Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Lomecel-B (RECOVER)

A Phase I, double- blinded, randomized, placebo- controlled study to test the safety of Lomecel-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 from influenza 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).

Eligibility Criteria:
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.