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

NCT ID: NCT03567577

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-23
• Study Completion Date: 2024-12-27

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.

Conditions

ARDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Solnatide 5mg

Solnatide 25 mg powder for reconstitution for solution for inhalation. 5mg administered

Group Type: EXPERIMENTAL

Solnatide 25 mg powder for reconstitution for solution for inhalation

Intervention Type: DRUG

Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.

Solnatide 60mg

Solnatide 25 mg powder for reconstitution for solution for inhalation. 60mg administered

Group Type: EXPERIMENTAL

Solnatide 25 mg powder for reconstitution for solution for inhalation

Intervention Type: DRUG

Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.

Solnatide 125mg

Solnatide 25 mg powder for reconstitution for solution for inhalation. 125mg administered

Group Type: EXPERIMENTAL

Solnatide 25 mg powder for reconstitution for solution for inhalation

Intervention Type: DRUG

Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.

Placebo

0,9% saline solution

Group Type: PLACEBO_COMPARATOR

0.9% Saline Solution

Intervention Type: DRUG

Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.

Interventions

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.

Intervention Type: DRUG

0.9% Saline Solution

Inhalation of an aerosol every 12 hours (± 30 min), for a total of 7 days.

Intervention Type: DRUG

Other Intervention Names

AP301

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apeptico Forschung und Entwicklung GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Univ.-klinik f. Herz-, Thorax-, Gefäßchirurgische Anästhesiologie und lntensivmedizin, Medizinische Universität Graz

Graz, Styria, Austria

Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna

Vienna, Vienna, Austria

Univ. Klinik für Innere Medizin / Gem. Einrichtung für Intensiv- und Notfallmedizin/GE Medizinische Universität Innsbruck

Innsbruck, , Austria

Klinik für Anaesthesiologie, Klinikum der Universität München, Campus Großhadern

München, Bavaria, Germany

Klinik für Operative Intensivmedizin und Intermediate Care

Aachen, North Rhine-Westphalia, Germany

Klinik und Poliklinik für Anästhesiologie und Intensivtherapie / Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Universitätsklinikum Bonn, Operative Intensivmedizin, Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin

Bonn, , Germany

Georg-August-Universität Göttingen

Göttingen, , Germany

Klinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel,

Kiel, , Germany

Klinik für Anästhesiologie / Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Klinik für Anästhesiologie und operative Intensivmedizin; Universitätsmedizin Mannheim

Mannheim, , Germany

Klinik für Anästhesiologie und Intensivmedizin; Klinikum rechts der Isar der TU München

München, , Germany

Klinik und Poliklinik für Innere Medizin II; Klinikum rechts der Isar der TU München

München, , Germany

Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie; Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie

Würzburg, , Germany

Countries

Austria; Germany

Other Identifiers

AP301-II-002

Identifier Type: -

Identifier Source: org_study_id