Clinical trial NCT04738136: Safety, Tolerability and Efficacy Of S-1226 in Moderate Severity Covid-19 Bronchiolitis/Pneumonia
Official title: A Randomized, Open-Label, Controlled, Phase II Study to Evaluate the Safety, Tolerability and Efficacy Of S-1226 In Hospitalized Subjects With Moderate Severity Covid-19 Bronchiolitis/Pneumonia
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Covid19
SARS-CoV-2 Infection
Keywords: S-1226
Moderate Severity Covid-19 infection
SolAeroMed
SARS-CoV-2
Lead sponsor: SolAeroMed Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, controlled, Phase II proof of concept study to evaluate the safety, tolerability and efficacy of S-1226 in which hospitalized subjects (n≤30) with moderate severity COVID-19 Bronchiolitis/Pneumonia will be enrolled. The safety and tolerability of S-1226 composed of PFOB with ascending doses of carbon dioxide (4%, 8%, and 12% CO2) administered twice daily will be assessed subjects in hospitalized subjects with moderate severity COVID-19 Bronchiolitis/Pneumonia.

Detailed description: This is a randomized, open-label, controlled, Phase II proof of concept study to evaluate the safety, tolerability and efficacy of S-1226 in which hospitalized subjects with moderate severity COVID-19 Bronchiolitis/Pneumonia.

S-1226 contains a potent, safe and well-tolerated bronchodilator gas (extrinsic carbon dioxide or CO2) and perflubron (PFOB), a synthetic surfactant that facilitates restoration of surfactant function and mucus clearance. The inhaled S-1226 combination of gas, vapour and liquid aerosol penetrates obstructed airways, resulting in rapid bronchodilation, enhanced blood oxygenation, improved mucus clearance and reduction of work of breathing

The primary objective of this study is to evaluate the safety and tolerability of S-1226 composed of perflubron (PFOB) with ascending doses of carbon dioxide (4%, 8% and 12% CO2) in hospitalized subjects with moderate severity COVID-19 bronchiolitis/pneumonia. The secondary objective is to establish proof of concept that S-1226 is effective in restoring lung function in hospitalized subjects with moderate severity COVID-19 bronchiolitis/pneumonia.

The study will consist of three parts: screening period, Dosing and evaluation, follow up period.

1. During the screening period, subjects will undergo safety assessments and their eligibility to participate will be confirmed. Eligible subjects will then be randomly assigned to either the treatment arm (S-1226 + Standard of Care arm) or the non-treatment arm (Standard of Care only).
2. The dosing and evaluation period will take place over 5 days of with two doses per day. Subjects who are randomized to receive S-1226 will be started on a dose level of S-1226 (4%). If tolerated, subjects will progress from 4%, followed by 8%, and then 12%. The highest tolerated dose will then be used for the remainder of the treatment period. All doses incorporate 3mL PFOB and will be administered over a 3-4 minute treatment period. Any enrolled subject randomized to receive S-1226 will not be required to interrupt any SOC treatment which includes supplementary oxygen.

   Each S-1226 dose will be administered as inhaled gas \& vapour using a Circulaire II hybrid system specifically adapted with the addition of an absolute aerosol filter installed at the site of aerosol generation. This filter removes all perflubron aerosol so that in this trial the S-1226 Gaseous Delivery System delivers an inhaled drug comprising gas (CO2 in air) and vapour (perflubron). In addition, the S-1226 Gaseous Delivery System includes a high efficiency bacterial/viral filter to scavenge any patient-generated exhaled aerosol.
3. Follow up Period will 28 days after the first dose of S1226 has been administered.

Eligibility criteria: Inclusion Criteria:

* Subjects must meet the following criteria to be included in the study:

  1. Male or Females between 18-80 years of age at the time of consent.
  2. Laboratory-confirmed COVID-19 infection
  3. Hospitalized for COVID-19 with clinical evidence of respiratory involvement, including at least one of the following:

     1. Symptoms/Signs: cough, respiratory distress, increased work of breathing
     2. Radiology: Chest radiograph or other chest imaging demonstrating one of bronchial thickening, increased secretions, hyperinflation, infiltrates
  4. Hypoxemia in room air, SpO2 ≤ 90%
  5. Patient belongs to one of the following two categories in the seven-point COVID-19 severity scale:

     1. Requiring supplemental oxygen by nasal prongs - Level 4 of the seven-point COVID-19 severity scale;
     2. Requiring nasal high-flow oxygen therapy,- limited to this one component of Level 5 of the seven-point COVID-19 severity scale.
  6. For women of childbearing potential involved in any sexual intercourse that could lead to pregnancy: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during the study period.
  7. Ability to sign informed consent or, when patient is not capable of doing so, informed consent can be signed by legal/authorized representative

Exclusion Criteria:

* Subjects to whom any of the following applies will be excluded from the study:

  1. Pregnant or breastfeeding females.
  2. Patients unable to receive S-1226; particularly if receiving oxygen therapy by face mask or non invasive ventilatory support
  3. Patient requires Extracorporeal Membrane Oxygenation (ECMO) and/or invasive mechanical ventilation
  4. Presence of any of the following abnormal laboratory values at screening:

     1. Absolute neutrophil count (ANC) less than 0.5 x 109 / L.
     2. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN).
     3. Platelets less than 50 x109 / L.
  5. In the opinion of the investigator, progression to death is imminent and inevitable within the next 72 hours, irrespective of the provision of treatment.
  6. Subject, who in the opinion of the Investigator, is unsuitable to participate

Primary outcomes:
measure: Treatment Emergent Adverse Effects
timeFrame: up to 28 days
Secondary outcomes:
measure: Change in use of supplemental oxygen therapy
timeFrame: up to 28 days
measure: Normalization of body temperature, measured in degrees Celsius.
timeFrame: up to 28 days
measure: Evaluation of changes in an SpO2/FiO2 ratio
timeFrame: up to 28 days
measure: Mean change on a 7-point ordinal scale
timeFrame: up to 28 days
measure: Proportion of patients that progress to levels 6-7 of the 7-point Ordinal Scale
timeFrame: up to 28 days
measure: Time to progression to levels 6-7 of the 7-point Ordinal Scale
timeFrame: up to 28 days
measure: Normalization of oxygen saturation, SpO2 > 90%, while breathing room air, sustained minimum 24 hours
timeFrame: up to 28 days
measure: Time to normalization of oxygen saturation, SpO2 > 90%, while breathing room air sustained minimum 24 hours.
timeFrame: up to 28 days
measure: Change in daily symptom monitoring assessed by yes or no questions to a list of symptoms.
timeFrame: up to 6 days
measure: Days of hospitalization attributable to COVID-19 disease
timeFrame: up to 28 days
Other outcomes:
measure: Improvement in Thoracic Imaging as assessed by a Radiologist
timeFrame: up to 28 days
measure: Number of Participants that develop of secondary pneumonia.
timeFrame: up to 28 days
measure: Viral load
timeFrame: up to 28 days
Locations:
city: Calgary
country: Canada
facility: Alberta Lung Function
state: Alberta
Study officials:
affiliation: University of Calgary
name: Mark Montgomery, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Swystun V, Green FHY, Dennis JH, Rampakakis E, Lalli G, Fadayomi M, Chiu A, Shrestha G, El Shahat SG, Nelson DE, El Mays TY, Pieron CA, Leigh R. A phase IIa proof-of-concept, placebo-controlled, randomized, double-blind, crossover, single-dose clinical trial of a new class of bronchodilator for acute asthma. Trials. 2018 Jun 18;19(1):321. doi: 10.1186/s13063-018-2720-6.
citation: Green FH, Leigh R, Fadayomi M, Lalli G, Chiu A, Shrestha G, ElShahat SG, Nelson DE, El Mays TY, Pieron CA, Dennis JH. A phase I, placebo-controlled, randomized, double-blind, single ascending dose-ranging study to evaluate the safety and tolerability of a novel biophysical bronchodilator (S-1226) administered by nebulization in healthy volunteers. Trials. 2016 Jul 28;17:361. doi: 10.1186/s13063-016-1489-8.
citation: El Mays TY, Choudhury P, Leigh R, Koumoundouros E, Van der Velden J, Shrestha G, Pieron CA, Dennis JH, Green FH, Snibson KJ. Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma. Respir Res. 2014 Sep 16;15(1):98. doi: 10.1186/s12931-014-0098-x.