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

NCT03006770 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: PLX-CLI-03
• Study Type: interventional
• Target: 213
• Locations: 9 countries
• Sites: 57

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.

Conditions

Critical Limb Ischemia (CLI)

Outcome Measures

Primary Outcomes (1)

• Time to major amputation or death (AFS)

  Up to 36 months from enrollment

Secondary Outcomes (5)

• 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

• 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

Study Arms (2)

PLX-PAD

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

PLX-PAD BIOLOGICAL

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

PLX-PAD

Placebo BIOLOGICAL

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

Placebo

Eligibility Criteria

• Age: 45 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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 .

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pluristem Ltd.: lead

Study Sites (57)

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

Irvine, California, 92697, United States

Location

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

Los Angeles, California, 90211, United States

Location

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

Sacramento, California, 95817, United States

Location

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

Sacramento, California, 95817, United States

Location

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

Miami, Florida, 33136-1015, United States

Location

Miami Cardiac and Vascular Institute Baptist Health South Florida

Miami, Florida, 33176, United States

Location

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

Boston, Massachusetts, 02111-1552, United States

Location

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

Worcester, Massachusetts, 01655, United States

Location

Holy Medical Center

Teaneck, New Jersey, 07666, United States

Location

Northwell Health Comprehensive Wound Healing Center

Lake Success, New York, 11042, United States

Location

Mount Sinai St. Luke's hospital

New York, New York, 10019-1147, United States

Location

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

Durham, North Carolina, 27710, United States

Location

Austin Heart Clinical Research

Austin, Texas, 78756, United States

Location

Department of Plastic Surgery ,Ut Southwestern Medical Center

Dallas, Texas, 75390-9132, United States

Location

UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery

Burgas, 8127, Bulgaria

Location

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

Lom, 3600, Bulgaria

Location

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

Plovdiv, 4001, Bulgaria

Location

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

Rousse, 7002, Bulgaria

Location

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

Rousse, 7013, Bulgaria

Location

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

Sofia, 1309, Bulgaria

Location

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

Sofia, 1407, Bulgaria

Location

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

Sofia, 1431, Bulgaria

Location

Cevni ambulance

Hodonín, 69501, Czechia

Location

Angiologicka ambulance

Ostrava Dubina, 700 30, Czechia

Location

Vseobecna Fakultni Nemocnice v Praze

Prague, 12802, Czechia

Location

Intitute of Clinical and Experimental Medicine

Prague, 140 21, Czechia

Location

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

Ústí nad Labem, 40113, Czechia

Location

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

Leipzig, Saxony, 04103, Germany

Location

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

Sonneberg, Thuringia, 96515, Germany

Location

Universitats-Herzzentrum Freiburg

Bad Krozingen, 79189, Germany

Location

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

Berlin, 12203, Germany

Location

HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie

Berlin, 13125, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Location

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

Düsseldorf, 40225, Germany

Location

Asklepios Klinik St.Georg-Angiologische Ambulanz

Hamburg, 20099, Germany

Location

Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany

Kösching, 85092, Germany

Location

Universitaetsklinikum Muenster

Münster, 48155, Germany

Location

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

Székesfehérvár, Fejér, 8000, Hungary

Location

Szent Imre Egyetemi Oktato Korhaz

Budapest, 1115, Hungary

Location

Flor Ferenc County Hospital

Kistarcsa, 2143, Hungary

Location

B-A-Z County and University Teaching Hospital

Miskolc, 3526, Hungary

Location

Josa Andras Megyei Korhaz

Nyíregyháza, 4400, Hungary

Location

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

Pécs, 7624, Hungary

Location

Barzilai Medical Center

Ashkelon, 78100, Israel

Location

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

Haifa, 3434119, Israel

Location

Vascular Surgery Department, Hadassah Ein Karem MC

Jerusalem, 91120, Israel

Location

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

Petah Tikva, 4941492, Israel

Location

The Cardiological Department, The Baruch Padeh Medical Center

Poria Illit, 15208, Israel

Location

Acibadem Sistina Hospital,Thoracic and Vascular Surgery

Skopje, 1000, North Macedonia

Location

Re-Medika General Hospital,Cardiovascular Surgery

Skopje, 1000, North Macedonia

Location

Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery

Skopje, 1000, North Macedonia

Location

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

Lublin, 20-081, Poland

Location

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

Wroclaw, 51-124, Poland

Location

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

Bristol, BS10 5NB, United Kingdom

Location

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

Hull, HU32JZ, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Department of Vascular Research, St George's Hospital

London, SW17 0QT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 38294084 DERIVED

• 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.

  PMID: 30686676 DERIVED

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2016
• First Posted: December 30, 2016
• Study Start: May 22, 2017
• Primary Completion: March 3, 2021
• Study Completion: April 20, 2022
• Last Updated: August 30, 2024

Record last verified: 2024-08

Locations

US (14); BU (8); DE (10); GB (4); PL (2); HU (6); IL (5); CZ (5); NO (3)