CCSJ117A12201C

Novartis Pharma AG

Novartis Campus, Basel, Switzerland,

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

No

No

No

Final

06 Sep 2022

No

Yes

06 Sep 2022

Yes

The primary objective of the trial was to characterize the dose-response relationship of five doses of CSJ117 inhaled daily on lung function, compared with placebo, at the end of the 12-week active-treatment period.

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

09 Sep 2020

No

Yes

Philippines: 7

Russian Federation: 8

Belgium: 3

Bulgaria: 13

Czechia: 10

Germany: 50

Hungary: 17

Latvia: 14

Poland: 29

Slovakia: 2

Japan: 64

Argentina: 53

Canada: 6

Guatemala: 12

United States: 47

335

138

0

0

0

0

0

0

281

54

0

Overall Study (overall period)

Randomised - controlled

Yes

CSJ117

Inhalation powder, hard capsule

Inhalation use

Run-in period: Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period: CSJ117 0.5 mg inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

CSJ117

Inhalation powder, hard capsule

Inhalation use

Run-in period: Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period: CSJ117 1 mg inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

CSJ117

Inhalation powder, hard capsule

Inhalation use

Run-in period: Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period: CSJ117 2 mg inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

CSJ117

Inhalation powder, hard capsule

Inhalation use

Run-in period: Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period: CSJ117 4 mg inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

CSJ117

Inhalation powder, hard capsule

Inhalation use

Run-in period: Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period: CSJ117 8 mg inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

CSJ117

Inhalation powder, hard capsule

Inhalation use

Run-in period: Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period: Placebo inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

CSJ117 0.5mg

CSJ117 1mg

CSJ117 2mg

CSJ117 4mg

CSJ117 8mg

Placebo

CSJ117 0.5mg

CSJ117 1mg

CSJ117 2mg

CSJ117 4mg

CSJ117 8mg

Placebo

FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Pre-dose FEV1 is defined as average of the two FEV1 measurements taken at approximately 45 minutes and 15 minutes prior to dosing. The baseline pre-dose FEV1 value is defined as the average of the values taken approximately 2 hours 45 minutes and 2 hours 15 minutes prior to the first dose of double-blind treatment at Day 1. The least-squares means for change from baseline in pre-dose FEV1 averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM). A positive average change from baseline in pre-dose FEV1 is considered a favorable outcome.

Primary

Baseline, Weeks 8-12

Treatment difference (CSJ117-placebo)

CSJ117 1mg v Placebo

112

Pre-specified

0.058

2-sided

Standard error of the mean

0.0542

Treatment difference (CSJ117-placebo)

CSJ117 0.5mg v Placebo

111

Pre-specified

0.122

2-sided

Standard error of the mean

0.0541

Treatment difference (CSJ117-placebo)

CSJ117 4mg v Placebo

151

Pre-specified

0.009

2-sided

Standard error of the mean

0.043

Treatment difference (CSJ117-placebo)

CSJ117 8mg v Placebo

149

Pre-specified

-0.008

2-sided

Standard error of the mean

0.0434

Treatment difference (CSJ117-placebo)

CSJ117 2mg v Placebo

112

Pre-specified

0.065

2-sided

Standard error of the mean

0.0521

Fractional exhaled Nitric Oxide (FeNO) pre-dose measurements were done at the investigational sites prior to spirometry assessments. FeNO is defined as the mean of two serial measurements. The measurement of exhaled nitric oxide is widely accepted as a non-invasive marker of airway inflammation (inflammation leads to elevation of FeNO). The baseline FeNO pre-dose measurements were taken at the end of the run-in period. The least-squares means for change from baseline in FeNO averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM). A negative average change from baseline in FeNO is considered a favorable outcome.

Secondary

Baseline, Weeks 8-12

Treatment difference (CSJ117-placebo)

CSJ117 0.5mg v Placebo

111

Pre-specified

-1.568

2-sided

Standard error of the mean

2.363

Treatment difference (CSJ117-placebo)

CSJ117 1mg v Placebo

112

Pre-specified

-3.998

2-sided

Standard error of the mean

2.384

Treatment difference (CSJ117-placebo)

CSJ117 2mg v Placebo

112

Pre-specified

-2.889

2-sided

Standard error of the mean

2.2943

Treatment difference (CSJ117-placebo)

CSJ117 4mg v Placebo

151

Pre-specified

-0.287

2-sided

Standard error of the mean

1.8718

Treatment difference (CSJ117-placebo)

CSJ117 8mg v Placebo

149

Pre-specified

1.093

2-sided

Standard error of the mean

1.8652

PEF (Peak Expiratory Flow) is a person's maximum speed of expiration. All participants were instructed to record PEF twice daily before taking any medication using an electronic peak expiratory flow device (eDiary/ePEF), once in the morning and once approximately 12 hours later in the evening at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the eDiary/ePEF. Mean morning and evening PEF values were calculated by weekly intervals. The baseline values of PEF were the mean values in the run-in period. A positive change from baseline in PEF is considered a favorable outcome.

Secondary

Baseline, Week 12

PEF (Peak Expiratory Flow) is a person's maximum speed of expiration. All participants were instructed to record PEF twice daily before taking any medication using an electronic peak expiratory flow device (eDiary/ePEF), once in the morning and once approximately 12 hours later in the evening at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the eDiary/ePEF. Mean morning and evening PEF values were calculated by weekly intervals. The baseline values of PEF were the mean values in the run-in period. A positive change from baseline in PEF is considered a favorable outcome.

Secondary

Baseline, Week 12

The Asthma Control Questionnaire-5 (ACQ-5) is a five-item, self-completed questionnaire, which is used as a measure of asthma symptom control. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the overall ACQ-5 score is the mean of all 5 questions, therefore between 0 (totally controlled) and 6 (severely uncontrolled). The baseline values of ACQ-5 were collected at the end of the run-in period. The least-squares means for change from baseline in ACQ-5 score averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM). A negative change from baseline in ACQ-5 is considered a favorable outcome.

Secondary

Baseline, Weeks 8-12

Treatment difference (CSJ117-placebo)

CSJ117 0.5mg v Placebo

111

Pre-specified

-0.042

2-sided

Standard error of the mean

0.1493

Treatment difference (CSJ117-placebo)

CSJ117 1mg v Placebo

112

Pre-specified

-0.42

2-sided

Standard error of the mean

0.1489

Treatment difference (CSJ117-placebo)

CSJ117 8mg v Placebo

149

Pre-specified

-0.115

2-sided

Standard error of the mean

0.1184

Treatment difference (CSJ117-placebo)

CSJ117 4mg v Placebo

151

Pre-specified

-0.017

2-sided

Standard error of the mean

0.1182

Treatment difference (CSJ117-placebo)

CSJ117 2mg v Placebo

112

Pre-specified

-0.289

2-sided

Standard error of the mean

0.1446

The Asthma Quality of Life Questionnaire+12 (AQLQ+12) is a disease specific questionnaire, which is used as a measure of health-related quality of life. The AQLQ+12 comprises a total of 32 individual questions that span a total of 4 domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The overall AQLQ+12 score is the mean of all 32 individual responses, therefore between 7 and 1 with higher scores indicating less impairment in health-related quality of life. The baseline values of AQLQ+12 were collected at the end of the run-in period. The least-squares means for change from baseline in AQLQ+12 score averaged between Week 8 and Week 12 visits were obtained from a linear mixed effects model for repeated measures (MMRM). A positive change from baseline is considered a favorable outcome.

Secondary

Baseline, Weeks 8-12

Treatment difference (CSJ117-placebo)

CSJ117 0.5mg v Placebo

111

Pre-specified

-0.097

2-sided

Standard error of the mean

0.1485

Treatment difference (CSJ117-placebo)

CSJ117 1mg v Placebo

112

Pre-specified

0.218

2-sided

Standard error of the mean

0.1484

Treatment difference (CSJ117-placebo)

CSJ117 4mg v Placebo

151

Pre-specified

0.033

2-sided

Standard error of the mean

0.118

Treatment difference (CSJ117-placebo)

CSJ117 8mg v Placebo

149

Pre-specified

0.073

2-sided

Standard error of the mean

0.118

Treatment difference (CSJ117-placebo)

CSJ117 2mg v Placebo

112

Pre-specified

0.078

2-sided

Standard error of the mean

0.145

Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) are patient reported outcome measures of asthma symptom severity. Patients recorded asthma symptoms twice daily in the eDiary. Severity of daytime asthma symptoms were assessed before going to bed and severity of nighttime symptoms upon waking. Both diaries comprised of 6 items assessing breathing symptoms (difficulty breathing, wheezing, and shortness of breath), chest symptoms (chest tightness and chest pain), and cough symptoms (cough). All items were assessed using an 11-point numeric rating scale ranging from 0 (‘None’) to 10 (‘As bad as you can imagine’). The overall score is the mean of all 6 individual responses, therefore between 0 and 10 with higher scores indicating more severe symptoms. Mean daily scores of both diaries were calculated by weekly intervals. The baseline values were defined as the average score during the run-in period. A negative change from baseline is a favorable outcome.

Secondary

Baseline, Week 8 and Week 12

Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) are patient reported outcome measures of asthma symptom severity. Patients recorded asthma symptoms twice daily in the eDiary. Severity of daytime asthma symptoms were assessed before going to bed and severity of nighttime symptoms upon waking. Both diaries comprised of 6 items assessing breathing symptoms (difficulty breathing, wheezing, and shortness of breath), chest symptoms (chest tightness and chest pain), and cough symptoms (cough). All items were assessed using an 11-point numeric rating scale ranging from 0 (‘None’) to 10 (‘As bad as you can imagine’). The overall score is the mean of all 6 individual responses, therefore between 0 and 10 with higher scores indicating more severe symptoms. Mean daily scores of both diaries were calculated by weekly intervals. The baseline values were defined as the average score during the run-in period. A negative change from baseline is a favorable outcome.

Secondary

Baseline, Week 8 and Week 12

Participants were given a short acting β2-agonist (SABA) such as salbutamol (100 µg) or albuterol (90 µg) to use as rescue medication throughout the study. Participants recorded in the eDiary, once in the morning and once in the evening, the use of rescue medication (number of puffs of SABA taken in the previous 12 hours). The total number of puffs of SABA taken per day was calculated and the mean daily use of puffs of SABA was derived by weekly intervals. The baseline value of number of puffs of SABA taken per day is the average of total daily SABA use during the run-in period. A negative change from baseline is considered a favorable outcome.

Secondary

Baseline, Week 12

Number of participants with AEs and SAEs, including asthma exacerbations, changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs during the on-treatment period. The on-treatment period is between the date of first dose of double-blind study treatment and date of the last dose of randomized study treatment. Grades to characterize the severity of the adverse events were based on the Common Terminology Criteria for Adverse Events (CTCAE). For CTCAE, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. The number of participants in each category is reported in the table.

Secondary

From first dose of double-blind study treatment up to last dose (Week 12)

Immunogenicity (antibody formation against CSJ117) was evaluated in serum by a validated bridging electrochemiluminescence immunoassay (ECLIA).

Secondary

Day 1 and Weeks 2, 4, 8, 12, 14, 16, 20 and 24

CSJ117 concentration was determined in serum by a validated immunoassay method. Concentrations below the lower limit of quantification (LLOQ) were treated as “zero”.

Secondary

Day 1 and Week 12: pre-dose, 2 and 4 hours post-dose; Weeks 2, 4 and 8: pre-dose and 4 hours post-dose; Weeks 14, 16, 20 and 24: pre-dose

From first dose of double-blind study treatment up to 12 weeks after last dose (Week 24)

25.0

CSJ117 8mg

CSJ117 4mg

CSJ117 2mg

CSJ117 1mg

CSJ117 0.5mg

Placebo