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
- Conditions
- Critical Limb Ischemia (CLI)
- Interventions
- Biological: PLX-PADBiological: Placebo
- Registration Number
- NCT03006770
- Lead Sponsor
- Pluristem Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 213
- Adult male or female subjects between ages 45-99 years of age.
- CLI, with minor tissue loss up to the ankle level (Rutherford Category 5)
- 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)
- Subject unsuitable for revascularization (by any method) in the index leg.
- Ischemic lesions in the index leg stable for at least 2 weeks.
- Ischemic ulcers in the index leg without tendon or bone exposure (unless secondary to a minor amputation).
- 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.
- 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.
- Subject understood, agreed and provided informed consent. Patients must give written informed consent before any assessment is performed .
- Non-atherosclerotic PAD (e.g. Buerger's disease).
- CLI with major tissue loss (Rutherford Category 6) in either leg.
- Evidence of active infection (e.g., cellulitis, osteomyelitis).
- 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.
- Planned or potential need for major/minor amputation or any revascularization within 1 month of study entry upon investigator's judgment.
- Aorto-iliac stenosis or common femoral artery stenosis ≥70%, or otherwise suspicion of inadequate inflow to the leg.
- Life expectancy of less than 6 months.
- Stroke or acute myocardial infarction/unstable angina within 3 months prior to screening.
- Severe congestive heart failure symptoms (New York Heart Association [NYHA] class III-IV).
- Uncontrolled severe hypertension.
- Diabetes mellitus with HbA1c >10%.
- Current or history of proliferative retinopathy.
- Known Hepatitis B virus or Hepatitis C virus or acquired immunodeficiency syndrome (AIDS) infections.
- Subjects with international normalized ratio (INR) >2.
- Subject on renal replacement therapy or planned to start renal replacement therapy within 3 months of first screening visit.
- 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.
- Use of hyperbaric oxygen therapy, prostanoids, spinal cord stimulation, lumbar sympathectomy, wound dressing containing cells or growth factors, or topical platelet derived growth factor.
- Known allergies to any of the following: DMSO, human serum albumin, bovine serum albumin.
- History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine.
- Pulmonary disease requiring supplemental oxygen treatment on a daily basis.
- Active malignancy or history of malignancy within 5 years prior to study entry.
- In the opinion of the investigator, the subject is unsuitable for participating in the study.
- Chronic liver disease Child Pugh class B\C
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PLX-PAD PLX-PAD 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. Placebo Placebo 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.
- Primary Outcome Measures
Name Time Method Time to major amputation or death (AFS) Up to 36 months from enrollment
- Secondary Outcome Measures
Name Time Method Time to first occurrence of any of the events (in index leg)-major amputation, revascularization due to worsening of CLI, All-cause mortality. Up to 36 months from enrollment Time to major amputation of the index leg. Up to 36 months from enrollment Change from baseline in ischemic pain as assessed by numerical rating scale (NRS) at 6 months. 6 months from enrollment NRS measures the intensity or magnitude of sensations and subject feelings and the relative strength of attitudes and opinions about specific stimuli, on a scale of 0 to 10 with a score of zero denoting "no pain at all" and a score of 10 denoting "worst possible pain".
Proportion of subjects with complete healing of all ischemic lesions i.e., ulcers and necroses in the index leg at 12 months. 12 months from enrollment Time (days) from randomization to occurrence of death. Up to 36 months from enrollment
Trial Locations
- Locations (57)
UCI Medical Center 101 The City Drive S. Bldg 55 Rm 334 Orange, CA 92868
🇺🇸Irvine, California, United States
Cedars Sinai Medical Center,LA,Beverly Hills,8536 Wilshire Boulevard, Third Floor
🇺🇸Los Angeles, California, United States
Room S3-746, Dept of Surgery, UMASS Medical School, 55 Lake Ave North.
🇺🇸Worcester, Massachusetts, United States
Tufts Medical Center (TMC) (Tufts-New England Medical Center)
🇺🇸Boston, Massachusetts, United States
Department of Plastic Surgery ,Ut Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Holy Medical Center
🇺🇸Teaneck, New Jersey, United States
Austin Heart Clinical Research
🇺🇸Austin, Texas, United States
Mount Sinai St. Luke's hospital
🇺🇸New York, New York, United States
Northwell Health Comprehensive Wound Healing Center
🇺🇸Lake Success, New York, United States
UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery
🇧🇬Burgas, Bulgaria
MHAT Sveti Nokolay Chudotvorets EOOD - Lom,Surgery Department,Address 2, Todor Kableshkov str.
🇧🇬Lom, Bulgaria
UMHAT "St. Georgi" EAD,Clinic: Vascular Surgery and Angiology 66 "Peshtersko Shosse" Blvd., 8th floor, Hirurgicheski blok
🇧🇬Plovdiv, Bulgaria
UMBAL Kanev AD - Ruse,Department of Vascular Surgery Address: 2, Nezavisimost str
🇧🇬Ruse, Bulgaria
MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology
🇧🇬Sofia, Bulgaria
Acibadem City Clinic MHAT Tokuda, Vascular Surgery and Angiology 51B "Nikola Vaptzarov" Blvd
🇧🇬Sofia, Bulgaria
UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery
🇧🇬Sofia, Bulgaria
Cevni ambulance
🇨🇿Hodonín, Czechia
Angiologicka ambulance
🇨🇿Ostrava Dubina, Czechia
UMHAT "Medica" Ruse Department of Vascular Surgery 35, "Riga", Str Post code: 7013 Ruse, Bulgaria
🇧🇬Ruse, Bulgaria
Vseobecna Fakultni Nemocnice v Praze
🇨🇿Prague, Czechia
Intitute of Clinical and Experimental Medicine
🇨🇿Praha 4, Czechia
Krajska zdravotni a.s., Masarykova nemocnice o.z.
🇨🇿Usti nad Labem, Czechia
Medinos Klinikum Sonneberg Abteilung für Kardiologie/Angiologie - Studienambulanz Neustadter Straße 61 96515 Sonneberg Germany
🇩🇪Sonneberg, Thueringen, Germany
Universitats-Herzzentrum Freiburg
🇩🇪Bad Krozingen, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Heinrich-Heine-Universitaet Duesseldorf - Universitaetsklinikum Duesseldorf (UKD)
🇩🇪Duesseldorf, Germany
Klinik und Poliklinik für Angiologie Universitätsklinikum Leipzig AöR Liebigstr. 20 04103 Leipzig, Germany
🇩🇪Leipzig, Saxony, Germany
Charite Centrum fur Herz - Kreislauf - und Gefassmedizin - Campus Benjamin Franklin
🇩🇪Berlin, Germany
HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie
🇩🇪Berlin, Germany
Asklepios Klinik St.Georg-Angiologische Ambulanz
🇩🇪Hamburg, Germany
Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany
🇩🇪Kösching, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
🇭🇺Szekesfehervar, Fejer, Hungary
Szent Imre Egyetemi Oktato Korhaz
🇭🇺Budapest, Hungary
Flor Ferenc County Hospital
🇭🇺Kistarcsa, Hungary
B-A-Z County and University Teaching Hospital
🇭🇺Miskolc, Hungary
Josa Andras Megyei Korhaz
🇭🇺Nyíregyháza, Hungary
Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)
🇭🇺Pecs, Hungary
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Blood Vessel Day Care at Clalit Community Horev Center, Horev Center
🇮🇱Haifa, Israel
Vascular Surgery Department, Hadassah Ein Karem MC
🇮🇱Jerusalem, Israel
Re-Medika General Hospital,Cardiovascular Surgery
🇲🇰Skopje, North Macedonia
Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery
🇲🇰Skopje, North Macedonia
Vascular Surgery Department Rabin Medical Center Beilinson Hospital, 39 Jabotinski St. Petah Tikva Israel 4941492
🇮🇱Petah Tikva, Israel
Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii
🇵🇱Lublin, Poland
The Cardiological Department, The Baruch Padeh Medical Center
🇮🇱Poriyya 'Illit, Israel
Acibadem Sistina Hospital,Thoracic and Vascular Surgery
🇲🇰Skopje, North Macedonia
Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego,
🇵🇱Wrocław, Poland
Vascular Research Clinical Research Centre Beaufort Way Southmead Hospital Westbury on Trym Bristol
🇬🇧Bristol, United Kingdom
Department of Vascular Research, St George's Hospital
🇬🇧London, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Hull And East Yorkshire Women And Children's Hospital-Hull And East Yorkshire Hospitals Nhs Trust
🇬🇧Hull, United Kingdom
Vascular Center ∣ Department of Surgery ∣ UC Davis Health 4860 Y street, Sacramento, CA suite #3400, 95817
🇺🇸Sacramento, California, United States
Vascular Center,Department of Surgery,UC Davis Health,4860 Y street
🇺🇸Sacramento, California, United States
University of Miami Leonard M.Miller School of Medicine (UMMSM)-UHealth Pulmonary and Critical Care Medicine-Rosenstiel Building Location
🇺🇸Miami, Florida, United States
Miami Cardiac and Vascular Institute Baptist Health South Florida
🇺🇸Miami, Florida, United States
Duke University Medical Center,Durham,2424 Erwin Road Hock Plaza
🇺🇸Durham, North Carolina, United States