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

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ClinicalTrials.gov Identifier: NCT03903913
Recruitment Status : Recruiting
First Posted : April 4, 2019
Last Update Posted : June 16, 2021
Sponsor:
Information provided by (Responsible Party):
SolAeroMed Inc.

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.


Condition or disease Intervention/treatment Phase
Cystic Fibrosis Bronchiectasis Drug: S-1226 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single center, open label, Phase IIa, sequential, multiple-ascending dose study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIa Open Label Study to Evaluate the Safety, Tolerability and Efficacy of S-1226 Administered by Nebulization in Subjects With Mild to Moderate Cystic Fibrosis and Non CF Bronchiectasis
Actual Study Start Date : August 8, 2019
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Dose Escalation Study

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
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.
Other Names:
  • S-1226 (4%)
  • S-1226 (8%)
  • S-1226 (12%)

Experimental: Daily Dosing Study

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
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.
Other Names:
  • S-1226 (4%)
  • S-1226 (8%)
  • S-1226 (12%)




Primary Outcome Measures :
  1. Treatment-emergent adverse events [ Time Frame: 60 minutes ]

    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 :
  1. Change from baseline in percent of predicted forced expiratory volume in 1 Second [ Time Frame: 60 minutes ]
    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.

  2. Change from baseline in the respiratory domain of Cystic Fibrosis Questionnaire -Revised [ Time Frame: Up to 4 weeks ]
    Change from baseline in respiratory symptoms scores (subscale) of the Cystic Fibrosis Questionnaire -Revised (CFQ-R) will be measured. CFQ-R is a validated, disease specific, patient reported outcome measure used to evaluate the impact of CF on overall health, daily life, and perceived well-being and symptoms. This sub-scale ranges from scores of 0-100, with higher values representing a better outcome.


Other Outcome Measures:
  1. Change from baseline in Forced Vital Capacity [ Time Frame: Up to 4 weeks ]
    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.

  2. Change from baseline in Forced Expiratory Flow at 25-75% [ Time Frame: Up to 4 weeks ]
    Change from baseline in Forced Expiratory Flow at 25-75% (FEF25-75%) will be measured. FEF25-75% is defined as Forced expiratory flow over the middle one half of the Forced Vital Capacity (FVC); the average flow from the point at which 25 percent of the FVC has been exhaled to the point at which 75 percent of the FVC has been exhaled.

  3. Change from baseline in Inspiratory Capacity [ Time Frame: Up to 4 weeks ]
    Change from baseline in Inspiratory Capacity (IC) will be measured. IC is defined as the maximal volume of air that can be inhaled from the resting expiratory level.

  4. Change from baseline in Thoracic Gas Volume [ Time Frame: Up to 4 weeks ]
    Change from baseline in Thoracic Gas Volume (TGV) will be measured. TGV is defined as the absolute volume of gas in the thorax at any point in time and any level of alveolar pressure.

  5. Change from baseline in Residual Volume [ Time Frame: Up to 4 weeks ]
    Change from baseline in Residual Volume (RV) will be measured. RV is defined as the volume of air remaining in the lungs after a maximal exhalation.

  6. Change from baseline in Lung Clearance Index [ Time Frame: Up to 4 weeks ]
    Change from baseline in Lung Clearance Index will be measured. Lung clearance index is a unitless measurement, which is defined as the total volume of expired gas required to decrease the amount of the tracer gas to 1/40 of its initial concentration divided by the functional residual capacity. It is measure of ventilation inhomogeneity.

  7. Change in expectorated sputum volume [ Time Frame: 120 minutes ]
    Expectorated sputum volume (in milliliters) will be measured at baseline and after treatment and any changes in measured volume from baseline will be reported.

  8. Change from baseline in oxygen saturation [ Time Frame: 60 minutes ]
    Change from baseline in percent of oxygen saturation (measured by pulse oximetry) will be calculated by measuring oxygen saturation before and up to 60 minutes after treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   14 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criterian(CF lung disease):

  • 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

    1. Recommended airway clearance daily or twice daily
    2. FEV1, % predicted, between 40-80%
    3. 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

Exclusion Criteria CF lung disease:

  • 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.

Inclusion Criteria (Non-CF bronchiectasis)

  • Male or Female including and over the age of 14
  • Known lung involvement

    1. FEV1, % predicted, between 40-80%
    2. Evidence of bronchiectasis on Imaging
  • Competent at providing reliable and accurate pulmonary function studies
  • Clinically stable - no pulmonary exacerbation for which the patient has been hospitalized or received intravenous antibiotics for 4 weeks

Exclusion Criteria (Non-CF bronchiectasis)

  • Diagnosis of Cystic Fibrosis
  • Active tuberculosis and/or non-tuberculosis mycobacterial infection
  • Active allergic bronchopulmonary aspergillosis
  • Traction bronchiectasis due to pulmonary fibrosis
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03903913


Contacts
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Contact: John Dennis, Phd 403-689-5989 jdennis@solaeromed.com
Contact: Francis Green, MBChB, MD 403-220-4514 fgreen@ucalgary.ca

Locations
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Canada, Alberta
Adult Cystic Fibrosis Clinic at the Foothills Hospital Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Grishma Shrestha, MD    4032203044    grishma.shrestha@ucalgary.ca   
Pediatric Cystic Fibrosis Clinic at Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Grishma Shrestha, MD    4032203044    grishma.shrestha@ucalgary.ca   
Alberta Lung Function Not yet recruiting
Calgary, Alberta, Canada
Contact: Bryce Oslanski, RT    (403) 289-0723    Info@albertalungfunction.ca   
Principal Investigator: Mark Montgomery, MD         
Sponsors and Collaborators
SolAeroMed Inc.
Investigators
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Principal Investigator: Mark Montgomery, MD University of Calgary
Additional Information:
Publications:
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Responsible Party: SolAeroMed Inc.
ClinicalTrials.gov Identifier: NCT03903913    
Other Study ID Numbers: SAMi-03-1-01
First Posted: April 4, 2019    Key Record Dates
Last Update Posted: June 16, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SolAeroMed Inc.:
Asthma
Carbon dioxide
Perfluorocarbon
Mucolytic
Additional relevant MeSH terms:
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Cystic Fibrosis
Bronchiectasis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Bronchial Diseases