Safety, Tolerability and Efficacy of S-1226 in Cystic Fibrosis and Non CF Bronchiectasis

NCT03903913 | Unknown Phase 2

• 1 other identifier: SAMi-03-1-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This is a single center, open label, Phase IIa, multiple-ascending dose study in which subjects with mild to moderate Cystic Fibrosis and non CF bronchiectasis (n≤12) 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 in subjects with Cystic Fibrosis and non CF bronchiectasis will be evaluated. This will be followed by 5 day consecutive treatment using the highest tolerated dose of S1226. Participants can choose additional use of a further four weeks (28 days) of S-1226 therapy at home, using same or a lower tolerated dose.

Conditions

Cystic Fibrosis; Bronchiectasis

Keywords

Asthma; Carbon dioxide; Perfluorocarbon; Mucolytic

Outcome Measures

Primary Outcomes (1)

• Treatment-emergent adverse events

  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.

  60 minutes

Secondary Outcomes (2)

• Change from baseline in percent of predicted forced expiratory volume in 1 Second

  60 minutes

• Change from baseline in the respiratory domain of Cystic Fibrosis Questionnaire -Revised

  Up to 4 weeks

Other Outcomes (8)

• Change from baseline in Forced Vital Capacity

  Up to 4 weeks

• Change from baseline in Forced Expiratory Flow at 25-75%

  Up to 4 weeks

• Change from baseline in Inspiratory Capacity

  Up to 4 weeks

Study Arms (2)

Dose Escalation Study

EXPERIMENTAL

Subjects will receive up to three inhaled doses of S- 1226. Each dose will be administered over a 2-minute treatment period (with a minimum 2-minute break between treatments) with a nebulizer as follows. Three S-1226 formulations will be tested sequentially: * S-1226(4%) is composed of 3 mL PFOB and 4% CO2 * S-1226(8%) is composed of 3 mL PFOB and 8% CO2 * S-1226(12%) is composed of 3 mL PFOB and 12% CO2 Each formulation will be administered by inhalation for a period of 2 minutes.The nebulizer will be filled with 3 mL of PFOB. The nebulizer is connected to a compressed medical gas mixture consisting of either 4%, 8% or 12%, CO2. A driving pressure of 20 psi will be used, producing a gas flow rate of 9 L/min.

Drug: S-1226

Daily Dosing Study

EXPERIMENTAL

Eligible subjects will receive S-1226 twice daily for 5 consecutive days. Subjects will receive up to three doses of S-1226 in the morning and afternoon, administered over three 2-minute periods with a Circulaire nebulizer, filled with one of the dosages outlined below, depending on the safety and tolerability data gathered from the dose escalation study for that particular subject. * S-1226(4%) is composed of 3 mL PFOB and 4% CO2 * S-1226(8%) is composed of 3 mL PFOB and 8% CO2 * S-1226(12%) is composed of 3 mL PFOB and 12% CO2

Drug: S-1226

Interventions

S-1226 DRUG

The drug product S-1226 has two components delivered by inhalation. It is a mixture of perfluorooctylbromide (PFOB) nebulized with a medical gas mixture containing CO2. The PFOB component remains the same but the medical gas component contains 4%, 8% or 12% CO2.

Also known as: S-1226 (4%), S-1226 (8%), S-1226 (12%)

Daily Dosing Study; Dose Escalation Study

Eligibility Criteria

• Age: 14 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Confirmed diagnosis of Cystic Fibrosis by sweat chloride concentration over 60 mosm/L and/or genotype analysis identifying two disease causing mutations
• Male or Female over the age of 14
• Followed in CF clinic at Foothills Hospital or Alberta Children's Hospital
• Known lung involvement
• Recommended airway clearance daily or twice daily
• FEV1, % predicted, between 40-80%
• Evidence of Cystic Fibrosis lung involvement on Imaging, if available
• Competent at providing reliable and accurate pulmonary function studies
• Clinically stable - no pulmonary exacerbation of CF for which the patient has been hospitalized or received intravenous antibiotics for 4 weeks, no change in frequency of airway clearance

You may not qualify if:

• Gross Hemoptysis in previous 4 weeks
• Pneumothorax in previous 4 weeks
• Pregnancy or of child bearing age without adequate contraception
• Inability to produce acceptable and reproducible pulmonary function studies
• Evidence of elevated PaCO2 in recent 6 months
• Inability to perform airway clearance twice a day for the duration of the study
• History of anxiety/panic disorders
• Breast-feeding subject.
• Positive pregnancy test at screening.
• Subject, who in the opinion of the Investigator, is mentally or emotionally unsuitable to participate, or unable/unwilling to comply with the study assessments.
• Gross Hemoptysis in previous 4 weeks Pneumothorax in previous 4 weeks Pregnancy or of child bearing age without adequate contraception Inability to produce acceptable and reproducible pulmonary function studies Evidence of elevated PaCO2 in recent 6 months Inability to perform airway clearance twice a day for the duration of the study History of anxiety/panic disorders Breast-feeding subject. Positive pregnancy test at screening. Subject, who in the opinion of the Investigator, is mentally or emotionally unsuitable to participate, or unable/unwilling to comply with the study assessments.
• Male or Female including and over the age of 14
• Known lung involvement
• FEV1, % predicted, between 40-80%
• Evidence of bronchiectasis on Imaging

Sponsors & Collaborators

• SolAeroMed Inc.: lead

Study Sites (3)

Adult Cystic Fibrosis Clinic at the Foothills Hospital

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

Pediatric Cystic Fibrosis Clinic at Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

Alberta Lung Function

Calgary, Alberta, Canada

NOT YET RECRUITING

Related Publications (3)

• 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.

  PMID: 29914544 BACKGROUND

• 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.

  PMID: 27464582 BACKGROUND

• 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.

  PMID: 25355286 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Bronchiectasis; Asthma

Interventions

perfluorooctylbromide and CO2 drug combination

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Mark Montgomery, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Dennis, Phd

CONTACT

403-689-5989; jdennis@solaeromed.com

Francis Green, MBChB, MD

CONTACT

403-220-4514; fgreen@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single center, open label, Phase IIa, sequential, multiple-ascending dose study

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: April 4, 2019
• Study Start: August 8, 2019
• Primary Completion: February 1, 2022
• Study Completion: August 1, 2022
• Last Updated: June 16, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)