Back to resultsA Bronchoprovocation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CSJ117 in Adult Subjects With Mild Atopic Asthma
Primary Purpose
Asthma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CSJ117
Placebo Comparator
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring asthma, allergen bronchoprovocation, pharmacodynamics, pharmacokinetics, safety, tolerability
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CSJ117
Placebo
Arm Description
low dose, medium dose, or high dose administered as a once daily inhaled dose
placebo comparator administered as once daily inhaled dose
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Measurement of CSJ117 serum concentration and calculation of Tmax
Tmax is the time to reach the maximum concentration after drug administration
Measurement of CSJ117 serum concentration and calculation of Cmax
Cmax is the observed maximum plasma concentration following drug administration
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]
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.
Measurement of CSJ117 serum concentration and calculation of Racc
Racc is the accumulation ratio
Measurement of CSJ117 serum concentration and calculation of Lambda_z
Lambda_z is the apparent elimination rate constant
Measurement of CSJ117 serum concentration and calculation of T1/2
T1/2 is the terminal elimination half-life [time]
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03138811
Brief Title
A Bronchoprovocation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CSJ117 in Adult Subjects With Mild Atopic Asthma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
December 18, 2017 (Actual)
Primary Completion Date
July 16, 2019 (Actual)
Study Completion Date
July 16, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
asthma, allergen bronchoprovocation, pharmacodynamics, pharmacokinetics, safety, tolerability
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSJ117
Arm Type
Experimental
Arm Description
low dose, medium dose, or high dose administered as a once daily inhaled dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo comparator administered as once daily inhaled dose
Intervention Type
Drug
Intervention Name(s)
CSJ117
Intervention Description
inhaled once daily dose
Intervention Type
Drug
Intervention Name(s)
Placebo Comparator
Intervention Description
inhaled once daily dose
Primary Outcome Measure Information:
Title
Number of adverse events and serious adverse events
Description
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.
Time Frame
12 weeks
Title
Late asthmatic response as measured by the AUC for time adjusted percent decrease in FEV1
Description
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.
Time Frame
12 weeks
Title
Late asthmatic response as measured by the maximum percentage decrease in FEV1
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Early asthmatic response as measured by the time adjusted AUC percent decrease in FEV1
Description
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.
Time Frame
6 weeks and 12 weeks
Title
Early asthmatic response as measured by the maximum percentage decrease in FEV1
Description
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.
Time Frame
6 weeks and 12 weeks
Title
Early asthmatic response as measured by the minimum of the absolute in FEV1
Description
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.
Time Frame
6 weeks and 12 weeks
Title
Late asthmatic response as measured by the time adjusted AUC in FEV1
Description
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.
Time Frame
6 weeks
Title
Late asthmatic response as measured by the maximum percentage decrease in FEV1
Description
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.
Time Frame
6 weeks
Title
Late asthmatic response as measured by the minimum absolute FEV1
Description
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.
Time Frame
6 weeks and 12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of Tmax
Description
Tmax is the time to reach the maximum concentration after drug administration
Time Frame
12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of Cmax
Description
Cmax is the observed maximum plasma concentration following drug administration
Time Frame
12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of AUCtau
Description
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]
Time Frame
12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of Ctrough)
Description
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.
Time Frame
12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of Racc
Description
Racc is the accumulation ratio
Time Frame
12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of Lambda_z
Description
Lambda_z is the apparent elimination rate constant
Time Frame
12 weeks
Title
Measurement of CSJ117 serum concentration and calculation of T1/2
Description
T1/2 is the terminal elimination half-life [time]
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Novartis Investigative Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Novartis Investigative Site
City
Saskatchewan
ZIP/Postal Code
S7K 0M7
Country
Canada
Facility Name
Novartis Investigative Site
City
Vancouver
Country
Canada
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Novartis Investigative Site
City
Grosshansdorf
ZIP/Postal Code
22927
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17681
Description
Results for CCSJ117X2201 from the Novartis Clinical Trials Website
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=609
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com
Learn more about this trial
A Bronchoprovocation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CSJ117 in Adult Subjects With Mild Atopic Asthma
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