Terminated (based on Part A results, Bayer decided to not continue investigating BAY 1097761 further in Part B; this was not due to any safety data for BAY 1097761)

The study is composed of two parts. In part A of the study two active doses of inhaled pegylated adrenomedullin (PEG-ADM) will be compared regarding safety and efficacy to a substance that has no therapeutic effect (placebo) in order to find an optimal and safe of the study drug. In part B of the study the highest dose that is considered safe and has demonstrated efficacy will be taken forward to collect information how well patients suffering from Acute Respiratory Distress Syndrome (ARDS) respond to treatment with inhaled pegylated adrenomedullin (PEG-ADM) compared to treatment with placebo. ARDS is a type of lung failure that cause fluid to build up in the lungs making breathing difficult or impossible.

Inclusion Criteria:

• ≥18 years of age at the time of inclusion into study.

• Invasively mechanically ventilated acute respiratory distress syndrome [ARDS] patients (diagnosed according to Berlin definition of ARDS, including positive end-expiratory pressure [PEEP] of ≥5 cm H2O, X-ray (or CT scan) indicative of ARDS: bilateral opacities not fully explained by cardiac failure, fluid overload, lobar/lung collapse, effusions or nodules).

• Initial diagnosis of mild, moderate or severe ARDS prior to study inclusion, with acute onset of ARDS within 1 week after suspected trigger factor of

  • Pneumonia
  • Aspiration
  • Sepsis
  • Pancreatitis

• Prior to randomization, hypoxemia with PaO2:FiO2 ≤300 mmHg continuously observed for a period of ≥4 hours (with values of ≥2 arterial blood gas [ABG] analyses during that time, with the last value obtained timely (generally ≤3 hours) prior to randomization), under ventilation with minimum PEEP ≥8 cm H2O.

• Time from first meeting the last diagnostic ARDS criterion (Berlin criteria) to randomization must be ≤48 hours.

• For Study Part A: ARDS patients for whom measurements of extra-vascular lung water are regarded as medically indicated by the treating physician, and these measurements are planned as part of their clinical care, from Study Day 1 up to Study Day 7 (if then still intubated).

Exclusion Criteria:

• Any value of a PaO2:FiO2 ratio >300 mmHg within a time interval of 4 hours before randomization
• Rescue therapy (e.g. inhalation of nitric oxide gas and/or inhalation of prostacyclin analogues, or extra corporeal membrane oxygenation [ECMO] / extra corporeal CO2 removal [ECCO2R]) already initiated at screening and/or Study Day 1 (prior to first dose of the study intervention)
• Moribund participants not expected to survive 24 hours (clinical decision)
• Expected duration of invasive mechanical ventilation less than 48 hours (clinical decision)
• History of co-morbidities requiring long-term/home oxygen use (e.g. severe chronic obstructive pulmonary disease [COPD], pulmonary fibrosis) or non-invasive ventilation (except for sleep apnea management), or making weaning per se improbable (e.g. ALS, muscular dystrophy)
• Smoke inhalation injury, extensive burns or trauma/head injury as concomitant condition
• History of pneumectomy, lung lobectomy or lung transplant
• Diffuse alveolar hemorrhage from vasculitis
• Current lung malignancy (incl. lung metastasis), or other malignancy requiring chemotherapy or radiation within the last month
• Chronic kidney disease with a history of renal replacement therapy (e.g. dialysis)
• Chronic liver disease Child-Pugh Class C
• Chronic heart failure NYHA IV
• Known hypersensitivity to polyethyleneglycol (PEG, Macrogol)
• Participation in other interventional studies involving pharmacological interventions, or biological or cell therapy interventions
• Diagnosis of COVID-19 pneumonia within 6 weeks prior to study inclusion. History of SARS-CoV-2 infection (positive test based on nucleic acid amplification technology or positive antigen test) without COVID-19 pneumonia does not exclude patients

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.