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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

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ClinicalTrials.gov Identifier: NCT03006770
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Pluristem Ltd.

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
Critical Limb Ischemia (CLI) Biological: PLX-PAD Biological: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 246 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
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

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.




Primary Outcome Measures :
  1. Time to major amputation or death (AFS) [ Time Frame: 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,doubling of total wound area from baseline,anew gangrene. All-cause mortality. [ Time Frame: Up to 36 months from enrollment ]
  2. Time to major amputation of the index leg. [ Time Frame: Up to 36 months from enrollment ]
  3. Complete wound healing in the index leg [ Time Frame: 12 months from enrollment ]
  4. Ischemic pain (NRS). [ Time Frame: 6 months from enrollment ]
  5. Time to adjudicated major amputation of the index leg or death [ Time Frame: Up to 36 months from enrollment ]


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Ages Eligible for Study:   45 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Signed informed consent form.

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] Stage 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) >2.5.
  15. Subject on renal replacement therapy or with eGFR <15 mL/min/1.73m2.
  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. Inability to understand and provide an informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03006770


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Sponsors and Collaborators
Pluristem Ltd.

Responsible Party: Pluristem Ltd.
ClinicalTrials.gov Identifier: NCT03006770     History of Changes
Other Study ID Numbers: PLX-CLI-03
First Posted: December 30, 2016    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Ischemia
Pathologic Processes