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Critical Limb Ischemia (CLI)Phase 3NCT03006770

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

A Phase 3 study testing PLX-PAD in people with Critical Limb Ischemia (CLI), run by Pluristem Ltd. at 57 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 45 to 99 years
Conditions the study is for
Critical Limb Ischemia (CLI)
What is being tested?
PLX-PAD
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
213 participants
Where
57 sitesin 9 countries
Study dates
22 May 2017to 20 Apr 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • 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)
  • 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).
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  • 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 .

Who cannot join

  • 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.
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  • 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.
  • 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.
  • Use of hyperbaric oxygen therapy, prostanoids, spinal cord stimulation, lumbar sympathectomy, wound dressing containing cells or growth factors, or topical platelet derived growth factor.
  • Known allergies to any of the following: DMSO, human serum albumin, bovine serum albumin.
  • History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with IV steroids/epinephrine.
  • Pulmonary disease requiring supplemental oxygen treatment on a daily basis.
  • Active malignancy or history of malignancy within 5 years prior to study entry.
  • In the opinion of the investigator, the subject is unsuitable for participating in the study.
  • Chronic liver disease Child Pugh class B\C

Trial locations and contacts

57 sites in 9 countries.

57 sites in 9 countries

United States14 sites

  • Austin Heart Clinical Research

    Austin, Texas, 78756

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

    Boston, Massachusetts, 02111-1552

  • Department of Plastic Surgery ,Ut Southwestern Medical Center

    Dallas, Texas, 75390-9132

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

    Durham, North Carolina, 27710

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

    Irvine, California, 92697

  • Northwell Health Comprehensive Wound Healing Center

    Lake Success, New York, 11042

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

    Los Angeles, California, 90211

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

    Miami, Florida, 33136-1015

  • Miami Cardiac and Vascular Institute Baptist Health South Florida

    Miami, Florida, 33176

  • Mount Sinai St. Luke's hospital

    New York, New York, 10019-1147

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

    Sacramento, California, 95817

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

    Sacramento, California, 95817

  • Holy Medical Center

    Teaneck, New Jersey, 07666

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

    Worcester, Massachusetts, 01655

Other trials in United States

Germany10 sites

  • Universitats-Herzzentrum Freiburg

    Bad Krozingen, 79189

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

    Berlin, 12203

  • HELIOS Klinikum Berlin-Buch, Klinik fur Angiologie

    Berlin, 13125

  • Universitätsklinikum Carl Gustav Carus

    Dresden

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

    Düsseldorf, 40225

  • Asklepios Klinik St.Georg-Angiologische Ambulanz

    Hamburg, 20099

  • Klinik Kösching Krankenhausstr. 19, 85092 Kösching Germany

    Kösching, 85092

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

    Leipzig, Saxony, 04103

  • Universitaetsklinikum Muenster

    Münster, 48155

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

    Sonneberg, Thuringia, 96515

Other trials in Germany

Bulgaria8 sites

  • UMHAT "Virgin Mary" EOOD,Clinic of Vascular Surgery

    Burgas, 8127

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

    Lom, 3600

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

    Plovdiv, 4001

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

    Rousse, 7002

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

    Rousse, 7013

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

    Sofia, 1309

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

    Sofia, 1407

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

    Sofia, 1431

Other trials in Bulgaria

Hungary6 sites

  • Szent Imre Egyetemi Oktato Korhaz

    Budapest, 1115

  • Flor Ferenc County Hospital

    Kistarcsa, 2143

  • B-A-Z County and University Teaching Hospital

    Miskolc, 3526

  • Josa Andras Megyei Korhaz

    Nyíregyháza, 4400

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

    Pécs, 7624

  • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

    Székesfehérvár, Fejér, 8000

Other trials in Hungary

Czechia5 sites

  • Cevni ambulance

    Hodonín, 69501

  • Angiologicka ambulance

    Ostrava Dubina, 700 30

  • Vseobecna Fakultni Nemocnice v Praze

    Prague, 12802

  • Intitute of Clinical and Experimental Medicine

    Prague, 140 21

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

    Ústí nad Labem, 40113

Other trials in Czechia

Israel5 sites

  • Barzilai Medical Center

    Ashkelon, 78100

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

    Haifa, 3434119

  • Vascular Surgery Department, Hadassah Ein Karem MC

    Jerusalem, 91120

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

    Petah Tikva, 4941492

  • The Cardiological Department, The Baruch Padeh Medical Center

    Poria Illit, 15208

Other trials in Israel

United Kingdom4 sites

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

    Bristol, BS10 5NB

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

    Hull, HU32JZ

  • Kings College Hospital

    London, SE5 9RS

  • Department of Vascular Research, St George's Hospital

    London, SW17 0QT

Other trials in United Kingdom

North Macedonia3 sites

  • Acibadem Sistina Hospital,Thoracic and Vascular Surgery

    Skopje, 1000

  • Re-Medika General Hospital,Cardiovascular Surgery

    Skopje, 1000

  • Special Hospital for Surgical Diseases Zan Mitrev Clinic ,Cardiovascular Surgery

    Skopje, 1000

Other trials in North Macedonia

Poland2 sites

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

    Lublin, 20-081

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

    Wroclaw, 51-124

Other trials in Poland

About this study

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.

Being tested
PLX-PAD, Placebo
Medical subject headings
Chronic Limb-Threatening Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PLX-PADBiological

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

  • PlaceboBiological

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

Study groups in NCT03006770
Study groupRoleWhat they receive
PLX-PADExperimentalPLX-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.
Receives: Biological: PLX-PAD
PlaceboPlacebo comparatorPlacebo 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.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to major amputation or death (AFS)

    Measured: Up to 36 months from enrollment

Secondary outcomes (5)

  1. Time to first occurrence of any of the events (in index leg)-major amputation, revascularization due to worsening of CLI, All-cause mortality.

    Measured: Up to 36 months from enrollment

  2. Time to major amputation of the index leg.

    Measured: Up to 36 months from enrollment

  3. 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".

    Measured: 6 months from enrollment

  4. Proportion of subjects with complete healing of all ischemic lesions i.e., ulcers and necroses in the index leg at 12 months.

    Measured: 12 months from enrollment

  5. Time (days) from randomization to occurrence of death.

    Measured: Up to 36 months from enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2016 (estimated)
  2. Study start22 May 2017
  3. Primary completion3 Mar 2021
  4. Study completion20 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
213 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03006770
Sponsor's protocol ID
PLX-CLI-03
Status last verified
Aug 2024
First submitted
27 Dec 2016
Last updated
30 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38294084

  • 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.

    PubMed 30686676

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PLX-PAD in people with Critical Limb Ischemia (CLI), run by Pluristem Ltd. at 57 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in United States, Germany, Bulgaria, Hungary, Czechia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to major amputation or death (AFS) (time frame: Up to 36 months from enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03006770, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2024.

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