Clinical trial NCT04949386: Safety, Tolerability and Efficacy of S-1226 in Post-COVID-19 Subjects With Persistent Respiratory Symptoms.
Official title: A Randomized, Placebo-Controlled Phase II Study To Evaluate The Safety, Tolerability And Efficacy Of S-1226 In Post-Covid-19 Subjects With Persistent Respiratory Symptoms.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Post Acute COVID-19 Syndrome
Long COVID
COVID-19 Respiratory Infection
Keywords: S-1226
Prolonged post viral respiratory symptoms
Lead sponsor: SolAeroMed Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-02
Enrollment: 48
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 (1:1) , placebo-controlled phase II study to evaluate the safety, tolerability and efficacy of S-1226 in Post-COVID-19 subjects (n≤48) with persistent respiratory symptoms. Subjects will receive twice daily treatments of either Placebo or S-1226 (8%) for 7 days.

Detailed description: This is a randomized, placebo-controlled, phase II proof of concept study to evaluate the safety, tolerability and efficacy of S-1226 in Post-COVID-19 subjects (n≤48) with persistent respiratory symptoms.

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, vapor and liquid aerosol penetrates obstructed airways, resulting in rapid bronchodilation, enhanced blood oxygenation, improved mucus clearance and reduction of work of breathing.

Primary objective of this study is to evaluate the safety and tolerability of S-1226 composed of perflubron with 8% carbon dioxide in subjects with persistent post acute COVID-19 respiratory symptoms. The secondary objective is to establish proof of concept that S-1226 is effective in normalizing lung symptoms, including cough, breathlessness and lung function in subjects with persistent post-acute COVID-19 respiratory symptoms.

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

1. Screening, and randomization: subjects will be randomized (1:1) to either receive placebo or S-1226 treatment.
2. Treatment and evaluation period: subjects will receive either placebo -medical grade air with 3ml saline (0.9% NaCl) - or S-1226 (8% CO2) for 7 days twice daily. A single dose of S1226 (8%) will be administered over 3-4 minutes at each visit. Subjects will have the option to receive at home treatments once they been trained and verified as competent in handling study equipment.
3. A follow up period 7 days after final treatment.

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. Able to provide informed consent.
  3. Prior confirmed COVID-19 diagnosis by standard Real time Polymerase Chain Reaction (RT-PCR) assay or Immunoglobin M/G (IgM/IgG) rapid serological test at least 4 weeks prior to screening visit.
  4. Ambulatory patients may be attending COVID long term follow up clinic or discharged from hospital for at least one week.
  5. Evidence of new and/or persistent respiratory symptoms at least 4 weeks after the onset of acute COVID-19 infection. This will be determined by history of respiratory symptoms: cough, wheeze, limitation of activities.
  6. Able to perform an exercise of moderate activity e.g., walking up a hill or climbing stairs (required to assess Borg RPE)
  7. Able to walk unaided for a minimum distance of 10 meters (distance validated for completion of 6-minute walk test)

Exclusion Criteria:

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

  1. Pregnancy or of childbearing age without a highly effective method or at least two forms of effective contraception and/ or abstinence for the duration of study. Highly effective methods of contraception (Contraception with \< 1% failure rate) are: hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Effective methods of contraception may include barrier methods of contraception (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge).
  2. Breastfeeding females.
  3. Evidence of active thromboembolic disorder - defined by those receiving parenteral anticoagulant or thrombolytic therapy.
  4. Pre-existing evidence of unstable angina and myocardial infraction during the previous month, contraindications to the 6MWT.
  5. Subject, who in the opinion of the Investigator, is unsuitable to participate.

Primary outcomes:
measure: Treatment Emergent Adverse Effects
timeFrame: 16 days
Secondary outcomes:
measure: Normalization in 6-minute walk test (6MWT) distance
timeFrame: 16 days
measure: Changes in percent predicted forced expiratory volume in 1 second
timeFrame: 16 days
measure: Changes in from baseline in respiratory symptoms assessed by the St George's Respiratory Questionnaire (SGRQ).
timeFrame: 16 days
Other outcomes:
measure: Change from baseline in Forced Vital Capacity.
timeFrame: 16 days
measure: Changes from baseline in Diffusing Lung Capacity
timeFrame: 16 days
measure: Changes from baseline in Oxygen Saturation (SpO2)
timeFrame: 16 days
measure: Changes in from baseline in respiratory symptoms assessed by the modified Medical Research Council (mMRC) scale of dyspnea during daily activity.
timeFrame: 16 days
measure: Changes in from baseline in respiratory symptoms assessed by the Borg Rating of Perceived Exertion (RPE) for dyspnea during exertion.
timeFrame: 16 days
measure: Changes in from baseline in respiratory symptoms assessed by Visual Analogue Scale (VAS) for dyspnea while at rest.
timeFrame: 16 days
Locations:
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.