JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS (Master Record)

Inclusion Criteria Each participant must meet all of the following criteria to be enrolled in this study: * Participant (or their Legally Authorized Representative (LAR)) provides informed consent and agrees to comply with protocol requirements * Participant is at least 18 years of age or older at the time of consent. * Participant with signs and symptoms of ARDS according to the Berlin definition of ARDS. Note that participants on noninvasive ventilation may be screened. * Participant of childbearing potential must agree to either abstinence or use at least one primary form of contraception, not including hormonal contraception, from the time of screening through Day 28. Additional cohort-specific requirements may apply * Participant agrees to not participate in another investigational interventional study while participating in this study (i.e., through Day 90). Exclusion Criteria Participants will be excluded from the study if any of the following apply: * Participant with ARDS or at risk of developing ARDS due to the following reasons: trauma, large volume aspiration, or transfusion. * Participant with pulmonary edema due to cardiogenic pulmonary edema/fluid overload or hypoxemia primarily attributable atelectasis, in the absence of a predisposing risk factor for ARDS. * Participant who demonstrates an improvement in oxygenation and ventilatory support 24 hours prior to or during screening up to randomization, such that per investigator clinical judgement, the participant is expected to have significant improvement in lung function over subsequent 24 hours regardless of additional interventions. * Participant is known to be pregnant, nursing, or with a positive (urine and/or serum test) pregnancy test. * Participant is anticipated to be transferred to another hospital which is not a study site within 72 hours. * Participant is not expected to survive for 72 hours. * Participant has been on invasive mechanical ventilation or ECMO for ARDS for more than 48 hours for ARDS at the time of consent. * Participant has an underlying clinical condition where, in the opinion of the Investigator and based on their clinical judgement, it would be extremely unlikely that the participant would come off ventilation * Participant has severe COPD requiring continuous long-term home oxygen therapy or mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP or bi-level positive airway pressure used solely for sleep-disordered breathing. * Participant has interstitial lung disease or idiopathic pulmonary fibrosis requiring continuous chronic home oxygen therapy. * Participant has NY Heart Association Class IV congestive heart failure. * Participant has a known allergy to any study medication or any of its excipients. * Participant is receiving systemic immunosuppressive therapy for solid organ or hematopoietic cancer or transplant anti-rejection medication therapy OR systemic immunosuppressive corticosteroids (prednisone ≥20 mg daily or equivalent). NOTE: Patients onreceiving chronic low dose immunosuppressive therapy may be enrolled(e.g., prednisone \<20 mg/day or equivalent) and patients on stable, long-term maintenance immunosuppression (e.g., tacrolimus, mycophenolate, orsirolimus) and patients receiving physiologic replacement and hormonal therapies for breast cancer (e.g., tamoxifen, letrozole) or prostate cancer (leuprolide, bicalutamide) for \>60 days may be eligible at the investigator's discretion of the investigator in consultation with the medical monitor. * Participant is receiving ongoing cytotoxic chemotherapy (IV or oral), OR combination targeted/immunotherapy regimens for cancer within the past 60 days. Note: Participants receiving non-myelosuppressive cancer therapy (e.g., hormonal therapy or selected targeted / immunotherapy regimens) may be eligible if therapy has been stable ≥60 days; The use of hydroxyurea to manage patients with chronic myeloid leukemia, polycythemia vera, essential thrombocythemia or sickle cell disease is permitted. * Participant received treatment with an investigational immunomodulator or immunosuppressant drugs within 5 half-lives or 30 days (whichever is longer) before randomization. * Participant with concurrent infections or history of the following: 1. Known active tuberculosis, 2. Known active Hepatitis B, or 3. HIV and a CD4 count less than 50 or a detectable viral load of \>200 copies/mL HIV RNA. * Participant received treatment with any other investigational drugs within 30 days prior to consent. * Participant had a history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 28 days of screening or inadequate wound healing secondary to major thoracoabdominal surgery at the time of screening. * Participant is considered by the investigator, for any reason, to be an unsuitable candidate for the study. Participant may have additional cohort-specific requirements.