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

NCT03567577 | Completed Phase 2 DMC

• 1 other identifier: AP301-II-002
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 15

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

Keywords

Peptide

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• EVLWI

  baseline - day 7

• PVPI

  baseline - day 7

• Change of ventilatory settings

  baseline - day 14

• Murray lung injury score

  baseline - day 7

• Oxygenation ratio (PaO2 / FiO2 ratio)

  baseline - day 7

Study Arms (4)

Solnatide 5mg

EXPERIMENTAL

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

Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation

Solnatide 60mg

EXPERIMENTAL

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

Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation

Solnatide 125mg

EXPERIMENTAL

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

Drug: Solnatide 25 mg powder for reconstitution for solution for inhalation

Placebo

PLACEBO COMPARATOR

0,9% saline solution

Drug: 0.9% Saline Solution

Interventions

Solnatide 25 mg powder for reconstitution for solution for inhalation DRUG

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

Also known as: AP301

Solnatide 125mg; Solnatide 5mg; Solnatide 60mg

0.9% Saline Solution DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Male or female ≥18 years of age.
• 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.
• 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.
• ARDS diagnosis not older than 48 hours.
• Extravascular lung water index (EVLWI) ≥ 10 ml/PBW as assessed with a validated bedside measurement (single indicator transpulmonary thermodilution measurement with the PiCCO® system).
• Patient who meets criteria for extensive hemodynamic monitoring as per international intensive care medicine standards.
• For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.
• Male and Female (WOCBP) patients using adequate contraception.

You may not qualify if:

• History of clinically relevant allergies or idiosyncrasies to solnatide.
• Known use of any other investigational or non-registered drug within 30 days prior to study enrolment.
• 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.
• 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).
• Neutrophil count \< 0.3 x 109/L.
• Cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks.
• Cachexia (BMI \< 18.5 kg/m2).
• Cardiogenic pulmonary oedema diagnosed by echocardiography or pulmonary artery catheter.
• Severe skin burns involving more than 15% of body surface.
• 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.
• Subjects transferred from a hospital not participating in this study who are already planned to be re-transferred during the observation period.
• Subjects who are not expected to survive the next month because of an underlying uncorrectable medical condition or a do not resuscitate order.
• Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.

Sponsors & Collaborators

• Apeptico Forschung und Entwicklung GmbH: lead

Study Sites (15)

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

Graz, Styria, 8036, Austria

Location

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

Vienna, Vienna, 1090, Austria

Location

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

Innsbruck, 6020, Austria

Location

Klinik für Anaesthesiologie, Klinikum der Universität München, Campus Großhadern

München, Bavaria, 81377, Germany

Location

Klinik für Operative Intensivmedizin und Intermediate Care

Aachen, North Rhine-Westphalia, 52074, Germany

Location

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

Dresden, Saxony, 01307, Germany

Location

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

Bonn, 53127, Germany

Location

Georg-August-Universität Göttingen

Göttingen, 37075, Germany

Location

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

Kiel, 24105, Germany

Location

Klinik für Anästhesiologie / Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Klinik für Anästhesiologie und operative Intensivmedizin; Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

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

München, 81675, Germany

Location

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

München, 81675, Germany

Location

Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie; Universitätsklinikum Münster

Münster, 48149, Germany

Location

Universitätsklinikum Würzburg, Klinik und Poliklinik für Anästhesiologie

Würzburg, 97080, Germany

Location

MeSH Terms

Interventions

AP301 peptide; Powders; Solutions; Inhalation; Saline Solution

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Crystalloid Solutions; Isotonic Solutions

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: June 26, 2018
• Study Start: May 23, 2018
• Primary Completion: December 27, 2024
• Study Completion: December 27, 2024
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); DE (12)