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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

Sponsor
Pluristem Ltd. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03006770
Collaborator
(none)
213
Enrollment
57
Locations
2
Arms
45.3
Anticipated Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: PLX-PAD
  • Biological: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
213 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 22, 2017
Anticipated Primary Completion Date :
Mar 1, 2021
Anticipated Study Completion Date :
Mar 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

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

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

Outcome Measures

Primary Outcome Measures

  1. Time to major amputation or death (AFS) [Up to 36 months from enrollment]

Secondary Outcome Measures

  1. 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]

  2. Time to major amputation of the index leg. [Up to 36 months from enrollment]

  3. 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".

  4. 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]

  5. Time (days) from randomization to occurrence of death. [Up to 36 months from enrollment]

Eligibility Criteria

Criteria

Ages Eligible for Study:
45 Years to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

  1. Subject unsuitable for revascularization (by any method) in the index leg.

  2. Ischemic lesions in the index leg stable for at least 2 weeks.

  3. Ischemic ulcers in the index leg without tendon or bone exposure (unless secondary to a minor amputation).

  4. 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.

  5. 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.

  6. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 UCI Medical Center 101 The City Drive S. Bldg 55 Rm 334 Orange, CA 92868 Irvine California United States 92697
2 Cedars Sinai Medical Center,LA,Beverly Hills,8536 Wilshire Boulevard, Third Floor Los Angeles California United States 90211
3 Vascular Center ∣ Department of Surgery ∣ UC Davis Health 4860 Y street, Sacramento, CA suite #3400, 95817 Sacramento California United States 95817
4 Vascular Center,Department of Surgery,UC Davis Health,4860 Y street Sacramento California United States 95817
5 University of Miami Leonard M.Miller School of Medicine (UMMSM)-UHealth Pulmonary and Critical Care Medicine-Rosenstiel Building Location Miami Florida United States 33136-1015
6 Miami Cardiac and Vascular Institute Baptist Health South Florida Miami Florida United States 33176
7 Tufts Medical Center (TMC) (Tufts-New England Medical Center) Boston Massachusetts United States 02111-1552
8 Room S3-746, Dept of Surgery, UMASS Medical School, 55 Lake Ave North. Worcester Massachusetts United States 01655
9 Holy Medical Center Teaneck New Jersey United States 07666
10 Northwell Health Comprehensive Wound Healing Center Lake Success New York United States 11042
11 Mount Sinai St. Luke's hospital New York New York United States 10019-1147
12 Duke University Medical Center,Durham,2424 Erwin Road Hock Plaza Durham North Carolina United States 27710
13 Austin Heart Clinical Research Austin Texas United States 78756
14 Department of Plastic Surgery ,Ut Southwestern Medical Center Dallas Texas United States 75390-9132
15 UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery Burgas Bulgaria 8127
16 MHAT Sveti Nokolay Chudotvorets EOOD - Lom,Surgery Department,Address 2, Todor Kableshkov str. Lom Bulgaria 3600
17 UMHAT "St. Georgi" EAD,Clinic: Vascular Surgery and Angiology 66 "Peshtersko Shosse" Blvd., 8th floor, Hirurgicheski blok Plovdiv Bulgaria 4001
18 UMBAL Kanev AD - Ruse,Department of Vascular Surgery Address: 2, Nezavisimost str Ruse Bulgaria 7002
19 UMHAT "Medica" Ruse Department of Vascular Surgery 35, "Riga", Str Post code: 7013 Ruse, Bulgaria Ruse Bulgaria 7013
20 MHAT National Heart Hospital EAD,Clinic of Vascular Surgery and angiology Sofia Bulgaria 1309
21 Acibadem City Clinic MHAT Tokuda, Vascular Surgery and Angiology 51B "Nikola Vaptzarov" Blvd Sofia Bulgaria 1407
22 UMHAT "St. Ekaterina" EAD, Departement of Vascular Surgery Sofia Bulgaria 1431
23 Cevni ambulance Hodonín Czechia 69501
24 Angiologicka ambulance Ostrava Dubina Czechia 700 30
25 Vseobecna Fakultni Nemocnice v Praze Prague Czechia 12802
26 Intitute of Clinical and Experimental Medicine Praha 4 Czechia 140 21
27 Krajska zdravotni a.s., Masarykova nemocnice o.z. Usti nad Labem Czechia 40113
28 Klinik und Poliklinik für Angiologie Universitätsklinikum Leipzig AöR Liebigstr. 20 04103 Leipzig, Germany Leipzig Saxony Germany 04103
29 Medinos Klinikum Sonneberg Abteilung für Kardiologie/Angiologie - Studienambulanz Neustadter Straße 61 96515 Sonneberg Germany Sonneberg Thueringen Germany 96515
30 Universitats-Herzzentrum Freiburg Bad Krozingen Germany 79189
31 Charite Centrum fur Herz - Kreislauf - und Gefassmedizin - Campus Benjamin Franklin Berlin Germany 12203
32 HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie Berlin Germany 13125
33 Universitätsklinikum Carl Gustav Carus Dresden Germany
34 Heinrich-Heine-Universitaet Duesseldorf - Universitaetsklinikum Duesseldorf (UKD) Duesseldorf Germany 40225
35 Asklepios Klinik St.Georg-Angiologische Ambulanz Hamburg Germany 20099
36 Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany Kösching Germany 85092
37 Universitaetsklinikum Muenster Muenster Germany 48155
38 Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz Szekesfehervar Fejer Hungary 8000
39 Szent Imre Egyetemi Oktato Korhaz Budapest Hungary 1115
40 Flor Ferenc County Hospital Kistarcsa Hungary 2143
41 B-A-Z County and University Teaching Hospital Miskolc Hungary 3526
42 Josa Andras Megyei Korhaz Nyíregyháza Hungary 4400
43 Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School) Pecs Hungary 7624
44 Barzilai Medical Center Ashkelon Israel 78100
45 Blood Vessel Day Care at Clalit Community Horev Center, Horev Center Haifa Israel 3434119
46 Vascular Surgery Department, Hadassah Ein Karem MC Jerusalem Israel 91120
47 Vascular Surgery Department Rabin Medical Center Beilinson Hospital, 39 Jabotinski St. Petah Tikva Israel 4941492 Petah Tikva Israel 4941492
48 The Cardiological Department, The Baruch Padeh Medical Center Poriyya 'Illit Israel 15208
49 Acibadem Sistina Hospital,Thoracic and Vascular Surgery Skopje North Macedonia 1000
50 Re-Medika General Hospital,Cardiovascular Surgery Skopje North Macedonia 1000
51 Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery Skopje North Macedonia 1000
52 Cathedra and Clinic of Vascular Surgery and Angiology-Klinika Chirurgii Naczyniowej i Angiologii Lublin Poland 20-081
53 Wojewodzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo-Rozwojowy,Intensywnego Nadzoru Kardlologleznego, Wrocław Poland 51-124
54 Vascular Research Clinical Research Centre Beaufort Way Southmead Hospital Westbury on Trym Bristol Bristol United Kingdom BS10 5NB
55 Hull And East Yorkshire Women And Children's Hospital-Hull And East Yorkshire Hospitals Nhs Trust Hull United Kingdom HU32JZ
56 Kings College Hospital London United Kingdom SE5 9RS
57 Department of Vascular Research, St George's Hospital London United Kingdom SW17 0QT

Sponsors and Collaborators

  • Pluristem Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Pluristem Ltd.
ClinicalTrials.gov Identifier:
NCT03006770
Other Study ID Numbers:
  • PLX-CLI-03
First Posted:
Dec 30, 2016
Last Update Posted:
Dec 28, 2020
Last Verified:
Dec 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Ischemia

Study Results

No Results Posted as of Dec 28, 2020