study of the safety of therapeutic tx with immunomodulatory msc in adults with covid-19 infection requiring mechanical ventilation

Conditions: COVID

Summary: this is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with coronavirus disease 2019 (covid-19). this clinical trial will evaluate the preliminary safety and efficacy of bm-allo.msc vs placebo in treating subjects with severe disease requiring ventilator support during covid 19 infection.


Eligibility criteria:
inclusion criteria: 1. age ≥ 18 years old. 2. able to understand and provide a signed informed consent that fulfills the relevant institutional review board (irb) or independent ethics committee (iec) guidelines. for subjects that are intubated and/or sedated, or otherwise unable to provide consent, prospective consent from a legally-authorized representative is required. the subject or his/her legally authorized representative must be able to provide consent. 3. has laboratory-confirmed positive novel coronavirus (sars-cov-2) test, as determined by polymerase chain reaction (pcr), or other commercial or public health assay in any specimen \< 72 hours prior to enrollment, or meets the criteria to guide the evaluation and testing of patients under investigation (pui) for covid-19 (https://emergency.cdc.gov/han/2020/han00428.asp). 4. requiring mechanical ventilatory support with moderate to severe acute respiratory distress syndrome (ards) as determined by the berlin criteria: 1. bilateral opacities present on a chest radiograph or computed tomographic (ct) scan. these opacities are not fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules. 2. origin of edema: respiratory failure not fully explained by cardiac failure or fluid overload. 3. oxygenation: moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (pao2/fio2). the severity of the hypoxemia defines the severity of the ards: * moderate: pao2/fio2 \>100 mmhg and ≤ 200 mmhg, on ventilator settings that include peep ≥ 5 cm h2o * severe: pao2/fio2 ≤100 mmhg on ventilator settings that include peep ≥5 cm h2o subjects receiving extracorporeal membrane oxygenation (ecmo) will not be enrolled in this study. 5. high-sensitivity c-reactive protein (hs-crp) serum level \> 4.0 mg/dl 6. acute physiology and chronic health evaluation (apache iv) score \> 5 7. agrees to the collection of nasopharyngeal (np) swabs and venous blood per protocol. 8. ability to attend required study visits and return for adequate follow-up, as required by this protocol. 9. agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. female subjects of child-bearing potential must agree to use effective contraception while on study and for at least 1 month after the last dose of bm-allo.msc. non-sterile male subjects must agree to use a condom while on study and for up to 1 month after the dose of bm-allo.msc. effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (iuds), oral contraceptives, and abstinence. exclusion criteria: 1. known hypersensitivity to any component of the study medication(s). 2. signs of multisystem organ failure. liver function tests (lfts) \> 5x normal. 3. intubated \> 72 continuous hours. 4. assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol. 5. pregnant and nursing women. a negative serum pregnancy test during screening (within 72 hours prior to the first dose) must be documented before mscs are administered to a female subject of child-bearing potential.

Keywords: immunomodulatory mesenchymal stem cells msc covid-19 mechanical ventilation severe respiratory distress