A clinical study to assess the safety and efficacy of a liquid for inhalation of budesonide (AQ001S) to treat adults with COVID-19 related respiratory disease

INTERVENTION: Product Name: Budesonide inhalation solution 0.125 mg/ml Product Code: AQ001S 0.125 mg/ml Pharmaceutical Form: Inhalation solution INN or Proposed INN: BUDESONIDE CAS Number: 51333‐22‐3 Current Sponsor code: Budesonide Other descriptive name: 16a,17a ‐butylidenedioxy‐11ß,21‐dihydroxypregna‐1,4‐diene‐3,20‐dione Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 0.125‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Inhalation use CONDITION: COVID‐19 related respiratory disease ; MedDRA version: 23.0 Level: LLT Classification code 10084270 Term: SARS‐CoV‐2 acute respiratory disease System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] SECONDARY OUTCOME: Secondary end point(s): • Assesssment of 6‐minute walking test (6MWT) results at Day 28±2; • Changes in nocturnal oximetry from baseline (Visit 2) to Day 28±2; • Changes in Saint‐Georges’ questionnaire from baseline (Visit 2) to Day 28±2; • Change in VAS chest pain from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2; • Changes in ACQ‐5 quality of life questionnaire from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2.; • Measurement of the level of circulating exosomes in blood at baseline (Visit 2) and Day 7±2, Day 14±2, Day 28±2.; • Measurement of the level of circulating fibrocytes in blood at baseline (Visit 2) and Day 7±2, Day 14±2, Day 28±2.; Timepoint(s) of evaluation of this end point: At visits 2 (Baseline), 3 (Week 1), 4 (Week 2) and 5 (Day 28). See Endpoint description for more information.; INCLUSION CRITERIA: 1. Patient admitted to hospital due to the severity of his/her confirmed or suspected COVID‐19 disease. 2. Positive virus test for SARS‐CoV‐2 using RT‐PCR (nasal swab). 3. Patient with COVID‐19 clinical progression scale score = 4 (hospitalized; no oxygen therapy). 4. Male or female, =18 years of age at the time of consent. 5. Patients who have given written informed consent. 6. Reliable patients who are willing to be available for the duration of the clinical trial and willing to comply with clinical trial procedures. 7. Patients who have the ability to understand the requirements of the clinical trial. 8. Female patients of childbearing potential (women of childbearing potential, WOCBP) should have a negative pregnancy test at Screening Visit. 9. Female patients of childbearing potential (women of childbearing potential, WOCBP) using a highly effective method of contraception (i.e., pregnancy rate of < 1% per year) on a stable regimen, PRIMARY OUTCOME: Main Objective: To assess the safety of AQ001S in the management of acute COVID‐19 symptoms; To assess the efficacy of AQ001S in the management of acute COVID‐19 symptoms; To assess the effects of AQ001S on pharmacodynamic (PD) parameters related to COVID‐19; Primary end point(s): The safety will be evaluated collecting the following information:; • Adverse events and serious adverse events ; • General tolerability: vital signs, ECG, physical examination (including signs of hypercorticism and adrenal suppression) ; • Laboratory parameters: hematology, biochemistry and urinalysis ; • Safety and tolerability ‐ respiratory rate ; • Safety and tolerability ‐ oxygen saturation; • Local tolerability: ; o Increased bronchial irritability ; o Paradoxical bronchospasm; o Oropharyngeal examination (e.g. vocal cord myopathy, fungal infection); ; The efficacy will be evaluated collecting the following information:; • Change in the COVID‐19 clinical progression scale from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2.; • changes in COVID‐19 clinical endpoints from baseline (Visit 2) to Day 28 ±2, and over the dosing period:; o Time to discharge,; o Time to ICU admission,; o Length of ICU stay,; o Time to hospital readmission.; o Length of hospital readmission ; o Time to mechanical ventilation ; o Occurrence of death within 60 days; • Change in mMRC (Modified Medical Research Council) Dyspnea Scale from baseline (Visit 2) at Day 28±2; • Changes in the pulmonary function (Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, SpO2, FiO2 and SpO2/FiO2 ratio) from baseline (Visit 2) to Day 28±2 ; • Changes in the diffusion capacity for carbon monoxide (DLCO) from baseline (Visit 2) to Day 28±2 ; • Changes in the pulmonary CT Scan from baseline (Visit 2) to Day 28±2; ; The PD will be evaluated collecting the following information:; • Changes in the systemic inflammatory and cardiovascular biomarkers from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2:; o Inflammatory markers: IL‐1 ß, IL‐4, IL‐6, IL‐10, IL‐17A, IL‐17F, IL‐21, IL‐22, IL‐23, IL‐25, IL‐31, IL‐33, TNFa, ferritin, CRP, d‐dimer, neutrophil count, macrophage count, lymphocyte count, eosinophil count, Neutrophil Extracellular Trap (NET) production, IFN‐?, sCD40L; o Cardiovascular markers: Troponin, CK, MMPs (MMP1, MMP9, MMP8, MMP12, MMP13) ; • Changes in IgE, IgA and IgG rates from baseline (Visit 2) to Day 28±2 Secondary Objective: Not applicable Timepoint(s) of evaluation of this end point: At visits 2 (Baseline), 3 (Week 1), 4 (Week 2) and 5 (Day 28). See Endpoint description for more information.; Efficacy: change from baseline; Safety: descriptive comparison with baseline