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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Lung Injury

Intervention / Treatment
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* Drug: AP301
* Drug: Saline solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AP301<br>Treatment group | Drug: AP301<br>* 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.<br>|
| Placebo Comparator: saline solution<br>Placebo group | Drug: Saline solution<br>* Placebo solution (0.9% physiologic NaCl) is inhaled every 12 hours (± 30 min), for a total of 7 days.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peptide