Study in Intensive Care Patients to Investigate the Clinical Effect of Repetitive Orally Inhaled Doses of AP301 on Alveolar Liquid Clearance in Acute Lung Injury

Proof of Concept Study in Male and Female Intensive Care Patients to Investigate the Clinical Effect of Repetitive Orally Inhaled Doses of AP301 on Alveolar Liquid Clearance in Acute Lung Injury

The purpose of this study is to assess the effect of orally inhaled AP301 on alveolar liquid clearance in ALI (acute lung injury) patients with the purpose to assess the treatment associated changes of extravascular lung water (EVLW) within 7 days of treatment.

Study Overview

• Status: Completed
• Conditions: Acute Lung Injury
• Intervention / Treatment: Drug: AP301; Drug: Saline solution

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Anesthesia, General Intensive Care and Pain Control,Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥ 18
• intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control
• meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS):
• Onset of ALI within 48 hours
• Bilateral infiltrates seen on frontal chest radiograph
• PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension
• paO2/ FiO2 ratio ≤ 300 mm Hg
• EVLW in PiCCO® at screening ≥ 8 ml/PBW
• Meeting criteria for extensive hemodynamic monitoring according to investigators discretion
• ICU Patients being mechanically ventilated and are stable in this condition for at least 8 hours
• Negative pregnancy test and adequate contraception in female patients of childbearing potential
• Informed consent:
• For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

Exclusion Criteria:

• History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product
• Brainstem death at screening
• Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure < 90 mm Hg or mean arterial pressure (MAP) < 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation)
• Neutrophil count <0.3 x 109 L
• Patients under immunosuppression: high dose steroids (> 80 mg Prednisolone /d; > 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks
• BMI < 18.5 or > 35
• Cardiogenic pulmonary edema diagnosed by echocardiography or pulmonary artery catheter
• Pregnancy / lactation or intention to fall pregnant during the time course of the study
• Women of childbearing potential as well as men of procreative capacity who are not using adequate contraception
• Participation in other interventional drug trials

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AP301; Treatment group	Drug: AP301; AP301 25 mg powder for reconstitution for solution for inhalation Orally delivered doses of 87.6 mg AP301 are inhaled every 12 hours (± 30 min), for a total of 7 days.
Placebo Comparator: saline solution; Placebo group	Drug: Saline solution; Placebo solution (0.9% physiologic NaCl) is inhaled 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
change in extravascular lung water within 7 days of treatment	EVWL (measured with PiCCO® technique) until day 7 of treatment (AUC)	change from baseline - day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenation index	Oxygenation index (PaO2 / FiO2 ratio) until day 7 of treatment	baseline - day 7
ventilator plateau pressure	Ventilator plateau pressure until day 7 of treatment	baseline - day 7
Murray Lung Injury Score		baseline - day 7
Ventilation parameters / lung function		baseline - day 7
Presence/absence/severity and duration of adverse effects - number and severity of adverse events (AEs), serious adverse events (SAEs) and suspected unexpected serious adverse events (SUSARs))		baseline - day 7

Collaborators and Investigators

• Sponsor: Apeptico Forschung und Entwicklung GmbH
• Investigators: Principal Investigator: Roman Ullrich, Prof., Medical University of Vienna

Publications and helpful links

General Publications

• Krenn K, Lucas R, Croize A, Boehme S, Klein KU, Hermann R, Markstaller K, Ullrich R. Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial. Crit Care. 2017 Jul 27;21(1):194. doi: 10.1186/s13054-017-1795-x.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: June 22, 2012
• First Posted (Estimate): June 26, 2012

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 15, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Peptide
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Wounds and Injuries; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: AP301-II-001; 2012-001863-64 (EudraCT Number)