Clinical trial NCT03006770: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Critical Limb Ischemia (CLI)
Lead sponsor: Pluristem Ltd.
Sponsor class: INDUSTRY
First posted: 2016-12-30
Enrollment: 213
Sex: ALL
Minimum age (years): 45
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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. Subject understood, agreed and provided informed consent. Patients must give written informed consent before any assessment is performed .

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 \[NYHA\] class III-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.
15. Subject on renal replacement therapy or planned to start renal replacement therapy within 3 months of first screening visit.
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. Chronic liver disease Child Pugh class B\\C

Primary outcomes:
measure: Time to major amputation or death (AFS)
timeFrame: Up to 36 months from enrollment
Secondary outcomes:
measure: Time to first occurrence of any of the events (in index leg)-major amputation, revascularization due to worsening of CLI, All-cause mortality.
timeFrame: Up to 36 months from enrollment
measure: Time to major amputation of the index leg.
timeFrame: Up to 36 months from enrollment
measure: Change from baseline in ischemic pain as assessed by numerical rating scale (NRS) at 6 months.
timeFrame: 6 months from enrollment
measure: Proportion of subjects with complete healing of all ischemic lesions i.e., ulcers and necroses in the index leg at 12 months.
timeFrame: 12 months from enrollment
measure: Time (days) from randomization to occurrence of death.
timeFrame: Up to 36 months from enrollment
Other outcomes:
Locations:
city: Irvine
country: United States
facility: UCI Medical Center 101 The City Drive S. Bldg 55 Rm 334 Orange, CA 92868
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center,LA,Beverly Hills,8536 Wilshire Boulevard, Third Floor
state: California
city: Sacramento
country: United States
facility: Vascular Center ∣ Department of Surgery ∣ UC Davis Health 4860 Y street, Sacramento, CA suite #3400, 95817
state: California
city: Sacramento
country: United States
facility: Vascular Center,Department of Surgery,UC Davis Health,4860 Y street
state: California
city: Miami
country: United States
facility: University of Miami Leonard M.Miller School of Medicine (UMMSM)-UHealth Pulmonary and Critical Care Medicine-Rosenstiel Building Location
state: Florida
city: Miami
country: United States
facility: Miami Cardiac and Vascular Institute Baptist Health South Florida
state: Florida
city: Boston
country: United States
facility: Tufts Medical Center (TMC) (Tufts-New England Medical Center)
state: Massachusetts
city: Worcester
country: United States
facility: Room S3-746, Dept of Surgery, UMASS Medical School, 55 Lake Ave North.
state: Massachusetts
city: Teaneck
country: United States
facility: Holy Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health Comprehensive Wound Healing Center
state: New York
city: New York
country: United States
facility: Mount Sinai St. Luke's hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center,Durham,2424 Erwin Road Hock Plaza
state: North Carolina
city: Austin
country: United States
facility: Austin Heart Clinical Research
state: Texas
city: Dallas
country: United States
facility: Department of Plastic Surgery ,Ut Southwestern Medical Center
state: Texas
city: Burgas
country: Bulgaria
facility: UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery
city: Lom
country: Bulgaria
facility: MHAT Sveti Nokolay Chudotvorets EOOD - Lom,Surgery Department,Address 2, Todor Kableshkov str.
city: Plovdiv
country: Bulgaria
facility: UMHAT "St. Georgi" EAD,Clinic: Vascular Surgery and Angiology 66 "Peshtersko Shosse" Blvd., 8th floor, Hirurgicheski blok
city: Ruse
country: Bulgaria
facility: UMBAL Kanev AD - Ruse,Department of Vascular Surgery Address: 2, Nezavisimost str
city: Ruse
country: Bulgaria
facility: UMHAT "Medica" Ruse Department of Vascular Surgery 35, "Riga", Str Post code: 7013 Ruse, Bulgaria
city: Sofia
country: Bulgaria
facility: MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic MHAT Tokuda, Vascular Surgery and Angiology 51B "Nikola Vaptzarov" Blvd
city: Sofia
country: Bulgaria
facility: UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery
city: Hodonín
country: Czechia
facility: Cevni ambulance
city: Ostrava Dubina
country: Czechia
facility: Angiologicka ambulance
city: Prague
country: Czechia
facility: Vseobecna Fakultni Nemocnice v Praze
city: Praha 4
country: Czechia
facility: Intitute of Clinical and Experimental Medicine
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni a.s., Masarykova nemocnice o.z.
city: Leipzig
country: Germany
facility: Klinik und Poliklinik für Angiologie Universitätsklinikum Leipzig AöR Liebigstr. 20 04103 Leipzig, Germany
state: Saxony
city: Sonneberg
country: Germany
facility: Medinos Klinikum Sonneberg Abteilung für Kardiologie/Angiologie - Studienambulanz Neustadter Straße 61 96515 Sonneberg Germany
state: Thueringen
city: Bad Krozingen
country: Germany
facility: Universitats-Herzzentrum Freiburg
city: Berlin
country: Germany
facility: Charite Centrum fur Herz - Kreislauf - und Gefassmedizin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Heinrich-Heine-Universitaet Duesseldorf - Universitaetsklinikum Duesseldorf (UKD)
city: Hamburg
country: Germany
facility: Asklepios Klinik St.Georg-Angiologische Ambulanz
city: Kösching
country: Germany
facility: Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
state: Fejer
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktato Korhaz
city: Kistarcsa
country: Hungary
facility: Flor Ferenc County Hospital
city: Miskolc
country: Hungary
facility: B-A-Z County and University Teaching Hospital
city: Nyíregyháza
country: Hungary
facility: Josa Andras Megyei Korhaz
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Blood Vessel Day Care at Clalit Community Horev Center, Horev Center
city: Jerusalem
country: Israel
facility: Vascular Surgery Department, Hadassah Ein Karem MC
city: Petah Tikva
country: Israel
facility: Vascular Surgery Department Rabin Medical Center Beilinson Hospital, 39 Jabotinski St. Petah Tikva Israel 4941492
city: Poriyya 'Illit
country: Israel
facility: The Cardiological Department, The Baruch Padeh Medical Center
city: Skopje
country: North Macedonia
facility: Acibadem Sistina Hospital,Thoracic and Vascular Surgery
city: Skopje
country: North Macedonia
facility: Re-Medika General Hospital,Cardiovascular Surgery
city: Skopje
country: North Macedonia
facility: Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery
city: Lublin
country: Poland
facility: Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii
city: Wrocław
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego,
city: Bristol
country: United Kingdom
facility: Vascular Research Clinical Research Centre Beaufort Way Southmead Hospital Westbury on Trym Bristol
city: Hull
country: United Kingdom
facility: Hull And East Yorkshire Women And Children's Hospital-Hull And East Yorkshire Hospitals Nhs Trust
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Department of Vascular Research, St George's Hospital
Study officials:
References:
citation: Norgren L, Weiss N, Nikol S, Hinchliffe RJ, Lantis JC, Patel MR, Reinecke H, Ofir R, Rosen Y, Peres D, Aberman Z. PLX-PAD Cell Treatment of Critical Limb Ischaemia: Rationale and Design of the PACE Trial. Eur J Vasc Endovasc Surg. 2019 Apr;57(4):538-545. doi: 10.1016/j.ejvs.2018.11.008. Epub 2019 Jan 25.