萝莉社

A study in adults with moderate to severe ARDS consequent to sepsis, septic shock, trauma, and/or bacterial or viral pneumonia, who have been hospitalized. The safety and tolerability, PK, preliminary efficacy, and pharmacodynamic of a single IV infusion of ALT-100 will be assessed. Patients with respiratory distress admitted to the hospital will be screened for study eligibility. Participants included in the study can be patients requiring immediate intubation/mechanical ventilation, as well as patients receiving heated and humidified HFNO (鈮� 30 L/min) or non-invasive ventilation, provided oxygenation criteria for moderate or severe ARDS are met. All participants will receive study drug within 12 hours of their moderate or severe ARDS diagnosis or from when oxygenation criteria for moderate or severe ARDS are met, as applicable, and within 6 hours of initiation of ventilation. 聽

Inclusion

Hospitalized (or documentation of a plan to admit to the hospital if the patient is in an emergency department) male or non-pregnant female 鈮� 18 years of age at time of enrollment. Participant (or LAR) is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form.

Participant has a diagnosis of moderate or severe Ards according to the Berlin definition of Ards:

a) Acute onset of respiratory distress failure< 1 week of a known clinical insult or new/worsening respiratory symptoms b) Respiratory distress failure associated with known ARDS risk factors and not fully explained by either cardiac failure or fluid overload (an objective assessment of cardiac failure or fluid overload is needed if no risk factors for ARDS are present) c) Radiological abnormalities on chest x-ray or computed tomography (CT) scan, ie, bilateral opacities that are not fully explained by effusions, nodules, masses, or lobar/lung collapse. d) Hypoxemia: PaO2/FiO2 > 400 mmHg, HFNO gas flow of 鈮� 20 L/min, NIPPV (BiPAP/CPAP) for hypoxemia

i. Moderate ARDS: PaO2/FiO2 > 100 mmHg (> 13.3 kPa) to 鈮� 200 mmHg (鈮� 26.6 kPa) with PEEP 鈮� 5 cmH2O, or imputed SpO2/FiO2 equivalent. ii. Severe ARDS: PaO2/FiO2 鈮� 100 mmHg (鈮� 13.3 kPa) with PEEP 鈮� 5 cmH2O Exclusion Participants with ARDS consequent to COVID-19 infection. Participants requiring immediate MV who have been intubated and on MV for > 4 hours prior to the planned administration of study treatment on Day 1 Moribund participant not expected to survive > 24 hours, in the opinion of the Investigator. Use of extracorporeal life support (eg, ECMO) or, in the opinion of the Investigator, there is a high likelihood that extracorporeal life support will be initiated within 48 hours after randomization. Participant has an underlying clinical condition where, in the opinion of the Investigator, it would be unlikely that the participant would be able to come off ventilation, eg, chronic progressive neuromuscular or respiratory disease. Severe chronic respiratory disease (eg, known chronic obstructive pulmonary disease [COPD], pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF], interstitial lung disease [ILD]) requiring supplemental oxygen therapy or MV prehospitalization (eg, prior to ARDS diagnosis). Evidence of life-threatening dysrhythmia (eg, ventricular tachycardia, ventricular fibrillation) or cardiac arrest on presentation. Evidence of new or preexisting decompensated heart failure. Absolute neutrophil count < 1000 per mm3. Platelet count < 50,000 per mm3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 脳Upper Limit of Normal (ULN). Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 (based on MDRD equation) or requiring hemofiltration or dialysis.聽

Note: Acceptable imaging tests (chest x-ray, Ct scans) done within 3 days of Day 1 can be used to determine eligibility, however, the radiological and hypoxemia criteria (3 [c] and [d]) must occur within the same 24-hour period. The time of onset of Ards is defined as the time when the last of these 2 Ards criteria is met