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

Learn more about:
Related Clinical Trial
Microbial Colonization Distribution and Adaptive Evolution of Lower Respiratory Tract in Bronchiectasis Patients. Safety, Tolerability and Efficacy of S-1226 in Cystic Fibrosis and Non CF Bronchiectasis Is a Single Daily Session Combining HS and ACTs Sufficient to Obtain Long-term Clinical Benefits in Bronchiectasis? Bacille Calmette-Guerin (BCG) Vaccine for Immune Protection Against Infections Investigation of Dynamic Hyperinflation and Its Relationship With Functional Exercise Capacity in Children With Bronchiectasis COmmunity Patients at Risk of Viral Infections Including SARS-CoV-2 Integrating Electronic Patient Reported Biometric Measures (ePReBMs) From Wearable Devices in Respiratory Diseases Role of Pseudomonas Aeruginosa Biofilms in Exacerbations in Patients With Bronchiectasis With and Without Chronic Obstructive Pulmonary Disease Trial on The Efficacy of Hypertonic Saline on Non-CF CSLD. Evaluation of the Effect of Yoga Training on Functional Capacity and Quality of Life in Patients With Bronchiectasis Effect of Long Term Clarithromycin for Prevention of Exacerbations in Non-cystic Fibrosis Bronchiectasis in Asian Populations A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method A Prospective Study of Factors Related to Exacerbation and Mortality of Non-cystic Fibrosis Bronchiectasis in Hong Kong Efficacy and Safety of Inhaled Bronchodilator in Non-CF Bronchiectasis With Airflow Limitation Efficacy and Safety of An’Ningpai Expectorant in Non-CF Bronchiectasis COVID-19 Phobia in Patients With Bronchiectasis During Covid-19 Pandemic Identification of Microbiome of Bronchiectasis in Chinese Population. Lung Damage Caused by SARS-CoV-2 Pneumonia (COVID-19) Lidocaine Administration During Flexible Bronchoscopy and Endobronchial Ultrasound COPD Patient-Powered Research Network Can we Reduce Hospital Attendance Without Compromising Care by the Use of Telephone Consultation Sustained Effects of Hypertonic Saline on Mucociliary Clearance in Subjects With Chronic Bronchitis Seoul National University Airway Registry VX-770 for the Treatment of Chronic Bronchitis Etiologies, Investigations and Outcomes of Patients Presenting With Hemoptysis Adherence to Airway Clearance. Novel Approaches to Improving Adherence Inhaled Molgramostim (rhGM-CSF) in Healthy Adult Subjects Prevalence of Respiratory Impairment During IBD The SENSOR Study: A Mixed-methods Study of SElf-management Checks to Predict exacerbatioNs of Pseudomonas Aeruginosa in Patients With Long-term reSpiratORy Conditions The Effect of Proprioceptive Neuromuscular Facilitation (PNF) Technique for Children With Chronic Pulmonary Diseases. Effect of HFCWO Vests on Spirometry Measurements Effect of High Frequency Chest Wall Oscillation Vests on Spirometry Measurements Epidemiology and Diagnosis of Haemoptysis: a Multicenter Study Evaluating the Effects of Traditional Chinese Medicine by N-of-1 Trials A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Food Effect of Single or Repeat Doses of GSK2793660 in Healthy Subjects Biological Determinants of Sputum Rheology in Chronic Airway Diseases A Pilot Study to Investigate Administration of Mannitol Via a Novel Dry Powder Inhaler Device Efficacy and Safety Study of a Percussion Device to Mobilise Sputum From Respiratory Passage ATP and Capsaicin Cough Provocation Test in Chronic Cough and Bronchiectasis Summative Usability Study of Ciprofloxacin Dry Powder for Inhalation Using Placebo Lung Clearance Index (LCI) in Pediatric Patients With Obstructive Lung Disease The Prevalence of Gastro-oesophageal Reflux in Chronic Lung Disease High Dose Inhaled Mannitol Study Macrolide Mediates Pulmonary Infection of Pseudomonas Aeruginosa Respiratory Muscle Strength in Bronchiectasis: Repeatability and Reliability Longitudinal Study of Helium-3 and Xenon-129 Magnetic Resonance Imaging The Effect of Long Term Therapy With High Flow Humidification Compared to Usual Care in Patients With Bronchiectasis (BX) Evaluation Of The Lung Microbiome In NTM Bronchiectasis Inhalation Flow Rate-study Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis Bronchiectasis in Chronic Obstructive Pulmonary Disease (COPD) Patients: Role of Prophylaxis Procalcitonin-Guided Antibiotic Therapy in Bronchiectasis Inspiratory Flow and Volumes in Bronchiectatics Evaluation of Oscillatory Positive Expiratory Pressure (oPEP) in Bronchiectasis and COPD Evaluation of Periodontal Treatment in Patients With Bronchiectasis Long Term Nebulised Gentamicin in Patients With Bronchiectasis Comparison of PR Efficiency in Home-based With Hospital-based PR in Bronchiectasis Safety, Efficacy and PK/PD of POL7080 in Patients With Exacerbation of Non-cystic Fibrosis Bronchiectasis. Study of the Effect of FLUTTER® VRP1 (PEP and Oscillating High Frequency). Comparisons of Inhaled LAMA or LAMA+LABA or ICS+LABA for COPD With Bronchiectasis A Trial of Atorvastatin as an Anti-Inflammatory Agent in Non-Cystic Fibrosis Bronchiectasis Effects of Chest Physiotherapy (CPT) on Lung Clearance Index (LCI) in Non Cystic Fibrosis (CF) Bronchiectasis Randomised Open Label Trial of Hypertonic Saline and Carbocisteine in Bronchiectasis (CLEAR) Tobramycin in Bronchiectasis Colonized With Pseudmonas Aeruginosa Pulmonary Rehabilitation in Non Cystic Fibrosis Bronchiectasis Therapy of Bronchoalveolar Lavage and Local Amikacin Injection in Patients With Acute Exacerbation of Bronchiectasis Physiological Effects of Expiration With the Glottis Open in Lateral Posture (ELTGOL) and Flutter Valve in Patients With Bronchiectasis Comparison of the Efficacy of Comprehensive Respiratory Physiotherapy in Children With Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis Safety and Efficacy of Oral BAY85-8501 in Patients With Non-CF (Cystic Fibrosis) Bronchiectasis Safety and Tolerability Study of 2 Dose Level of Arikayce™ in Patients With Bronchiectasis and Chronic Infection Due to Pseudomonas Aeruginosa. Expert Patient Self-management Programme Versus Usual Care in Bronchiectasis The Long Term Effect of Inhaled Hypertonic Saline (6%) in Patients With Non Cystic Fibrosis Bronchiectasis Sputum Clearance Effects of Hypertonic Saline in Non-cystic Fibrosis Bronchiectasis Safety and Efficacy of Bronchitol in Bronchiectasis Predictors of Physical Activity Performance and Dynamic Hyperinflation in Patients With Bronchiectasis Oscillating PEP vs Autogenic Drainage in People With Bronchiectasis Feasibility of Interval Exercise in Bronchiectasis Prognosis of Bronchiectasis in Children–A Multicenter Prospective Cohort Study Exercise Training in Patients With Non-cystic Fibrosis (CF) Bronchiectasis Effects of Inspiratory Muscle Training in Patients With Bronchiectasis Acute Effects of a Flutter Device and Chest Wall Compression on Respiratory System Impedance in Bronchiectasis Patients Vitamin D as an Adjunctive Treatment in Patients With Non-Cystic Fibrosis Bronchiectasis Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis Cardiovascular Comorbidities and Bronchiectasis The Effect of Different Virtual Reality-Based Exercise Trainings on Pulmonary Function, Respiratory and Peripheral Muscle Strength, Functional Capacity and Balance in Children With Bronchiectasis Functional Respiratory Imaging in Bronchiectasis Safety and Potential Efficacy of Human Mesenchymal Stem Cells in Non‐Cystic Fibrosis Bronchiectasis Long-term Prognosis of Children With Bronchiectasis Treated With Low-dose Erythromycin Intervention Formoterol-beclomethasone in Patients With Bronchiectasis: a Randomized Controlled Trial Respiratory Mechanics Effects of Flutter Valve in Bronchiectasis Patients Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis Safety and Effectiveness of AZLI (an Inhaled Antibiotic) in Adults With Non-Cystic Fibrosis Bronchiectasis Feasibility Study of the AffloVest in Bronchiectasis Atorvastatin in Bronchiectasis in Patients With Pseudomonas Aeruginosa The Effect of Theophylline in the Treatment of Bronchiectasis Bronchiectasis and Long Term Azithromycin Treatment Clinimetric Properties of Outcome Measures in Bronchiectasis in the UK Ciprofloxacin Dry Powder for Inhalation (DPI) in Non-cystic Fibrosis Bronchiectasis (Non-CF BE) Pain Mechanisms in Patients With Bronchiectasis Efficacy of Roflumilast on Exacerbations in Patients With Non-cystic Fibrosis Bronchiectasis A Study to Access Safety and Efficacy of Nebulized Tobramycin in Patients With Bronchiectasis Bronchoalveolar Lavage for Bronchiectasis Patients With Exacerbation Efficacy of Azithromycin in Treatment of Bronchiectasis Airway Clearance in Bronchiectasis: is Non-Invasive Ventilation a Useful Adjunct in Moderate to Severe Disease? Effects of Azithromycin on Airway Oxidative Stress Markers in Patients With Bronchiectasis Efficacy of Budesonide-Formoterol in Bronchiectasis Exhaled Breath Condensate Assessment in Stable Non-Cystic Fibrotic Bronchiectasis Ciprofloxacin Dry Powder for Inhalation in Non-cystic Fibrosis Bronchiectasis (Non-CF BE) Long-term Airway Clearance Therapy in Non-cystic Fibrosis Bronchiectasis Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of QBW251 in Subjects With Bronchiectasis Mucus Solids Concentration in Patients With Bronchiectasis Target Validation and Discovery in Idiopathic Bronchiectasis Exercise Capacity in Bronchiectasis Resection Physical Activity in Bronchiectasis The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis Effect of AIRVO Heated Humidification in Bronchiectasis A Safety Trial of DAS181 (Fludase®) in Adult Subjects With Well-Controlled Asthma or Bronchiectasis A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis Salmeterol-Fluticasone Combined Inhaled Therapy for Non-cystic Fibrosis Bronchiectasis Lung Dispersing, Turbid Descending and Gut Clearing Decoction for Bronchiectasis Is Regular Chest Physiotherapy an Effective Treatment in Severe, Non Cystic Fibrosis Bronchiectasis? Pulmonary Rehabilitation Program (PRP) Versus PRP Plus Nutritional Supplementation in Patients With Bronchiectasis Autologous Transplantation of Bronchial Basal Cells for Treatment of Bronchiectasis Efficacy and Safety of Hydrogen Inhalation on Bronchiectasis: A Randomized, Multi-center, Double-blind Study Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Bronchiectasis Effects of High Intensity Inspiratory Muscle Training on Exercise Capacity in Patients With Bronchiectasis Reaction Time and Postural Control in Individuals With Cystic Fibrosis and Bronchiectasis Impact of Chronic Air Pollution on Non-cystic Fibrosis Bronchiectasis Comparison of Physical Activity Level Between Patients With Bronchiectasis and Healthy Subjects Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis Hypertonic Saline (6%) Versus Isotonic Saline (0.9%) in Bronchiectasis Evaluation of the Quality of Life Questionnaire-Bronchiectasis (QOL-B) in Patients With Bronchiectasis The Effect of Bronchiectasis on the Exacerbation and Mortality in COPD Inhaled A1AT in Adult Stable Bronchiectasis Prevention of Bronchiectasis in Infants With Cystic Fibrosis Pulmonary Rehabilitation in Non-Cystic Fibrosis Bronchiectasis Metabolomic Analysis of Exhaled Breath Condensates in Patients With COPD and Bronchiectasis Physical Capacity in Patients With Bronchiectasis Before and After Rehabilitation Program In-exsufflator Cough Assist Device in Patients With Symptomatic Bronchiectasis Bronchiectasis Effect in COPD Patients Prevalence and Characteristics of Patients With Bronchiectasis Comorbid Nontuberculous Mycobacteria Aetiology of Children With Bronchiectasis in China Macrolides in COPD- Bronchiectasis Overlap Value of Inhaled Treatment With Aztreonam Lysine in Bronchiectasis Pharmacokinetic Evaluation and Tolerability of Dry Powder Tobramycin by a Novel Device in Patients With Non Cystic Fibrosis Bronchiectasis Comparison of Sit-to-stand Test With Six-minute Walk Test in Bronchiectasis and Healthy Children Characterization of Airway Mucus in Bronchiectasis Patients and Healthy Controls The PROspective German NOn-CF bronchiectaSIS Patient Registry The BRIDGE Study – Bronchiectasis Research Involving Databases, Genomics and Endotyping Role of Innate Immunity in Non-Cystic Fibrosis Bronchiectasis Exercise Capacity in Patients With Cystic Fibrosis vs. Non-cystic Fibrosis Bronchiectasis Evaluation of Medical and Nursing Management for Bronchiectasis A Pilot Study to Evaluate the Use of the Vest® System for Treatment of Bronchiectasis Patients in the Home Setting The Establishment of China Bronchiectasis Registry and Research Collaboration Short-and Long-term Effects of a Home-based Rehabilitation Program in Patients With Bronchiectasis The Role of Viral Infection in Acute Exacerbations of Non-cystic Fibrosis Bronchiectasis in Adults Bronchiectasis: Evaluation of an Educational Intervention Prevalence of Bronchiectasis in COPD Patients ELTGOL and Bronchiectasis. Respiratory Therapy Bacteriology and Inflammation in Bronchiectasis Different Phenotypes of Bronchiectasis Effects of Traditional Chinese Medicine on Bronchiectasis Patients The Prevalence and Impact of Depression and Anxiety Symptoms in Patients With Non-CF Bronchiectasis

Brief Title

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

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

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.
    

Detailed Description

      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 study will consist of a screening period, a run-in and two dosing and evaluation periods
      (with a minimum two-day break in between) and a follow-up period.

      The dosing and evaluation period of the study is divided into two consecutive components:

        1. Dose escalation study

           - This segment of the treatment period is designed to assess the safety and tolerability
           of escalating doses of S-1226 (4%, 8% and 12%) in those with mild-moderate CF and non CF
           bronchiectasis

        2. Daily dosing study - This segment of the treatment period is designed to assess the
           short term (5 day) safety and tolerability of twice daily administration of a fixed dose
           of S-1226 in subjects with mild-moderate CF and non CF bronchiectasis.

      The primary aim of this study of S-1226 is to capture information to inform follow-up S-1226
      clinical studies in CF and non CF bronchiectasis. Important in this regard will be data on
      safety, tolerability, dosing and efficacy. Specifically, regarding efficacy, the
      investigators want to examine for optimal dose ranging and magnitude of the effect to
      determine the power calculations for any follow-up studies and to determine which outcome
      measures best reflect the effects of the drug. Because the study is investigational in
      nature, it will be un-blinded and information will be analyzed as it is collected.

      During the screening and the run-in period, the subjects will have safety assessments and all
      eligibility criteria confirmed. The run-in period involves meeting with the study subjects 1
      - 2 weeks prior to the start of the treatment for a physical exam, concomitant medication
      review, spirometry and information regarding the study. The consent process will also take
      place at this stage.

      The dose escalation period will include 3 days of twice daily treatment of the study drug
      with a washout period in between. The dose of CO2 in S-1226 will be sequentially escalated
      for the particular subject from the starting dose of 4% CO2. Planned subsequent dose levels
      are 8% and 12% CO2, although doses may be adjusted within this range based on safety and
      tolerability data from the completed dosing days. Subjects will not be dosed with a higher
      CO2 level until drug administration of the preceding dose level has been completed and safety
      data reviewed by the Safety Committee and a decision taken to proceed or not with the next
      sequential dose level.

      There will be a washout period between the dose escalation and the daily dosing study. The
      daily dosing study will include 5 days of twice daily treatment of the study drug based on
      the results of the dose escalation study. Lung function tests will be performed before and
      after the treatment.

      Subjects in the Home Extension Study will receive S-1226 twice daily for 28 consecutive days.
      Subjects will monitor daily symptom scores. Oxygen saturation values, as determined by pulse
      oximetry, will be monitored 2 minutes prior to therapy, during therapy and for up to 30
      minutes post therapy. Pulmonary function studies will be assessed weekly by the designated
      respiratory therapist between 4-7 pm.

      The follow-up phase will occur 10-14 days after completion of the final dose. This will
      involve a clinical exam, spirometry and completion of CFQ-R.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Treatment-emergent adverse events

Secondary Outcome

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

Condition

Cystic Fibrosis

Intervention

S-1226

Study Arms / Comparison Groups

 Dose Escalation Study
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

12

Start Date

August 8, 2019

Completion Date

August 2022

Primary Completion Date

February 2022

Eligibility 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.
      

Gender

All

Ages

14 Years - 50 Years

Accepts Healthy Volunteers

No

Contacts

Mark Montgomery, MD, 403-689-5989, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT03903913

Organization ID

SAMi-03-1-01


Responsible Party

Sponsor

Study Sponsor

SolAeroMed Inc.


Study Sponsor

Mark Montgomery, MD, Principal Investigator, University of Calgary


Verification Date

June 2021