Back to resultsStudy 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)
Primary Purpose
Acute Respiratory Distress Syndrome
Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
BAY1211163
Sponsored by
About this trial
This is an interventional treatment trial for Acute Respiratory Distress Syndrome
Eligibility Criteria
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.
Sites / Locations
- Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim
- Sana-Klinikum Remscheid|Kardio, Angio, Pneumo u. Intensivmed
- Charité - Universitätsmedizin Berlin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BAY1211163
Arm Description
Adult patients with moderate or severe Acute Respiratory Distress Syndrome (ARDS) diagnosis before study inclusion will receive BAY1211163.
Outcomes
Primary Outcome Measures
Numbers of participants with treatment emergent adverse events (TEAEs)
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.
Secondary Outcome Measures
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04609943
Brief Title
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)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Company Decision.
Study Start Date
November 24, 2020 (Actual)
Primary Completion Date
August 17, 2023 (Actual)
Study Completion Date
September 14, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BAY1211163
Arm Type
Experimental
Arm Description
Adult patients with moderate or severe Acute Respiratory Distress Syndrome (ARDS) diagnosis before study inclusion will receive BAY1211163.
Intervention Type
Drug
Intervention Name(s)
BAY1211163
Intervention Description
Participants will receive one of the drug doses of BAY1211163 solution three times per day (TID) by inhalation for seven days.
Primary Outcome Measure Information:
Title
Numbers of participants with treatment emergent adverse events (TEAEs)
Time Frame
Up to 9 days
Title
Numbers of participants with dose limiting events (DLEs)
Description
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.
Time Frame
Day 1 to 7 (may include Day 8)
Secondary Outcome Measure Information:
Title
Values of oxygenation index (OI)
Description
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)
Time Frame
Up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim
City
Köln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
51109
Country
Germany
Facility Name
Sana-Klinikum Remscheid|Kardio, Angio, Pneumo u. Intensivmed
City
Remscheid
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
42859
Country
Germany
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://clinicaltrials.bayer.com/
Description
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.
Learn more about this trial
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)
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