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

Phase 1

Completed

• Conditions: Asthma
• Interventions: Drug: CSJ117; Drug: Placebo Comparator

• Registration Number: NCT03138811
• Lead Sponsor: Novartis Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-01
• Study First Submitted QC: 2017-05-01
• Study First Posted: 2017-05-03
• Study Start: 2017-12-18
• Primary Completion: 2019-07-16
• Study Completion: 2019-07-16
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-07
• Last Update Posted: 2021-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CSJ117	CSJ117	low dose, medium dose, or high dose administered as a once daily inhaled dose
Placebo	Placebo Comparator	placebo comparator administered as once daily inhaled dose

Primary Outcome Measures

Name	Time	Method
Number of adverse events and serious adverse events	12 weeks	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	12 weeks	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	12 weeks	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

Name	Time	Method
Late asthmatic response as measured by the minimum absolute FEV1	6 weeks and 12 weeks	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	12 weeks	Tmax is the time to reach the maximum concentration after drug administration
Measurement of CSJ117 serum concentration and calculation of Cmax	12 weeks	Cmax is the observed maximum plasma concentration following drug administration
Early asthmatic response as measured by the time adjusted AUC percent decrease in FEV1	6 weeks and 12 weeks	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.
Measurement of CSJ117 serum concentration and calculation of Lambda_z	12 weeks	Lambda_z is the apparent elimination rate constant
Measurement of CSJ117 serum concentration and calculation of T1/2	12 weeks	T1/2 is the terminal elimination half-life \[time\]
Early asthmatic response as measured by the maximum percentage decrease in FEV1	6 weeks and 12 weeks	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.
Late asthmatic response as measured by the maximum percentage decrease in FEV1	6 weeks	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.
Measurement of CSJ117 serum concentration and calculation of AUCtau	12 weeks	The area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau \[mass x time / volume\]
Early asthmatic response as measured by the minimum of the absolute in FEV1	6 weeks and 12 weeks	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	6 weeks	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.
Measurement of CSJ117 serum concentration and calculation of Ctrough)	12 weeks	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	12 weeks	Racc is the accumulation ratio

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Mainz, Germany