A Bronchoprovocation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CSJ117 in Adult Subjects With Mild Atopic Asthma

Study Overview
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Brief Summary
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This is a non-confirmatory, randomized, subject and investigator blinded, placebo-controlled, parallel-design, multi-center bronchoprovocation study. Approximately 55 subjects with mild stable atopic asthma who exhibit an EAR and LAR to a common inhaled allergen will receive multiple once daily doses of inhaled CSJ117 or placebo over 12 weeks. Two sequential dose cohorts are planned for this study, Cohort 1 and Cohort 2. Cohort 2 will be split into two parts, Cohort 2a and 2b

Official Title
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A Randomized, Subject- and Investigator-blinded, Placebo-controlled, Paralleldesign, Bronchoprovocation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of Inhaled CSJ117 in Adult Subjects With Mild Atopic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: CSJ117
* Drug: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of stable mild atopic asthma, as defined by the American Thoracic Society/ European Respiratory Society statement, who exhibit an early and late asthmatic response to a common inhaled allergen during the screening allergen inhalation challenge. Throughout the screening period and at baseline, only infrequent use of inhaled short-acting beta2-agonists (less than or equal to twice weekly) to treat asthma and/or prophylactic use prior to exercise. Inhaled short-acting beta2-agonist must be withheld for 8 hours before spirometry. Exclusion Criteria: Hospitalization or emergency room treatment for acute asthma in the 6 months prior to screening or during the screening period. Any worsening or exacerbation of asthma (e.g., an event requiring a change in treatment) in the six weeks before screening or during the screening period. A history of any clinically significant chronic pulmonary disease other than mild atopic asthma, including but not limited to COPD, interstitial lung disease or bronchiectasis Use of immunosuppressive medications or allergen-specific immunotherapy within 6 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSJ117<br>low dose, medium dose, or high dose administered as a once daily inhaled dose | Drug: CSJ117<br>* inhaled once daily dose<br>|
| Placebo Comparator: Placebo<br>placebo comparator administered as once daily inhaled dose | Drug: Placebo Comparator<br>* inhaled once daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events and serious adverse events | An AE is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. Study drug includes the investigational drug under evaluation and the comparator drug or placebo that is given during any phase of the study. Adverse events starting on or after the time of the first inhalation of study drug are classified as a treatment emergent adverse event. | 12 weeks | 
| Late asthmatic response as measured by the AUC for time adjusted percent decrease in FEV1 | Late asthmatic response (LAR) is considered a ≥ 15% fall in FEV1 between 3 and 7 hours after an allergen inhalation challenge. The AUC for time adjusted percent decrease in FEV1 will be compared between CSJ117 and placebo groups. | 12 weeks | 
| Late asthmatic response as measured by the maximum percentage decrease in FEV1 | Late asthmatic response (LAR) is considered a ≥ 15% fall in FEV1 between 3 and 7 hours after an allergen inhalation challenge. The maximum percentage decrease in FEV1 will be compared between CSJ117 and placebo groups. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early asthmatic response as measured by the time adjusted AUC percent decrease in FEV1 | Early asthmatic response (EAR) is considered a ≥ 20% fall in FEV1 within the 2 hours after an allergen inhalation challenge. The time adjusted AUC percent decrease will be compared between CSJ117 and placebo groups. | 6 weeks and 12 weeks | 
| Early asthmatic response as measured by the maximum percentage decrease in FEV1 | Early asthmatic response (EAR) is considered a ≥ 20% fall in FEV1 within the 2 hours after an allergen inhalation challenge. The maximum percentage decrease will be compared between CSJ117 and placebo groups. | 6 weeks and 12 weeks | 
| Early asthmatic response as measured by the minimum of the absolute in FEV1 | Early asthmatic response (EAR) is considered a ≥ 20% fall in FEV1 within the 2 hours after an allergen inhalation challenge. The minimum of the absolute in FEV1 will be compared between CSJ117 and placebo groups. | 6 weeks and 12 weeks | 
| Late asthmatic response as measured by the time adjusted AUC in FEV1 | Late asthmatic response (LAR) is considered a ≥ 15% fall in FEV1 between 3 and 7 hours after an allergen inhalation challenge. The time adjusted in FEV1 will be compared between CSJ117 and placebo groups. | 6 weeks | 
| Late asthmatic response as measured by the maximum percentage decrease in FEV1 | Late asthmatic response (LAR) is considered a ≥ 15% fall in FEV1 between 3 and 7 hours after an allergen inhalation challenge. The maximum percentage decrease in FEV1 will be compared between CSJ117 and placebo groups. | 6 weeks | 
| Late asthmatic response as measured by the minimum absolute FEV1 | Late asthmatic response (LAR) is considered a ≥ 15% fall in FEV1 between 3 and 7 hours after an allergen inhalation challenge. The minimum absolute in FEV1 will be compared between CSJ117 and placebo groups. | 6 weeks and 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of Tmax | Tmax is the time to reach the maximum concentration after drug administration | 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of Cmax | Cmax is the observed maximum plasma concentration following drug administration | 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of AUCtau | The area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau [mass x time / volume] | 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of Ctrough) | Ctrough is the observed serum (or plasma or blood) concentration that is just prior to the beginning of, or at the end of, a dosing interval. | 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of Racc | Racc is the accumulation ratio | 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of Lambda_z | Lambda_z is the apparent elimination rate constant | 12 weeks | 
| Measurement of CSJ117 serum concentration and calculation of T1/2 | T1/2 is the terminal elimination half-life [time] | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, allergen bronchoprovocation, pharmacodynamics, pharmacokinetics, safety, tolerability