Clinical Trial to Assess the Efficacy and Safety of Inhaled AQ001S in the Management of Acute COVID-19 Symptoms (SIROCCO-1)

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

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

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Drug, inhalation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liege, Belgium, 4000
    • Chu Liege

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:

1. Patient admitted to hospital due to the severity of his/her confirmed or suspected COVID-19 disease.
2. Positive virus test for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using real time polymerase chain reaction (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, 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:

1. Intensive care patients
2. Inability to use a nebulizer with a mouthpiece.
3. History of hypersensitivity to corticosteroid or to any of the excipients in the drug preparation.
4. Untreated oral candidiasis.
5. Evidence of symptomatic chronic or acute respiratory infection other than COVID-19 in the previous 8 weeks.
6. Proven diagnosis of Chronic Obstructive Pulmonary Disease, asthma or bronchiectasis.
7. Pulmonary malformations, tuberculosis, cystic fibrosis.
8. History or presence of severe renal (stage 4 (GFR = 15-29 mL/min)) and/or severe hepatic impairment(s) (grade 4 or above)
9. Anticipated transfer to another hospital within 72 hours.
10. Use of inhaled corticosteroid, at a strength at least equivalent to 200 µg of beclomethasone per day, within 7 days before Screening Visit.
11. Systemic corticosteroids (e.g., dexamethasone) within 28 days before Screening Visit.
12. Female patients who are breast-feeding, lactating, pregnant or intending to become pregnant.
13. 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.
14. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental AQ001S 0.125 mg/mL quarter in die; AQ001S 0.125 mg/mL inhalation solution administered by inhalation 4 times a day	Drug: Drug, inhalation; Solution administered by inhalation; Other Names: inhaled drug, including placebo
Experimental: Experimental AQ001S 0.125 mg/mL bis in die; AQ001S 0.125 mg/mL inhalation solution administered by inhalation twice a day + placebo by inhalation twice a day	Drug: Drug, inhalation; Solution administered by inhalation; Other Names: inhaled drug, including placebo
Placebo Comparator: Comparator: placebo; No active drug - administered by inhalation 4 times a day	Drug: Drug, inhalation; Solution administered by inhalation; Other Names: inhaled drug, including placebo

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change immune system response	Changes in the immune system response will be measured from baseline (Visit 2) to Day 28±2 (Visit 5), using a 15-plex Human Cytokine Panel assay.	After 28 days of treatment
Change in monocyte count	Changes in monocyte count will be measured from baseline (Visit 2) to Day 28±2 (Visit 5).	After 28 days of treatment
Change in lymphocyte count	Changes in lymphocyte count will be measured from baseline (Visit 2) to Day 28±2 (Visit 5).	After 28 days of treatment
Change in hyperinflammation biomarker: ferritin	Changes in hyperinflammation biomarkers will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Change in hyperinflammation biomarker: C reactive protein	Changes in hyperinflammation biomarkers will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Change in hyperinflammation biomarker: d-dimer	Changes in hyperinflammation biomarkers will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Change in hyperinflammation biomarker: soluble cluster of differentiation 40 ligand	Changes in hyperinflammation biomarkers will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Change in hyperinflammation biomarker: matrix metalloproteinase	Changes in hyperinflammation biomarkers will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Change in cardiovascular biomarker: troponin	Changes in troponin level will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Change in cardiovascular biomarker: creatine kinase	Changes increatine kinase level will be measured from baseline (Visit 2) to Day 7±2 (Visit 3), Day 14±2 (Visit 4) and Day 28±2.	After 28 days of treatment
Immunology parameters: immunoglobulin E	Changes in immunoglobulin E rates from baseline (Visit 2) to Day 28±2 (Visit 5), and at each visit over the dosing period	After 28 days of treatment
Immunology parameters: immunoglobulin A	Changes in immunoglobulin A rates from baseline (Visit 2) to Day 28±2 (Visit 5), and at each visit over the dosing period	After 28 days of treatment
Immunology parameters: immunoglobulin G	Changes in immunoglobulin G rates from baseline (Visit 2) to Day 28±2 (Visit 5), and at each visit over the dosing period	After 28 days of treatment

Collaborators and Investigators

• Sponsor: Aquilon Pharmaceuticals S.A.
• Investigators: Principal Investigator: Julien Guiot, MD, Centre hospitalier universitaire de Liege

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2021
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): December 21, 2022

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: August 10, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Estimate): January 6, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: AQ-PRO-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No