This Study Collects Information on the Safety of Inhaled Pegylated Adrenomedullin (PEG-ADM), How the Drug is Tolerated and How it Affects Patients Suffering From a Type of Lung Failure That Cause Fluid to Build up in the Lungs Making Breathing Difficult (ARDS)

NCT04417036 | Terminated Phase 2 DMC

• 2 other identifiers: 199992019-001078-27
• Study Type: interventional
• Target: 90
• Locations: 7 countries
• Sites: 22

Brief Summary

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.

Conditions

Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (1)

• VFS in Part B participants

  Ventilator-free survival (VFS, participants alive and not on invasive mechanical ventilation)

  At Day 28

Secondary Outcomes (7)

• CUI in Part A participants

  Up to 7 days

• VFS in Part A participants

  At Day 28

• All-cause mortality in Part A and Part B participants

  At Day 28, Day 60 and Day 90

• Proportion of participants who still require invasive mechanical ventilation support in Part A and Part B participants

  At Day 28 and Day 60

• Ventilator-free days (VFDs) in Part A and Part B participants

  Within Day 28 and Day 60

Study Arms (5)

Part A - Active Drug Dose 1

EXPERIMENTAL

Participants will receive Active Drug Dose 1 for a maximum of 14 days in study phase Part A

Drug: BAY1097761 Active Dose 1

Part A - Active Drug Dose 2

EXPERIMENTAL

Participants will receive Active Drug Dose 2 for a maximum of 14 days in study phase Part A

Drug: BAY1097761 Active Dose 2

Part A - Placebo

PLACEBO COMPARATOR

Participants will receive Placebo for a maximum of 14 days in study phase Part A

Other: Placebo to BAY1097761

Part B - Active Drug Dose

EXPERIMENTAL

Participants will receive Active Drug 1 or 2 for a maximum of 14 days in study phase Part B

Drug: BAY1097761 Active Dose 1; Drug: BAY1097761 Active Dose 2

Part B - Placebo

PLACEBO COMPARATOR

Participants will receive Placebo for a maximum of 14 days in study phase Part B

Other: Placebo to BAY1097761

Interventions

BAY1097761 Active Dose 1 DRUG

Participants will receive a lower dose ADM by inhalation

Part A - Active Drug Dose 1; Part B - Active Drug Dose

Placebo to BAY1097761 OTHER

Participants will receive Placebo to BAY1097761 by inhalation

Part A - Placebo; Part B - Placebo

BAY1097761 Active Dose 2 DRUG

Participants will receive a higher dose ADM by inhalation

Part A - Active Drug Dose 2; Part B - Active Drug Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (22)

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Universitätsklinikum AKH Wien

Vienna, 1090, Austria

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Masaryk Hospital Usti n/L

Ústí nad Labem, 401 13, Czechia

Location

Centre Hospitalier Universitaire - Angers

Angers, 49933, France

Location

Center Hospitalier Michallon - Grenoble

La Tronche, 38700, France

Location

Hôpital du Nord - Marseille

Marseille, 13915, France

Location

Hôpital de la Pitié-Salpétrière

Paris, 75013, France

Location

Cochin - Paris

Paris, 75014, France

Location

Hôpital Civil - Strasbourg

Strasbourg, 67091, France

Location

Klinikum Oldenburg AöR

Oldenburg, Lower Saxony, 26133, Germany

Location

Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim

Cologne, North Rhine-Westphalia, 51109, Germany

Location

Universitätsklinikum Schleswig-Holstein (UKSH)

Kiel, Schleswig-Holstein, 24105, Germany

Location

Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.

Milan, Lombardy, 20089, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

ASST Santi Paolo e Carlo

Milan, Lombardy, 20142, Italy

Location

Corporació Sanitària Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i de Sant Pau

Barcelona, 08041, Spain

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (1)

• Karagiannidis C, McAuley DF, Thompson BT, Reimer T, Shakery K, Schmitz S, Cortes MN, Ullrich R, Meziani F, Mercat A, Chiumello D, Duska F, Combes A; SEAL Trial Investigators. Safety and efficacy of inhaled PEG-ADM in ARDS patients: a randomised controlled trial. Crit Care. 2025 Oct 23;29(1):448. doi: 10.1186/s13054-025-05617-y.

  PMID: 41131549 DERIVED

Related Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 4, 2020
• Study Start: July 7, 2020
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: April 18, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6); IT (3); GB (2); DE (3); CZ (3); AU (2); ES (3)