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

Critical Limb Ischemia (CLI) Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03006770
• Other study ID #: PLX-CLI-03
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 22, 2017
• Est. completion date: March 2021

Study information

• Verified date: December 2020
• Source: Pluristem Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 213
• Est. completion date: March 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Limb Ischemia (CLI)
• Ischemia

Intervention

Biological:
• PLX-PAD
Local intramuscular (IM) injections of PLX-PAD in the index leg.
• Placebo
Local intramuscular (IM) injections of Placebo in the index leg.

Locations

Country	Name	City	State
Bulgaria	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	UMHAT "Medica" Ruse Department of Vascular Surgery 35, "Riga", Str Post code: 7013 Ruse, Bulgaria	Ruse
Bulgaria	Acibadem City Clinic MHAT Tokuda, Vascular Surgery and Angiology 51B "Nikola Vaptzarov" Blvd	Sofia
Bulgaria	MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology	Sofia
Bulgaria	UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery	Sofia
Czechia	Cevni ambulance	Hodonín
Czechia	Angiologicka ambulance	Ostrava Dubina
Czechia	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
Germany	Universitats-Herzzentrum Freiburg	Bad Krozingen
Germany	Charite Centrum fur Herz - Kreislauf - und Gefassmedizin - Campus Benjamin Franklin	Berlin
Germany	HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie	Berlin
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Heinrich-Heine-Universitaet Duesseldorf - Universitaetsklinikum Duesseldorf (UKD)	Duesseldorf
Germany	Asklepios Klinik St.Georg-Angiologische Ambulanz	Hamburg
Germany	Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany	Kösching
Germany	Klinik und Poliklinik für Angiologie Universitätsklinikum Leipzig AöR Liebigstr. 20 04103 Leipzig, Germany	Leipzig	Saxony
Germany	Universitaetsklinikum Muenster	Muenster
Germany	Medinos Klinikum Sonneberg Abteilung für Kardiologie/Angiologie - Studienambulanz Neustadter Straße 61 96515 Sonneberg Germany	Sonneberg	Thueringen
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	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar	Fejer
Israel	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	Vascular Surgery Department Rabin Medical Center Beilinson Hospital, 39 Jabotinski St. Petah Tikva Israel 4941492	Petah Tikva
Israel	The Cardiological Department, The Baruch Padeh Medical Center	Poriyya 'Illit
North Macedonia	Acibadem Sistina Hospital,Thoracic and Vascular Surgery	Skopje
North Macedonia	Re-Medika General Hospital,Cardiovascular Surgery	Skopje
North Macedonia	Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery	Skopje
Poland	Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii	Lublin
Poland	Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego,	Wroclaw
United Kingdom	Vascular Research Clinical Research Centre Beaufort Way Southmead Hospital Westbury on Trym Bristol	Bristol
United Kingdom	Hull And East Yorkshire Women And Children's Hospital-Hull And East Yorkshire Hospitals Nhs Trust	Hull
United Kingdom	Department of Vascular Research, St George's Hospital	London
United Kingdom	Kings College Hospital	London
United States	Austin Heart Clinical Research	Austin	Texas
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	Duke University Medical Center,Durham,2424 Erwin Road Hock Plaza	Durham	North Carolina
United States	UCI Medical Center 101 The City Drive S. Bldg 55 Rm 334 Orange, CA 92868	Irvine	California
United States	Northwell Health Comprehensive Wound Healing Center	Lake Success	New York
United States	Cedars Sinai Medical Center,LA,Beverly Hills,8536 Wilshire Boulevard, Third Floor	Los Angeles	California
United States	Miami Cardiac and Vascular Institute Baptist Health South Florida	Miami	Florida
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	Mount Sinai St. Luke's hospital	New York	New York
United States	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	Holy Medical Center	Teaneck	New Jersey
United States	Room S3-746, Dept of Surgery, UMASS Medical School, 55 Lake Ave North.	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pluristem Ltd.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to major amputation or death (AFS)		Up to 36 months from enrollment
Secondary	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
Secondary	Time to major amputation of the index leg.		Up to 36 months from enrollment
Secondary	Change from baseline in ischemic pain as assessed by numerical rating scale (NRS) at 6 months.	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".	6 months from enrollment
Secondary	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
Secondary	Time (days) from randomization to occurrence of death.		Up to 36 months from enrollment