Pneumonia or Acute Respiratory Distress Syndrome (ARDS) caused by severe COVID-19 disease MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: PLX-PAD
Pharmaceutical Form: Dispersion for injection
INN or Proposed INN: emiplacel
Other descriptive name: PLX-PAD
Concentration unit: Munit million units
Concentration type: up to
Con
Sponsors
Pluristem Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the inclusion criteria listed below to be eligible for the study: 1. Willing and able to provide written informed consent, or with a legal representative (as defined by local regulation) who can provide informed consent. 2. Male or non-pregnant female 18 to 85 years of age at time of randomization. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in any specimen within up to 28 days prior to randomization. 4. Meets definition of ARDS according to Berlin criteria with oxygenation of PaO2/FIO2 = 200 mm Hg (graded as Moderate or Severe). 5. By the time of expected treatment initiation on invasive mechanical ventilation for less than 72 hours. 6. Women of childbearing potential must have a negative serum pregnancy test at primary screening and must be willing to use at least one highly effective birth control method throughout the study. 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 (one year without menses) will be considered not of childbearing potential. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Subjects with any one of the exclusion criteria listed below will not be eligible for the study (based on medical record at current admission): 1. Mild ARDS as defined by Berlin criteria (200 mm Hg 15 (mcg/kg/min), vasopressin >0.04 (units/min), phenylephrine >1 (mcg/kg/min), epinephrine =0.3 (mcg/kg/min), or norepinephrine =0.3 (mcg/kg/min). 7. Known allergy to any of the following: dimethyl sulfoxide (DMSO), human serum albumin, bovine serum albumin. 8. Stroke or acute myocardial infarction within 3 months before current hospital admission. 9. Congestive heart failure (New York Heart Association [NYHA] class III-IV) at primary screening (stated in medical history) or investigator discretion as to presence of moderate to severe baseline congestive heart failure. 10. Chronic Obstructive Pulmonary disease GOLD stage above III (Stated in medical history or investigator discretion of severe COPD. 11. Other chronic pulmonary disease under chronic oxygen treatment. 12. Known medical history of Acquired immunodeficiency syndrome (AIDS) or HIV under chronic treatment. 13. Known medical history of Active acute or chronic HBV or HCV (recovered patients are allowed). 14. Known medical history of active tuberculosis or active tuberculosis including under treatment at time of primary screening (not including latent TB). 15. Pre-existing significant coagulopathies that put the patient at an increased risk of major bleeding according to the Investigator’s judgment. 16. History of thromboembolism or known chronic hypercoagulopathic syndrome\state. 17. Subjects under acute or chronic anticoagulant therapy (warfarin with international normalized ratio (INR) >2 or Direct Oral Anticoagulants, or full dose subcutaneous or intravenous treatment for atrial fibrillation and\or prosthetic heart valves, and or suspicion or proven thromboembolic events), unless this therapy is required and can be safely modified, according to local clinical routines (e.g. PTT monitoring, timing of low molecular heparin injections), around the time of PLX-PAD injections based on the study Investigator’s/ treating physician’s discretion and patient’s risk of bleeding. 18. Subject is currently enrolled in another* controlled clinical trial(s) with investigational drug, unless in long-term follow-up phase (in which there is no IP administration). *patients enrolled in another clinical trial in which the investigational product is an anticoagulant may be included in the study. 19. Exposure to allogeneic cell-based therapy in the past or exposure to autologous cell therapy in the last 12 months before screening. 20. History of solid organ transplantation. 21. Active malignancy or history of malignancy within 3 years prior to screening except for successfully resected skin basal cell carcinoma or skin squamous cell carcinoma. 22. Treatment with extracorporeal membrane oxygenation (ECMO) support (at time of randomization). 23. In the opin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of intramuscular (IM) administration of PLX-PAD for the treatment of severe COVID-19;Secondary Objective: Not applicable;Primary end point(s): Number of ventilator free days (time-frame of 28 days from Day 1 through Day 28 of the study, inclusive);Timepoint(s) of evaluation of this end point: day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. All-cause mortality (Time frame 28 and 60 days) 2. Duration of mechanical ventilation (Time frame 28 and 60 days) 3. Mean improvement relative to baseline on a 7-point ordinal scale (Time frame 28 and 60 days): •Not hospitalized, no limitations on activities •Not hospitalized, limitation on activities; •Hospitalized, not requiring supplemental oxygen; •Hospitalized, requiring supplemental oxygen; •Hospitalized, on non-invasive ventilation or high flow oxygen devices; •Hospitalized, on invasive mechanical ventilation or ECMO; •Death. 4. Ordinal outcome assessed daily while hospitalized and on Days 14 and 28 5. ICU-free days (time frame 28 and 60 days) 6. Hospitalization-free days (time frame 60 days) 7. Proportion of subjects with suspected or confirmed Pulmonary Fibrosis (Time frame 52 weeks);Timepoint(s) of evaluation of this end point: 1. days 1,2,3,4,7,14,28,60 2. days 28 and 60 3. days 1,7,14,28,60 4. days 1,2,3,4,7,14,28 5. days 28 and 60 6. days 28 and 60 7. Week 52 | — |
Countries
Bulgaria, Germany, Israel
Contacts
Public ContactClinical Trial Information
Pluristem Ltd.
Outcome results
None listed