Back to resultsSafety, Tolerability and Efficacy of S-1226 in Post-COVID-19 Subjects With Persistent Respiratory Symptoms.
Primary Purpose
Post Acute COVID-19 Syndrome, Long COVID, COVID-19 Respiratory Infection
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
S-1226 (8%)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Post Acute COVID-19 Syndrome focused on measuring S-1226, Prolonged post viral respiratory symptoms
Eligibility Criteria
Inclusion Criteria:
Subjects must meet the following criteria to be included in the study:
- Male or Females between 18 -80 years of age at the time of consent
- Able to provide informed consent.
- 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.
- Ambulatory patients may be attending COVID long term follow up clinic or discharged from hospital for at least one week.
- 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.
- Able to perform an exercise of moderate activity e.g., walking up a hill or climbing stairs (required to assess Borg RPE)
- 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:
- 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).
- Breastfeeding females.
- Evidence of active thromboembolic disorder - defined by those receiving parenteral anticoagulant or thrombolytic therapy.
- Pre-existing evidence of unstable angina and myocardial infraction during the previous month, contraindications to the 6MWT.
- Subject, who in the opinion of the Investigator, is unsuitable to participate.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment with S-1226 (8%)
Placebo
Arm Description
Subjects randomized to this treatment arm will receive S-1226(8%) twice daily for 7 consecutive days. S-1226 will be administered by inhalation for 3-4 minutes.
Subjects randomized to receive placebo will be administered with medical grade air with 3ml saline (0.9% NaCl) using the Circulaire II hybrid system. Placebo will be administered by inhalation for 3-4 minutes.
Outcomes
Primary Outcome Measures
Treatment Emergent Adverse Effects
The number and percent of treatment emergent adverse events will be monitored, recorded and graded for severity and assigned attribution. The severity will be assessed in the following manner:
Mild: Awareness of signs or symptoms, but are easily tolerated and are of minor irritant type, causing no limitations of usual activities. Signs or symptoms may require minor action or additional therapy.
Moderate: Discomfort severe enough to cause some limitations of usual activities and may require action or additional therapy.
Severe: Incapacitating with inability to carry out usual activities and requires specific action and/or medical attention. Note: the term severe is not the same as "serious", which is based on subject/event outcome or action criteria usually associated with events that pose a threat to a subject's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.
Secondary Outcome Measures
Normalization in 6-minute walk test (6MWT) distance
Changes in induced shortness of breath will be monitored using the 6 Minute walk test (6MWT) with continuous oxygen saturation (SpO2) monitoring . Normalization will be assessed by a return to normal distance values established in the literature.
Changes in percent predicted forced expiratory volume in 1 second
Change from baseline in percent of predicted forced expiratory volume in 1 Second (FEV1) will be calculated by measuring FEV1 at baseline and after treatment. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
Changes in from baseline in respiratory symptoms assessed by the St George's Respiratory Questionnaire (SGRQ).
St George's Respiratory Questionnaire (SGRQ), a two-part questionnaire that evaluates participant symptoms, including cough, (part 1) and activities and impact (part 2). Scores range from 0 to100 with higher scores indicating more limitations/perceived distress. Scores will be compared to the established minimally clinically important difference (MCID).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04949386
Brief Title
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
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
September 2021 (Anticipated)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
January 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SolAeroMed Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Screening, and randomization: subjects will be randomized (1:1) to either receive placebo or S-1226 treatment.
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.
A follow up period 7 days after final treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Acute COVID-19 Syndrome, Long COVID, COVID-19 Respiratory Infection
Keywords
S-1226, Prolonged post viral respiratory symptoms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment with S-1226 (8%)
Arm Type
Experimental
Arm Description
Subjects randomized to this treatment arm will receive S-1226(8%) twice daily for 7 consecutive days. S-1226 will be administered by inhalation for 3-4 minutes.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to receive placebo will be administered with medical grade air with 3ml saline (0.9% NaCl) using the Circulaire II hybrid system. Placebo will be administered by inhalation for 3-4 minutes.
Intervention Type
Drug
Intervention Name(s)
S-1226 (8%)
Other Intervention Name(s)
S-1226
Intervention Description
S-1226 has two components delivered by inhalation. It is a mixture of perfluorooctylbromide (PFOB) delivered in gas/aerosol/vapor form within a medical gas mixture containing 8% CO2.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo will delivered by inhalation of saline (0.9% NaCl) and Medical grade air.
Primary Outcome Measure Information:
Title
Treatment Emergent Adverse Effects
Description
The number and percent of treatment emergent adverse events will be monitored, recorded and graded for severity and assigned attribution. The severity will be assessed in the following manner:
Mild: Awareness of signs or symptoms, but are easily tolerated and are of minor irritant type, causing no limitations of usual activities. Signs or symptoms may require minor action or additional therapy.
Moderate: Discomfort severe enough to cause some limitations of usual activities and may require action or additional therapy.
Severe: Incapacitating with inability to carry out usual activities and requires specific action and/or medical attention. Note: the term severe is not the same as "serious", which is based on subject/event outcome or action criteria usually associated with events that pose a threat to a subject's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.
Time Frame
16 days
Secondary Outcome Measure Information:
Title
Normalization in 6-minute walk test (6MWT) distance
Description
Changes in induced shortness of breath will be monitored using the 6 Minute walk test (6MWT) with continuous oxygen saturation (SpO2) monitoring . Normalization will be assessed by a return to normal distance values established in the literature.
Time Frame
16 days
Title
Changes in percent predicted forced expiratory volume in 1 second
Description
Change from baseline in percent of predicted forced expiratory volume in 1 Second (FEV1) will be calculated by measuring FEV1 at baseline and after treatment. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
Time Frame
16 days
Title
Changes in from baseline in respiratory symptoms assessed by the St George's Respiratory Questionnaire (SGRQ).
Description
St George's Respiratory Questionnaire (SGRQ), a two-part questionnaire that evaluates participant symptoms, including cough, (part 1) and activities and impact (part 2). Scores range from 0 to100 with higher scores indicating more limitations/perceived distress. Scores will be compared to the established minimally clinically important difference (MCID).
Time Frame
16 days
Other Pre-specified Outcome Measures:
Title
Change from baseline in Forced Vital Capacity.
Description
Change from baseline in Forced Vital Capacity (FVC) will be measured. FVC is the total volume of air that can be exhaled during a maximal forced expiration effort.
Time Frame
16 days
Title
Changes from baseline in Diffusing Lung Capacity
Description
Changes from Baseline in Diffusing lung capacity (DLCO) will be measures. DLCO is a measurement used to evaluate the lungs ability to transfer gas from inspired air to the bloodstream.
Time Frame
16 days
Title
Changes from baseline in Oxygen Saturation (SpO2)
Description
Changes from baseline in percent of oxygen saturation (measured by pulse oximetry) will be calculated by measuring oxygen saturation before and up to 30 minutes after treatment.
Time Frame
16 days
Title
Changes in from baseline in respiratory symptoms assessed by the modified Medical Research Council (mMRC) scale of dyspnea during daily activity.
Description
The modified Medical Research Council (mMRC) scale of dyspnea used assess baseline and subsequent activity related dyspnea. Scores range from 0-4, with increasing scores representing greater difficulty in performing daily activities.
Time Frame
16 days
Title
Changes in from baseline in respiratory symptoms assessed by the Borg Rating of Perceived Exertion (RPE) for dyspnea during exertion.
Description
Borg Rating of Perceived Exertion (RPE) a categorical scale used to assess dyspnea during exertion. The lowest score, 6, represents No exertion/effort at all while the highest score of 20 represents absolute maximal effort/exhaustion.
Time Frame
16 days
Title
Changes in from baseline in respiratory symptoms assessed by Visual Analogue Scale (VAS) for dyspnea while at rest.
Description
A 10 cm Visual Analogue Scale (VAS) to assess participant dyspnea while at rest at the time of Assessment. Three delineations will be placed on the scale (0 being no dyspnea, 5 (middle) and 10 being max dyspnea) for participants to mark with a cross.
Time Frame
16 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must meet the following criteria to be included in the study:
Male or Females between 18 -80 years of age at the time of consent
Able to provide informed consent.
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.
Ambulatory patients may be attending COVID long term follow up clinic or discharged from hospital for at least one week.
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.
Able to perform an exercise of moderate activity e.g., walking up a hill or climbing stairs (required to assess Borg RPE)
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:
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).
Breastfeeding females.
Evidence of active thromboembolic disorder - defined by those receiving parenteral anticoagulant or thrombolytic therapy.
Pre-existing evidence of unstable angina and myocardial infraction during the previous month, contraindications to the 6MWT.
Subject, who in the opinion of the Investigator, is unsuitable to participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Dennis, PhD
Phone
403-689-5989
Email
jdennis@solaeromed.com
First Name & Middle Initial & Last Name or Official Title & Degree
Francis Green, MBChB, MD
Phone
403-220-4514
Email
fgreen@ucalgary.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Montgomery, MD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29914544
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.
Results Reference
background
PubMed Identifier
27464582
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.
Results Reference
background
PubMed Identifier
25355286
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.
Results Reference
background
Links:
URL
http://www.solaeromed.com
Description
Website of the sponsoring company
Learn more about this trial
Safety, Tolerability and Efficacy of S-1226 in Post-COVID-19 Subjects With Persistent Respiratory Symptoms.
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