A Phase I, double- blinded, randomized, placebo- controlled study to test the safety ofLomecel-B in Adults suffering from mild to severe acute respiratory distress syndrome(ARDS) due to COVID-19 resultant from 2019-nCoV coronavirus infection, or resultant frominfluenza virus infection.
Double-blinded, randomized, placebo-controlled study with 2 cohorts.
Cohort 1: Subjects with ARDS and acutely infected with SARS-CoV-2. Arm 1: 25 subjects
treated with up to 3 doses of 100 million Lomecel-B Arm 2: 10 subjects treated with up to
3 doses of Placebo.
Cohort 2: Subjects with ARDS and acutely infected with influenza virus. Arm 3: 25
subjects treated with up to 3 doses of 100 million Lomecel-B Arm 4: 10 subjects treated
with up to 3 doses of Placebo.
Each subject will be intravenously infused with 100 million Lomecel-B (formerly LMSCs) or
placebo on Day 0. If no treatment-related AEs are seen after the infusion, a second
infusion will be given on Day 3. If no treatment-related AEs are seen after the second
infusion, a third infusion will be given Day 6.
Follow-up visits will be conducted: daily until hospital discharge; at Week 4 after
treatment (with LMSCs or placebo) for patients already discharged; and at Month 6 after
treatment (with LMSCs or placebo).
Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
Longeveron Mesenchymal Stem Cells (LMSCs)
Other: Placebo
Placebo
Inclusion Criteria:
1. Male or female or any race or ethnicity.
2. At least 18 years of age.
3. Provide written informed consent. For subjects who are incapable of providing
informed consent, written informed consent can be provided on behalf of the subject
by a legally authorized representative (LAR).
4. Diagnosis of mild to severe ARDS per the Berlin Definition of ARDS. More
specifically, the following 3 conditions must be present.
1. A need for positive pressure ventilation by an endotracheal or tracheal tube
with a PaO2/FiO2 ratio < 200 with at least 8 cm H2O positive end-expiratory
airway pressure (PEEP). A patient may be included if the PaO2/FiO2 ratio < 200
with < 8 cm H2O PEEP if there is a contraindication to increased PEEP (evidence
of barotrauma).
2. Bilateral infiltrates consistent with pulmonary edema on frontal chest
radiograph.
3. No clinical evidence of left atrial hypertension for bilateral pulmonary
infiltrates.
5. Confirmed diagnosis of infection with coronavirus or influenza virus.
6. Willing to perform all assessments required for the study.
7. Must agree to the collection of all blood samples per protocol.
8. Must agree to have samples stored and used for secondary research.
Exclusion Criteria:
1. Patient receiving Extracorporeal Membrane Oxygenation (ECMO).
2. History of malignancy within previous 2.5 years, except for curatively-treated basal
cell carcinoma, squamous cell carcinoma, melanoma in situ, or cervical carcinoma.
3. Prior positive test for any of the following without demonstration of resolution.
i. Hepatitis B virus (HBV) surface antigen (HBsAg). ii. Viremic hepatitis C virus
(HCV). iii. Human immunodeficiency virus-1 or -2 (HIV1 or 2 HIV2). iv. Human T-cell
leukemia virus-I or -II (HTLV-I or HTLV-II). v. Syphilis.
4. Female who is pregnant, nursing, or of childbearing potential while not practicing
effective contraception.
5. Known hypersensitivity to dimethyl sulfoxide (DMSO).
6. Be an organ transplant recipient, other than for corneal, bone, skin, ligament, or
tendon transplant.
7. Actively listing (or expected listing) for transplant of any organ, other than for
corneal, bone, skin, ligament, or tendon transplant.
8. Continuous use of any medication at immunosuppressive dosing for greater than 14
consecutive days over the past 3 months.
9. Currently participating in an investigational therapeutic or device trial, or have
participated in an investigational therapeutic or device trial within the previous
30 days, or participate in any other clinical trial for the duration of the time
that the subject actively participates in this trial. However, use of
hydroxychloroquine, remdesivir, lopinavir/ritonavir and ivermectin are allowed as
well as convalescent plasma.. Exceptions for other experimental interventions
related to treating the patient's acute illness may be made with prior approval of
Longeveron.
10. Any serious comorbid illness or any other condition that, in the opinion of the
Investigator, may compromise the safety or compliance of the patient or preclude
successful completion of the study, or that may compromise the validity of the
study.
Miami VA Healthcare System
Miami, Florida, United States
University of Maryland Medical Center
Baltimore, Maryland, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States