Clinical Trial to Assess the Efficacy and Safety of Inhaled AQ001S in the Management of Acute COVID-19 Symptoms

Study Overview
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Brief Summary
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Double-blind parallel trial to assess the efficacy and safety of inhaled AQ001S in the management of acute COVID-19 symptoms compared.

Detailed Description
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A randomized, double-blind, placebo-controlled, parallel clinical trial to determine the safety and efficacy of inhaled AQ001S in the management of acute COVID-19 symptoms in adult patients (≥ 18 years old) who are admitted to hospital due to the severity of his/her confirmed or suspected COVID-19 disease. The patient will be treated for 28 days.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel, Trial to Determine the Safety and Efficacy of Inhaled AQ001S in the Management of Acute COVID-19 Symptoms

Conditions
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Covid19

Intervention / Treatment
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* Drug: Drug, inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient admitted to hospital due to the severity of his/her confirmed or suspected COVID-19 disease. Positive virus test for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using real time polymerase chain reaction (nasal swab). Patient with COVID-19 clinical progression scale score ≥ 4 (hospitalized; no oxygen therapy). Male or female, ≥18 years of age at the time of consent. Patients who have given written informed consent. Reliable patients who are willing to be available for the duration of the clinical trial and willing to comply with clinical trial procedures. Patients who have the ability to understand the requirements of the clinical trial. Female patients of childbearing potential (women of childbearing potential, WOCBP ) should have a negative pregnancy test at Screening Visit. Female patients of childbearing potential (women of childbearing potential, WOCBP1) using a highly effective method of contraception (i.e., pregnancy rate of < 1% per year) on a stable regimen, for at least 28 days, and pursuing this contraception during the trial and for 28 days after the last administration of the study drug The highly effective methods of contraception must be one of the following: combined estrogen and progestogen hormonal contraception with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or agreement on continuous abstinence from heterosexual intercourse. Exclusion Criteria: Intensive care patients Inability to use a nebulizer with a mouthpiece. History of hypersensitivity to corticosteroid or to any of the excipients in the drug preparation. Untreated oral candidiasis. Evidence of symptomatic chronic or acute respiratory infection other than COVID-19 in the previous 8 weeks. Proven diagnosis of Chronic Obstructive Pulmonary Disease, asthma or bronchiectasis. Pulmonary malformations, tuberculosis, cystic fibrosis. History or presence of severe renal (stage 4 (GFR = 15-29 mL/min)) and/or severe hepatic impairment(s) (grade 4 or above) Anticipated transfer to another hospital within 72 hours. Use of inhaled corticosteroid, at a strength at least equivalent to 200 µg of beclomethasone per day, within 7 days before Screening Visit. Systemic corticosteroids (e.g., dexamethasone) within 28 days before Screening Visit. Female patients who are breast-feeding, lactating, pregnant or intending to become pregnant. Any condition, including findings in the patients' medical history or in the pre-randomization study assessments that, in the opinion of the Investigator, constitute a risk or a contraindication for the participation of the patient into the study or that could interfere with the study objectives, conduct or evaluation. Current or previous participation in another clinical trial where the patient has received a dose of an study drug containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study

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: Experimental AQ001S 0.125 mg/mL quarter in die<br>AQ001S 0.125 mg/mL inhalation solution administered by inhalation 4 times a day | Drug: Drug, inhalation<br>* Solution administered by inhalation<br>* Other names: inhaled drug, including placebo;|
| Experimental: Experimental AQ001S 0.125 mg/mL bis in die<br>AQ001S 0.125 mg/mL inhalation solution administered by inhalation twice a day + placebo by inhalation twice a day | Drug: Drug, inhalation<br>* Solution administered by inhalation<br>* Other names: inhaled drug, including placebo;|
| Placebo Comparator: Comparator: placebo<br>No active drug - administered by inhalation 4 times a day | Drug: Drug, inhalation<br>* Solution administered by inhalation<br>* Other names: inhaled drug, including placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence of Treatment-Emergent Adverse Events as assessed by collection of (Serious) Adverse Events and general/local tolerability | During 28 days of treatment | 
| WHO clinical progression scale (COVID-19 clinical progression scale) | Change in the WHO clinical progression scale (reference: WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection, Lancet Infect Dis., Aug 2020, 20(8): e192-e197) with Uninfected as minimal value (e.g. 0) and Dead as maximal value (e.g. 10, worse outcome), ffrom baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to hospital discharge | Time to hospital ldischarge measured over the treatment period from baseline (visit 2) to day 28 (visit 5). | After 28 days of treatment | 
| Time to Intensive Care Unit admission | Time to Intensive Care Unit admission measured over the treatment period from baseline (visit 2) to day 28 (visit 5). | After 28 days of treatment | 
| Length of Intensive Care Unit stay | Length of Intensive Care Unit stay measured over the treatment period from baseline (visit 2) to day 28 (visit 5). | After 28 days of treatment | 
| Time to hospital readmission | Time to hospital readmission measured over the treatment period from baseline (visit 2) to day 28 (visit 5). | After 28 days of treatment | 
| Length of hospital readmission | Length of hospital readmission measured over the treatment period from baseline (visit 2) to day 28 (visit 5). | After 28 days of treatment | 
| Time to mechanical ventilation | Time to mechanical ventilation measured over the treatment period from baseline (visit 2) to day 28 (visit 5). | After 28 days of treatment | 
| Occurrence of death | Occurence of death (all deaths). | Within 60 days from hospitalisation | 
| Modified Medical Research Council Dyspnea Scale | Change in modified Medical Research Council Dyspnea (mMRC) Scale from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5). Minimum mMRC Scale value is 0 (e.g. I only get breathless with strenuous exercise). The maximum mMRC Scale value is 4 (e.g. I am too breathless to leave the house or I am breathless when dressing, worse outcome). | to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary function measurement: Forced Expiratory Volume in the first second (FEV1) | Changes in FEV1 measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary function measurement: Forced Vital Capacity (FVC) | Changes in FVC measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary function measurement: FEV1/FVC ratio | Changes in FEV1/FVC ratio from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary function measurement: Oxygen saturation (SpO2) | Changes in SpO2 measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary function measurement: Fraction of inspired Oxygen (FiO2) | Changes in FiO2 measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary function measurement: SpO2/FiO2 ratio | Changes in and SpO2/FiO2 ratio measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Diffusion Capacity for Carbon Monoxide measurements | Changes in the Diffusion Capacity for Carbon Monoxide (DLCO) from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2. | At Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2 (Visit 5) | 
| Pulmonary CT Scan | Changes in the pulmonary CT Scan between baseline (Visit 2) and Day 28±2 (Visit 5) | After 28 days of treatment |