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

NCT ID: NCT04949386

Last Updated: 2021-08-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-30
• Study Completion Date: 2022-01-31

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.

Conditions

Post Acute COVID-19 Syndrome; Long COVID; COVID-19 Respiratory Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment with 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.

Group Type: EXPERIMENTAL

S-1226 (8%)

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will delivered by inhalation of saline (0.9% NaCl) and Medical grade air.

Interventions

S-1226 (8%)

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: DRUG

Placebo

Placebo will delivered by inhalation of saline (0.9% NaCl) and Medical grade air.

Intervention Type: OTHER

Other Intervention Names

S-1226

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SolAeroMed Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Montgomery, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Central Contacts

John Dennis, PhD

Role: CONTACT

jdennis@solaeromed.com

403-689-5989

Francis Green, MBChB, MD

Role: CONTACT

fgreen@ucalgary.ca

403-220-4514

References

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.

Reference Type: BACKGROUND

PMID: 29914544 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27464582 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25355286 (View on PubMed)

Other Identifiers

SAMi-06-1-01

Identifier Type: -

Identifier Source: org_study_id