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

NCT ID: NCT03006770

Last Updated: 2024-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

213 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-22

Study Completion Date

2022-04-20

Brief Summary

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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

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Conditions

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Critical Limb Ischemia (CLI)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

PLX-PAD

Intervention Type BIOLOGICAL

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

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

Interventions

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PLX-PAD

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

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

45 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pluristem Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCI Medical Center 101 The City Drive S. Bldg 55 Rm 334 Orange, CA 92868

Irvine, California, United States

Site Status

Cedars Sinai Medical Center,LA,Beverly Hills,8536 Wilshire Boulevard, Third Floor

Los Angeles, California, United States

Site Status

Vascular Center ∣ Department of Surgery ∣ UC Davis Health 4860 Y street, Sacramento, CA suite #3400, 95817

Sacramento, California, United States

Site Status

Vascular Center,Department of Surgery,UC Davis Health,4860 Y street

Sacramento, California, United States

Site Status

University of Miami Leonard M.Miller School of Medicine (UMMSM)-UHealth Pulmonary and Critical Care Medicine-Rosenstiel Building Location

Miami, Florida, United States

Site Status

Miami Cardiac and Vascular Institute Baptist Health South Florida

Miami, Florida, United States

Site Status

Tufts Medical Center (TMC) (Tufts-New England Medical Center)

Boston, Massachusetts, United States

Site Status

Room S3-746, Dept of Surgery, UMASS Medical School, 55 Lake Ave North.

Worcester, Massachusetts, United States

Site Status

Holy Medical Center

Teaneck, New Jersey, United States

Site Status

Northwell Health Comprehensive Wound Healing Center

Lake Success, New York, United States

Site Status

Mount Sinai St. Luke's hospital

New York, New York, United States

Site Status

Duke University Medical Center,Durham,2424 Erwin Road Hock Plaza

Durham, North Carolina, United States

Site Status

Austin Heart Clinical Research

Austin, Texas, United States

Site Status

Department of Plastic Surgery ,Ut Southwestern Medical Center

Dallas, Texas, United States

Site Status

UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery

Burgas, , Bulgaria

Site Status

MHAT Sveti Nokolay Chudotvorets EOOD - Lom,Surgery Department,Address 2, Todor Kableshkov str.

Lom, , Bulgaria

Site Status

UMHAT "St. Georgi" EAD,Clinic: Vascular Surgery and Angiology 66 "Peshtersko Shosse" Blvd., 8th floor, Hirurgicheski blok

Plovdiv, , Bulgaria

Site Status

UMBAL Kanev AD - Ruse,Department of Vascular Surgery Address: 2, Nezavisimost str

Rousse, , Bulgaria

Site Status

UMHAT "Medica" Ruse Department of Vascular Surgery 35, "Riga", Str Post code: 7013 Ruse, Bulgaria

Rousse, , Bulgaria

Site Status

MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology

Sofia, , Bulgaria

Site Status

Acibadem City Clinic MHAT Tokuda, Vascular Surgery and Angiology 51B "Nikola Vaptzarov" Blvd

Sofia, , Bulgaria

Site Status

UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery

Sofia, , Bulgaria

Site Status

Cevni ambulance

Hodonín, , Czechia

Site Status

Angiologicka ambulance

Ostrava Dubina, , Czechia

Site Status

Vseobecna Fakultni Nemocnice v Praze

Prague, , Czechia

Site Status

Intitute of Clinical and Experimental Medicine

Prague, , Czechia

Site Status

Krajska zdravotni a.s., Masarykova nemocnice o.z.

Ústí nad Labem, , Czechia

Site Status

Klinik und Poliklinik für Angiologie Universitätsklinikum Leipzig AöR Liebigstr. 20 04103 Leipzig, Germany

Leipzig, Saxony, Germany

Site Status

Medinos Klinikum Sonneberg Abteilung für Kardiologie/Angiologie - Studienambulanz Neustadter Straße 61 96515 Sonneberg Germany

Sonneberg, Thuringia, Germany

Site Status

Universitats-Herzzentrum Freiburg

Bad Krozingen, , Germany

Site Status

Charite Centrum fur Herz - Kreislauf - und Gefassmedizin - Campus Benjamin Franklin

Berlin, , Germany

Site Status

HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie

Berlin, , Germany

Site Status

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status

Heinrich-Heine-Universitaet Duesseldorf - Universitaetsklinikum Duesseldorf (UKD)

Düsseldorf, , Germany

Site Status

Asklepios Klinik St.Georg-Angiologische Ambulanz

Hamburg, , Germany

Site Status

Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany

Kösching, , Germany

Site Status

Universitaetsklinikum Muenster

Münster, , Germany

Site Status

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, Fejér, Hungary

Site Status

Szent Imre Egyetemi Oktato Korhaz

Budapest, , Hungary

Site Status

Flor Ferenc County Hospital

Kistarcsa, , Hungary

Site Status

B-A-Z County and University Teaching Hospital

Miskolc, , Hungary

Site Status

Josa Andras Megyei Korhaz

Nyíregyháza, , Hungary

Site Status

Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)

Pécs, , Hungary

Site Status

Barzilai Medical Center

Ashkelon, , Israel

Site Status

Blood Vessel Day Care at Clalit Community Horev Center, Horev Center

Haifa, , Israel

Site Status

Vascular Surgery Department, Hadassah Ein Karem MC

Jerusalem, , Israel

Site Status

Vascular Surgery Department Rabin Medical Center Beilinson Hospital, 39 Jabotinski St. Petah Tikva Israel 4941492

Petah Tikva, , Israel

Site Status

The Cardiological Department, The Baruch Padeh Medical Center

Poria Illit, , Israel

Site Status

Acibadem Sistina Hospital,Thoracic and Vascular Surgery

Skopje, , North Macedonia

Site Status

Re-Medika General Hospital,Cardiovascular Surgery

Skopje, , North Macedonia

Site Status

Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery

Skopje, , North Macedonia

Site Status

Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii

Lublin, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego,

Wroclaw, , Poland

Site Status

Vascular Research Clinical Research Centre Beaufort Way Southmead Hospital Westbury on Trym Bristol

Bristol, , United Kingdom

Site Status

Hull And East Yorkshire Women And Children's Hospital-Hull And East Yorkshire Hospitals Nhs Trust

Hull, , United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

Department of Vascular Research, St George's Hospital

London, , United Kingdom

Site Status

Countries

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United States Bulgaria Czechia Germany Hungary Israel North Macedonia Poland United Kingdom

References

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Norgren L, Weiss N, Nikol S, Lantis JC, Patel MR, Hinchliffe RJ, Reinecke H, Volk HD, Reinke P, Fadini GP, Ofir R, Rothenstein D, Halevy N, Karagjozov M, Rundback JH. PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial. Br J Surg. 2024 Jan 31;111(2):znad437. doi: 10.1093/bjs/znad437.

Reference Type DERIVED
PMID: 38294084 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30686676 (View on PubMed)

Other Identifiers

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PLX-CLI-03

Identifier Type: -

Identifier Source: org_study_id

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