A placebo-Controlled,Phase III Study to Evaluate the Efficacy, Tolerability and Safety of Intramuscular Injections of PLX-PAD for the Treatment of Patients with Critical Limb Ischemia (CLI) with Minor Tissue Loss who are Unsuitable for Revascularizatio

Phase 1

• Conditions: Critical Limb Ischemia (CLI); MedDRA version: 21.1Level: LLTClassification code 10058069Term: Critical limb ischemiaSystem Organ Class: 100000004866; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-005532-18-DE
• Lead Sponsor: Pluristem Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-06-27
• Last Update Posted: 12 April 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Adult male or female subjects between ages 45-99 years of age at the
time of screening.
2. Subjects with a diagnosis of PAD due to atherosclerosis at the stage of
CLI, with minor tissue loss from arterial disease, up to the ankle level
(the line between the top of the two malleoli) (black toe due to CLI is
acceptable if not infected).
3. Total area of ischemic lesions =20cm2 (not including black toes).
4. Total area of ischemic lesions in the heel =10cm2.
5. AP =70 mmHg or TP =50 mmHg in the index leg. If a subject has both
ABI >1.4 or both AP and TP are not measureable or not reliable,
inclusion may be based on TcPO2 =30 mmHg.
6. Subject unsuitable for revascularization (by any method) in the index
leg based on unfavorable risk-benefit assessment of a multidisciplinary
team including a vascular surgeon, and an interventionist/endovascular
specialist (who might be a vascular surgeon,
angiologist/cardiologist/internist, interventional radiologist), and, if
relevant, an anesthesiologist, confirmed once during Screening Period.
Unsuitability to revascularization is based any of the following:
? Anatomic considerations as: inappropriate target artery,
diffuse/extensive tibial and/or peroneal artery lesions, inadequate distal
run-off
? Technical considerations as: inappropriate bypass conduit
?Failed revascularization (with persistence of CLI as defined in this
protocol)
? Medical considerations: subject's comorbidities.
7. Ischemic lesions in the index leg must not have closed during the
Screening Period, nor significantly worsened.
8. Ischemic ulcers in the index leg without tendon or bone exposure
during Screening Period, unless the exposure is secondary to a minor
amputation and there are no signs of osteomyelitis as per clinical
assessment and imaging.
9. Under treatment for cardiovascular risk factors: hypertension,
hyperlipidemia, diabetes, in accordance with applicable guidelines, in
order to achieve their stabilization. Concomitant therapy should include
a statin (or other lipid lowering drugs as part of standard of care) and an
anti-platelet agent (e.g., clopidogrel, aspirin, etc.) for at least 2 weeks
prior to randomization as part of standard of care (unless
contraindicated or unless subject is under chronic oral anticoagulation).
Subject has received recommendations on lifestyle changes (including
smoking cessation) prior to randomization.
10. 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:
a. Oral/intravaginal/transdermal combined estrogen and progestogen
containing hormonal contraception for at least 3 months prior to
screening
b. Oral/injectable/implantable progestogen-only hormonal
contraception for at least 3 months prior to screening
c. An intrauterine device (IUD) or intrauterine hormone-releasing
system (IUS)
Any female subject who is surgically sterile, or with bilateral tubal
occlusion, or whose partner is vasectomized, or who reliably applies
sexual abstinence or who is postmenopausal (2 years without menses)
will be considered not of childbearing potential.
11. Subject understood, agreed and provided informed consent. Patients
must give written informed consent before any assessment is performed.
12. For Diabetic patients: under treatment with glucose lowering agents
according to acceptable international guidelines.
Are the trial subjects under 18? no
Number of subjects for th

Exclusion Criteria

1. Non-atherosclerotic PAD
2. CLI with major tissue loss (Rutherford Category 6) in either leg.
3. Evidence of active infection in either leg (e.g., cellulitis,
osteomyelitis).
4. Subject having undergone surgical revascularization or major
amputation, in either leg, less than 1mth prior to screening, or
endovascular revascularization or minor amputation less than 2wks prior
to screening
5. Planned or potential need for major/minor amputation or any
revascularization of either leg during the Screening Period and up to
1mth following randomization according to Investigator's or treating
physician judgment/decision.
6. Aortoiliac stenosis or common femoral artery stenosis =70%, or
otherwise suspicion of inadequate inflow to the index leg up to 3 months
prior to screening by any imaging modality.
7. Current evidence or sign supporting an assessment of life expectancy
of less than 6mths
8. Stroke or acute myocardial infarction/unstable angina within 3mths
prior to randomization
9. Severe congestive heart failure symptoms (New York Heart
Association class III- IV) at screening
10. Life-threatening ventricular arrhythmia except in subjects with an
implantable cardiac-defibrillator at screening
11. Uncontrolled severe hypertension during screening period
12. Diabetes mellitus with HbA1c >10% at screening
13. Current or history of proliferative retinopathy (for all known diabetic
subjects there will be no evidence of proliferative retinopathy in a retinal
examination performed within 3mths before First Screening Visit or
during screening)
14. Known active untreated Hepatitis B virus or Hepatitis C virus
infections at screening
15. A subject with known human immunodeficiency virus infection,
acquired immunodeficiency syndrome, severe uncontrolled inflammatory
disease or severe uncontrolled autoimmune disease
16. Pre-existing significant coagulopathies that put the subject at an
increased risk of blood clotting or bleeding according to the
Investigator's judgment
17. Subjects under chronic anticoagulant therapy taking warfarin with
international normalized ratio (INR)>2 or treated with Direct Oral
Anticoagulants, for atrial fibrillation and\or prosthetic heart valves, and
or thromboembolic events, unless this therapy can be safely
discontinued or modified around the time of PLX-PAD/placebo injections
based on the study Investigator's discretion.
18. Aspartate transaminase or alanine transaminase >3×ULN. Subjects
with higher levels may be included if the condition associated with the
increase in those liver enzymes is known and considered clinically stable
19. Subject on renal replacement therapy or planned to start renal
replacement therapy within 3 months of first screening visit.
20. Known history of drug or alcohol abuse in the past 3yrs
21. Subject is currently enrolled in, or has not yet completed a period of
at least 30days since ending another investigational device or drug
trial(s), unless in long-term follow-up phase (in which there is no IP
administration)
22. Current treatment with systemic steroids at a dose which is
prednisone equivalent >5mg/day, or topical steroids on the index leg
23. Current use or use within 30days prior to PLX-PAD treatment of
wound dressing containing cells or growth factors like Apligraf®, or
topical platelet derived growth factor
24. Planned use, or use within 14days prior to PLX-PAD treatment (VI)
of hyperbaric oxygen therapy, prostanoids, Pentoxifylline, Cylostazole,
spinal cord stimulation, or lumbar sym

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified