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

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

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.

Study Overview

• Status: Recruiting
• Conditions: ARDS
• Intervention / Treatment: Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation; Drug: 0.9% Saline Solution

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bernhard Fischer, Prof. Dr.; Phone Number: 2919 0043-664143; Email: b.fischer@apeptico.com

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • Univ. Klinik für Innere Medizin / Gem. Einrichtung für Intensiv- und Notfallmedizin/GE Medizinische Universität Innsbruck
    • Contact: Bernhard Fischer, Doz.
    • Principal Investigator: Michael Joannidis, Prof.
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna
    • Contact: Bernhard Fischer, Doz.; Phone Number: 2919 0043-664143; Email: b.fischer@apeptico.com
    • Principal Investigator: Katharina Krenn, Dr
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Active, not recruiting
      • Univ.-klinik f. Herz-, Thorax-, Gefäßchirurgische Anästhesiologie und lntensivmedizin, Medizinische Universität Graz
• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • Universitätsklinikum Bonn, Operative Intensivmedizin, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin
    • Contact: Bernhard Fischer, Doz.
    • Principal Investigator: Christian Putensen, Prof.
  • Göttingen, Germany, 37075
    • Recruiting
    • Georg-August-Universität Göttingen
    • Contact: Bernhard Fischer, Doz
    • Principal Investigator: Onnen Mörer, Prof.
  • Kiel, Germany, 24105
    • Active, not recruiting
    • Klinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel,
  • Mainz, Germany, 55131
    • Terminated
    • Klinik für Anästhesiologie / Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Mannheim, Germany, 68167
    • Recruiting
    • Klinik für Anästhesiologie und operative Intensivmedizin; Universitätsmedizin Mannheim
    • Contact: Bernhard Fischer, Doz
    • Principal Investigator: Jörg Krebs, Prof
  • München, Germany, 81675
    • Recruiting
    • Klinik für Anästhesiologie und Intensivmedizin; Klinikum rechts der Isar der TU München
    • Contact: Bernhard Fischer, Doz
    • Principal Investigator: Markus Heim, PD Dr. med.
  • München, Germany, 81675
    • Recruiting
    • Klinik und Poliklinik für Innere Medizin II; Klinikum rechts der Isar der TU München
    • Contact: Bernhard Fischer, Doz
    • Principal Investigator: Tobias Lahmer, Prof
  • Münster, Germany, 48149
    • Recruiting
    • Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie; Universitätsklinikum Münster
    • Contact: Bernhard Fischer, Doz
    • Principal Investigator: Alexander Zarbock, Prof
  • Würzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie
    • Contact: Bernhard Fischer, Doz.
    • Principal Investigator: Peter Kranke, Dr.
  • Bayern
    • München, Bayern, Germany, 81377
      • Recruiting
      • Klinik für Anaesthesiologie, Klinikum der Universität München, Campus Großhadern
      • Principal Investigator: Sandra Frank, PD Dr.
      • Contact: Bernhard Fischer, Doz.
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Recruiting
      • Klinik für Operative Intensivmedizin und Intermediate Care
      • Contact: Bernhard Fischer, Doz
      • Principal Investigator: Tim-Philipp Simon, PD Dr.
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Recruiting
      • Klinik und Poliklinik für Anästhesiologie und Intensivtherapie / Universitätsklinikum Carl Gustav Carus
      • Contact: Bernhard Fischer, Doz
      • Principal Investigator: Peter Spieth, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoint: Any cause death	Primary Safety Endpoint: Composite endpoint including any cause death at day 28	Randomisation - day 28
Safety endpoint: Drug-related adverse events	Primary Safety Endpoint: Composite endpoint including drug-related adverse events through day 14	Randomisation - day 14
Safety endpoint: All adverse events	Primary Safety Endpoint: Composite endpoint including all adverse events through day 28	Randomisation - day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EVLWI	Change in extravascular lung water index (EVLWI) as assessed with a validated bedside measurement (measurement with the PiCCO® system)	baseline - day 7
PVPI	Change in pulmonary vascular permeability index (PVPI) as assessed with a validated bedside measurement (measurement with the PiCCO® system)	baseline - day 7
Change of ventilatory settings	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	baseline - day 14
Murray lung injury score	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.	baseline - day 7
Oxygenation ratio (PaO2 / FiO2 ratio)		baseline - day 7
Time to extubation		baseline - day 28
Ventilator-free days (VFD)		baseline - day 28
Days of hospitalization and in ICU		baseline - day 28

Collaborators and Investigators

• Sponsor: Apeptico Forschung und Entwicklung GmbH

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 23, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Peptide
• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: AP301-II-002

Drug and device information, study documents

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