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

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: CSJ117; Drug: Placebo Comparator

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Novartis Investigative Site
  • Saskatchewan, Canada, S7K 0M7
    • Novartis Investigative Site
  • Vancouver, Canada
    • Novartis Investigative Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T6G 2B7
      • Novartis Investigative Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Novartis Investigative Site
• Germany
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Grosshansdorf, Germany, 22927
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSJ117; low dose, medium dose, or high dose administered as a once daily inhaled dose	Drug: CSJ117; inhaled once daily dose
Placebo Comparator: Placebo; placebo comparator administered as once daily inhaled dose	Drug: Placebo Comparator; inhaled once daily dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CCSJ117X2201 from the Novartis Clinical Trials Website
• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): July 16, 2019
• Study Completion (Actual): July 16, 2019

Study Registration Dates

• First Submitted: May 1, 2017
• First Submitted That Met QC Criteria: May 1, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: tolerability; safety; asthma; pharmacokinetics; pharmacodynamics; allergen bronchoprovocation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CCSJ117X2201; 2016-004929-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No