Safety, Tolerability and Efficacy of S-1226 in Post-COVID-19 Subjects With Persistent Respiratory Symptoms.

Phase 2

• Conditions: COVID-19 Respiratory Infection; Post Acute COVID-19 Syndrome; Long COVID
• Interventions: Drug: S-1226 (8%); Other: Placebo

• Registration Number: NCT04949386
• Lead Sponsor: SolAeroMed Inc.

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.

Study Timeline

• Study First Submitted: 2021-06-30
• Study First Submitted QC: 2021-06-30
• Study First Posted: 2021-07-02
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-16
• Last Update Posted: 2021-08-23
• Study Start: 2021-09
• Primary Completion: 2021-12
• Study Completion: 2022-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 48

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment with S-1226 (8%)	S-1226 (8%)	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.
Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Effects	16 days	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

Name	Time	Method
Normalization in 6-minute walk test (6MWT) distance	16 days	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	16 days	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).	16 days	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).