Study to Find the Highest Safe Dose of Soluble Guanylate Cyclase (sGC) Activator, BAY 1211163 Administered as Multiple Doses by Inhalation to Patients Who Cannot Breathe by Their Own and Suffer From a Type of Lung Failure That Causes Fluid to Build up in the Lungs Making Breathing Difficult (ARDS)

Safety and Tolerability of Adaptive Escalating Multiple Doses (Three Times Daily) of a Soluble Guanylate Cyclase (sGC) Activator Inhale, BAY 1211163, as Inhalation in Intubated and Mechanically Ventilated Adult Patients With Moderate and Severe Acute Respiratory Distress Syndrome (ARDS). A Pilot (Phase Ib), First in Patient, Open Label Study

With this study researchers want to find the highest safe dose of the soluble Guanylate Cyclase (sGC) Activator, BAY 1211163 and how safe and well the study drug works. Furthermore researchers want to gather information on the way the body absorbs, distributes and gets rid of the study drug given as increasing multiple doses by inhalation to patients who cannot breathe by their own and suffer from a type of lung failure that causes fluid to build up in the lungs making breathing difficult (ARDS)

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: BAY1211163

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 51109
      • Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim
    • Remscheid, Nordrhein-Westfalen, Germany, 42859
      • Sana-Klinikum Remscheid|Kardio, Angio, Pneumo u. Intensivmed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Intubated, mechanically ventilated moderate or severe ARDS patients [diagnosed according to Berlin definition of ARDS, including PEEP ≥ 5 cmH2O, X-ray, with PaO2/FiO2 between 80 and 200 mmHg (inclusive).
• Initial diagnosis of ARDS prior to study inclusion, confirmation of ongoing moderate or severe ARDS with PaO2/FiO2 between 80 and 200 mmHg (inclusive) during this time under maintained invasive mechanical ventilation.
• Hypoxemia with PaO2/FiO2 between 80 and 200 mmHg (inclusive) maintained for at least 8 hours (recommend to be 12 hours) after screening, despite consent to follow recommendation on ventilator strategy and PEEP management.
• Time from intubation must be ≤ 96h.
• Male and non-pregnant female.
• Informed consent of capable patient or, in case of patient being incapable of giving informed consent, consent for study inclusion will be sought according to applicable laws and regulations.

Exclusion Criteria:

• PaO2/FiO2 > 200 mmHg or < 80 mmHg at time of evaluation for inclusion.
• Moribund participants not expected to survive 24 hours (clinical decision).
• Expected duration of invasive mechanical ventilation less than 96 hours (clinical decision).
• History of pneumectomy or lung transplant.
• Current lung malignancy (including lung metastasis), or other malignancy requiring chemotherapy or radiation within the last month.
• History of chronic kidney disease and requiring renal replacement therapy dialysis at screening and/or baseline.
• Chronic liver disease Child-Pugh Class B and C.
• Hypoalbuminemia - serum albumin < 2.0 g/dL.
• Acute left ventricular failure and/or Left Ventricular Ejection Fraction < 30 %.
• Severe bronchopulmonal fistula.
• Clinical suspicion of pulmonary veno-occlusive disease.
• Heart right-sided endocarditis, tumors or mass.
• Rescue procedures already initiated at screening and/or Day 1.
• Use of co-medications involving moderate and strong inhibitors for CYP2C8 liver enzymes one week before assignment to intervention or during intervention.
• Off-label use of medication to treat Coronavirus SARS-CoV-2 virus unless recommended by scientific guidelines and accepted by DMC, investigator and sponsor.
• Plan to participate or past participation (within 30 days prior to Study Day 1) in other interventional studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1211163; Adult patients with moderate or severe Acute Respiratory Distress Syndrome (ARDS) diagnosis before study inclusion will receive BAY1211163.	Drug: BAY1211163; Participants will receive one of the drug doses of BAY1211163 solution three times per day (TID) by inhalation for seven days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of participants with treatment emergent adverse events (TEAEs)		Up to 9 days
Numbers of participants with dose limiting events (DLEs)	A dose limiting event is defined as any of the TEAEs occurring during dosing with BAY1211163 and regarded by the investigators to be related to BAY1211163.	Day 1 to 7 (may include Day 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Values of oxygenation index (OI)	The Oxygenation Index (OI) is calculated by using the fraction of inspired oxygen (FiO2), the partial pressure of oxygen in arterial blood (PaO2) and the mean airway pressure (MPAW)	Up to 28 days

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): August 17, 2023
• Study Completion (Actual): September 14, 2023

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 20425; 2019-004950-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No