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Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS

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ClinicalTrials.gov Identifier: NCT03567577
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
Apeptico Forschung und Entwicklung GmbH

Brief Summary:
This phase IIb, randomized, placebo-controlled, double-blind, dose escalation study will assess the local and systemic safety of 7 days orally inhaled sequential multiple ascending doses of solnatide in patients with pulmonary permeability oedema and moderate-to-severe ARDS and review potential efficacy endpoints for a future phase III pivotal trial.

Condition or disease Intervention/treatment Phase
ARDS Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation Drug: 0.9% Saline Solution Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS - a Randomised, Placebo-controlled, Double-blind Trial
Actual Study Start Date : May 23, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arm Intervention/treatment
Experimental: Solnatide 5mg
Solnatide 25 mg powder for reconstitution for solution for inhalation. 5mg administered
Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation
Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.
Other Name: AP301

Experimental: Solnatide 60mg
Solnatide 25 mg powder for reconstitution for solution for inhalation. 60mg administered
Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation
Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.
Other Name: AP301

Experimental: Solnatide 125mg
Solnatide 25 mg powder for reconstitution for solution for inhalation. 125mg administered
Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation
Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.
Other Name: AP301

Placebo Comparator: Placebo
0,9% saline solution
Drug: 0.9% Saline Solution
Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.




Primary Outcome Measures :
  1. Safety endpoint: Any cause death [ Time Frame: Randomisation - day 28 ]
    Primary Safety Endpoint: Composite endpoint including any cause death at day 28

  2. Safety endpoint: Drug-related adverse events [ Time Frame: Randomisation - day 14 ]
    Primary Safety Endpoint: Composite endpoint including drug-related adverse events through day 14

  3. Safety endpoint: All adverse events [ Time Frame: Randomisation - day 28 ]
    Primary Safety Endpoint: Composite endpoint including all adverse events through day 28


Secondary Outcome Measures :
  1. EVLWI [ Time Frame: baseline - day 7 ]
    Change in extravascular lung water index (EVLWI) as assessed with a validated bedside measurement (measurement with the PiCCO® system)

  2. PVPI [ Time Frame: baseline - day 7 ]
    Change in pulmonary vascular permeability index (PVPI) as assessed with a validated bedside measurement (measurement with the PiCCO® system)

  3. Change of ventilatory settings [ Time Frame: baseline - day 14 ]
    Composite endpoint including ventilation mode, ventilation pressures (ventilatory plateau pressure, positive end expiratory pressure, peak inspiratory pressure, mean airway pressure, peak airway pressure, driving pressure), tidal volume

  4. Murray lung injury score [ Time Frame: baseline - day 7 ]
    Murray lung injury score is composed of four components: 1) chest radiograph; 2) hypoxaemia score; 3) PEEP and 4) static compliance of respiratory system. The values of the total score may range from 0 to 4. Lower values indicate a better outcome.

  5. Oxygenation ratio (PaO2 / FiO2 ratio) [ Time Frame: baseline - day 7 ]
  6. Time to extubation [ Time Frame: baseline - day 28 ]
  7. Ventilator-free days (VFD) [ Time Frame: baseline - day 28 ]
  8. Days of hospitalization and in ICU [ Time Frame: baseline - day 28 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent
  2. Male or female ≥18 years of age.
  3. Patient has been admitted to an ICU, is mechanically ventilated (according to the ventilation and weaning protocol in Appendix I) and stable in this condition for at least 8 hours.
  4. Moderate-to-severe ARDS diagnosis as defined by the Berlin Definition:

    • Onset of ARDS within 1 week of a known clinical insult or new or worsening respiratory symptoms.
    • Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.
    • Respiratory failure not fully explained by cardiac failure or fluid overload (origin of oedema).
    • PaO2/FiO2 ≤ 200 mm Hg with Positive End-Expiratory Pressure (PEEP) ≥5 cm H2O.
  5. ARDS diagnosis not older than 48 hours.
  6. Extravascular lung water index (EVLWI) ≥ 10 ml/PBW as assessed with a validated bedside measurement (single indicator transpulmonary thermodilution measurement with the PiCCO® system).
  7. Patient who meets criteria for extensive hemodynamic monitoring as per international intensive care medicine standards.
  8. For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.
  9. Male and Female (WOCBP) patients using adequate contraception.

Exclusion Criteria:

  1. History of clinically relevant allergies or idiosyncrasies to solnatide.
  2. Known use of any other investigational or non-registered drug within 30 days prior to study enrolment.
  3. Severe state of septic shock with a Mean Arterial Pressure (MAP) ≤ 65 mm Hg and a serum lactate level > 4 mmol/L (36 mg/dL) despite adequate volume resuscitation.
  4. An underlying clinical condition that, in the opinion of the Investigator, would make it very unlikely for the patient to be successfully weaned from ventilation due to severe underlying diseases (e.g. severe malnutrition, severe neurological diseases, pulmonary fibrosis or COPD).
  5. Extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support. In no way are patients to be denied or delayed these procedures to avoid exclusion from the study.
  6. Neutrophil count < 0.3 x 109/L.
  7. Cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks.
  8. Cachexia (BMI < 18.5 kg/m2).
  9. Cardiogenic pulmonary oedema diagnosed by echocardiography or pulmonary artery catheter.
  10. Severe skin burns involving more than 15% of body surface.
  11. Subjects who are extremely unlikely to survive more than 48 hours due to the acute conditions of the patient in the opinion of the Investigator.
  12. Subjects transferred from a hospital not participating in this study who are already planned to be re-transferred during the observation period.
  13. Subjects who are not expected to survive the next month because of an underlying uncorrectable medical condition or a do not resuscitate order.
  14. Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03567577


Contacts
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Contact: Bernhard Fischer, Prof. Dr. 0043-664143 ext 2919 b.fischer@apeptico.com
Contact: Roman Ullrich, Prof. Dr.

Locations
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Austria
Univ.-klinik f. Herz-, Thorax-, Gefäßchirurgische Anästhesiologie und lntensivmedizin, Medizinische Universität Graz Recruiting
Graz, Steiermark, Austria, 8036
Contact: Bernhard Fischer, Doz.    0043-664143 ext 2919    b.fischer@apeptico.com   
Principal Investigator: Michael Schörghuber, Dr. med.         
Univ. Klinik für Innere Medizin / Gem. Einrichtung für Intensiv- und Notfallmedizin/GE Medizinische Universität Innsbruck Recruiting
Innsbruck, Austria, 6020
Contact: Bernhard Fischer, Doz.         
Principal Investigator: Michael Joannidis, Prof.         
Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Bernhard Fischer, Doz.    0043-664143 ext 2919    b.fischer@apeptico.com   
Principal Investigator: Roman Ullrich, Prof.         
Germany
Klinik für Anaesthesiologie, Klinikum der Universität München, Campus Großhadern Recruiting
München, Bayern, Germany, 81377
Contact: Bernhard Fischer, Doz.         
Principal Investigator: Sandra Frank, PD Dr.         
Klinik für Operative Intensivmedizin und Intermediate Care Recruiting
Aachen, Nordrhein-Westfalen, Germany, 52074
Contact: Bernhard Fischer, Doz         
Principal Investigator: Tim-Philipp Simon, PD Dr.         
Universitätsklinikum Bonn, Operative Intensivmedizin, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin Recruiting
Bonn, Germany, 53127
Contact: Bernhard Fischer, Doz.         
Principal Investigator: Christian Putensen, Prof.         
Klinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Recruiting
Kiel, Germany, 24105
Contact: Bernhard Fischer, Doz.         
Principal Investigator: Norbert Weiler, Prof.         
Klinik für Anästhesiologie / Universitätsmedizin der Johannes Gutenberg-Universität Mainz Recruiting
Mainz, Germany, 55131
Contact: Bernhard Fischer, Doz.         
Principal Investigator: Erik Hartmann, PD Dr.         
Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie Recruiting
Würzburg, Germany, 97080
Contact: Bernhard Fischer, Doz.         
Principal Investigator: Markus Kredel, Dr.         
Sponsors and Collaborators
Apeptico Forschung und Entwicklung GmbH
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Responsible Party: Apeptico Forschung und Entwicklung GmbH
ClinicalTrials.gov Identifier: NCT03567577    
Other Study ID Numbers: AP301-II-002
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Apeptico Forschung und Entwicklung GmbH:
Peptide
Additional relevant MeSH terms:
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Pharmaceutical Solutions