisimost str Ruse 7002 Bulgaria |
Recruiting |
Last Name: Georgi Georgiev, Dr. Role: Principal Investigator | |
UMHAT "Medica" Ruse Department of Vascular Surgery 35, "Riga", Str Post code: 7013 Ruse, Bulgaria Ruse 7013 Bulgaria |
Recruiting |
Last Name: Hristo Georgiev, Dr. Role: Principal Investigator | |
MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology Sofia 1309 Bulgaria |
Recruiting | ||
Acibadem City Clinic MHAT Tokuda, Vascular Surgery and Angiology 51B "Nikola Vaptzarov" Blvd Sofia 1407 Bulgaria |
Recruiting |
Last Name: Vasil Chervenkov, Prof. Role: Principal Investigator | |
UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery Sofia 1431 Bulgaria |
Recruiting | ||
Cevni ambulance Hodonín 69501 Czechia |
Recruiting |
Last Name: Matuska Jiri Role: Principal Investigator | |
Angiologicka ambulance Ostrava Dubina 700 30 Czechia |
Recruiting |
Last Name: Dusan Kucera, MD Role: Principal Investigator | |
Vseobecna Fakultni Nemocnice v Praze Prague 12802 Czechia |
Recruiting |
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 Role: Principal Investigator | |
Krajska zdravotni a.s., Masarykova nemocnice o.z. Usti nad Labem 40113 Czechia |
Recruiting |
Last Name: Martin Sauer, MD Role: Principal Investigator | |
Klinik und Poliklinik für Angiologie Universitätsklinikum Leipzig AöR Liebigstr. 20 04103 Leipzig, Germany Leipzig Saxony 04103 Germany |
Recruiting |
Last Name: Andrej Schmidt, Dr. Role: Principal Investigator | |
Medinos Klinikum Sonneberg Abteilung für Kardiologie/Angiologie - Studienambulanz Neustadter Straße 61 96515 Sonneberg Germany Sonneberg Thueringen 96515 Germany |
Recruiting |
Last Name: Marcus Thieme, Dr. Role: Principal Investigator | |
Universitats-Herzzentrum Freiburg Bad Krozingen 79189 Germany |
Recruiting |
Last Name: Thomas Zeller, MD Role: Principal Investigator | |
Charite Centrum fur Herz - Kreislauf - und Gefassmedizin - Campus Benjamin Franklin Berlin 12203 Germany |
Recruiting |
Last Name: Ursula Rauch, Dr. Role: Principal Investigator | |
HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie Berlin 13125 Germany |
Recruiting |
Last Name: Peter Klein-Weigel Role: Principal Investigator | |
Franziskus-Krankenhaus Berlin Berlin Germany |
Withdrawn | ||
Universitätsklinikum Carl Gustav Carus Dresden Germany |
Recruiting |
Last Name: Norbert Weiss, MD Role: Principal Investigator | |
Heinrich-Heine-Universitaet Duesseldorf - Universitaetsklinikum Duesseldorf (UKD) Duesseldorf 40225 Germany |
Recruiting |
Last Name: Hubert Schelzig, Prof. Role: Principal Investigator | |
Asklepios Klinik St.Georg-Angiologische Ambulanz Hamburg 20099 Germany |
Recruiting |
Last Name: Sigrid Nikol, Prof. Role: Principal Investigator | |
Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany Kösching 85092 Germany |
Recruiting |
Last Name: Alexander Hansen, Prof. Role: Principal Investigator | |
Universitaetsklinikum Muenster Muenster 48155 Germany |
Recruiting |
Last Name: Holger Reinecke, MD Role: Principal Investigator | |
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Szekesfehervar Fejer 8000 Hungary |
Recruiting |
Last Name: Rudolf Menesi Role: Principal Investigator | |
Szent Imre Egyetemi Oktato Korhaz Budapest 1115 Hungary |
Recruiting |
Last Name: Katalin Farkas Role: Principal Investigator | |
Flor Ferenc County Hospital Kistarcsa 2143 Hungary |
Recruiting |
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 Role: Principal Investigator | |
Josa Andras Megyei Korhaz Nyíregyháza 4400 Hungary |
Recruiting |
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 Role: Principal Investigator | |
Vascular Surgery Department, Hadassah Ein Karem MC Jerusalem 91120 Israel |
Recruiting |
Last Name: Asaf Rabin, Dr. Role: Principal Investigator | |
Vascular Surgery Department Rabin Medical Center Beilinson Hospital, 39 Jabotinski St. Petah Tikva Israel 4941492 Petah Tikva 4941492 Israel |
Recruiting |
Last Name: Galit Sivak, Dr. Role: Principal Investigator | |
The Cardiological Department, The Baruch Padeh Medical Center Poriya 15208 Israel |
Recruiting |
Last Name: Diab Ghanem, Dr. Role: Principal Investigator | |
Acibadem Sistina Hospital,Thoracic and Vascular Surgery Skopje 1000 North Macedonia |
Recruiting | ||
Re-Medika General Hospital,Cardiovascular Surgery Skopje 1000 North Macedonia |
Recruiting | ||
Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery Skopje 1000 North Macedonia |
Recruiting | ||
Szpital Uniwersytecki nr 1 im. dr. A. Jurasza Bydgoszcz 85094 Poland |
Withdrawn | ||
Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii Lublin 20-081 Poland |
Recruiting | ||
Samodzielny Publiczny Szpital Kliniczny Nr 2 Pomorskiego Uniwersytetu Medycznego w Szczecinie Szczecin 2359 Poland |
Withdrawn | ||
Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego, Wrocław 51-124 Poland |
Recruiting |
Last Name: Wojciech Witkiewicz, Prof Role: Principal Investigator | |
Vascular Research Clinical Research Centre Beaufort Way Southmead Hospital Westbury on Trym Bristol Bristol BS10 5NB United Kingdom |
Recruiting |
Last Name: Robert Hinchliffe, Dr. 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 Role: Principal Investigator | |
Kings College Hospital London SE5 9RS United Kingdom |
Recruiting |
Last Name: Chris Manu, MD Role: Principal Investigator | |
Department of Vascular Research, St George's Hospital London SW17 0QT United Kingdom |
Recruiting |
Location Countries
Country
Bulgaria
Czechia
Germany
Hungary
Israel
North Macedonia
Poland
United Kingdom
United States
Verification Date
2019-04-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Number Of Arms
2
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
Removed Countries
Country
Austria
Macedonia, The Former Yugoslav Republic of
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
November 14, 2019
Last Update Submitted Qc
November 14, 2019
Last Update Posted
November 15, 2019
ClinicalTrials.gov processed this data on December 06, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
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.
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.