Asthma
Conditions
Keywords
CSJ117, uncontrolled asthma
Brief summary
The purpose of this study is to determine the efficacy and safety of multiple CSJ117 doses (0.5; 1; 2; 4 and 8 mg) inhaled once daily compared with placebo, when added to standard-of-care (SoC) asthma therapy in adult patients with uncontrolled asthma with respect to change from baseline in FEV1 at the end of 12 weeks of treatment.
Detailed description
This was a randomized, multicenter, multi-national, double-blind, placebo-controlled, parallel-arm study evaluating the effect of 5 dose levels of CSJ117 in adult subjects with inadequately controlled asthma despite medium to high dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA). Subjects were assigned to one of the following six treatment arms/groups in a ratio of 2:1:1:1:2:2: * Placebo inhaled once daily * CSJ117 0.5 mg inhaled once daily * CSJ117 1.0 mg inhaled once daily * CSJ117 2.0 mg inhaled once daily * CSJ117 4.0 mg inhaled once daily * CSJ117 8.0 mg inhaled once daily The study included: * A screening period of approximately 2 weeks * A single blinded placebo run-in period of 4 weeks (extended to 8 weeks for subjects experiencing an asthma exacerbation or respiratory tract infection during the run-in period) * A double blinded treatment period of 12 weeks * A follow-up period of up to 12 weeks, study drug free, following the last dose of study treatment. Patients who successfully completed 12 weeks of treatment in this study could be offered participation in the Safety Extension Study CCSJ117A12201E1 (NCT04946318).
Interventions
DRUGCSJ117
CSJ117 inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device. CSJ117 = inhaled monoclonal antibody fragment
DRUGPlacebo
Run-in period (all arms): 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 arm only): Placebo inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed asthma * Male and female patients aged ≥18 and ≤75 years * Patients who have been treated with medium or high dose ICS plus LABA with up to 2 additional controllers * Morning pre-BD FEV1 value of ≥ 40% and ≤ 85% of the predicted normal * A positive reversibility test * ACQ-5 score of ≥ 1.5 at screening and end of run-in visits.
Exclusion criteria
* Patients who have a cigarette smoking history of greater than 10 pack years or current smokers * Pregnant or nursing (lactating) women * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using specified methods of contraception during dosing of study drug and until 12 weeks after last study drug treatment * Patients with a history of immunodeficiency disease or hepatitis B, untreated and not cured hepatitis C or HIV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | Baseline, Weeks 8-12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in FeNO at Week 8 and Week 12 | Baseline, Weeks 8-12 | 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. |
| Change From Baseline in Morning PEF at Week 12 | 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. |
| Change From Baseline in Evening PEF at Week 12 | 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. |
| Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | Baseline, Weeks 8-12 | 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. |
| Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | Baseline, Weeks 8-12 | 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. |
| Change From Baseline in ADSD Score at Week 8 and Week 12 | 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. |
| Change From Baseline in ANSD Score at Week 8 and Week 12 | 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. |
| Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | Baseline, 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. |
| Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | From first dose of double-blind study treatment up to last dose (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. |
| Number of Participants With Anti-CSJ117 Antibodies | Day 1 and Weeks 2, 4, 8, 12, 14, 16, 20 and 24 | Immunogenicity (antibody formation against CSJ117) was evaluated in serum by a validated bridging electrochemiluminescence immunoassay (ECLIA). |
| CSJ117 Serum Concentration | 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 | CSJ117 concentration was determined in serum by a validated immunoassay method. Concentrations below the lower limit of quantification (LLOQ) were treated as zero. |
Countries
Argentina, Belgium, Bulgaria, Canada, Czechia, Germany, Guatemala, Hungary, Japan, Latvia, Philippines, Poland, Russia, Slovakia, United States
Participant flow
Recruitment details
Participants took part in 116 investigative sites in 15 countries.
Pre-assignment details
The screening period of approximately 2 weeks began after the participants had provided written informed consent. There was a single blinded placebo run-in period of 4 weeks (extended to 8 weeks for subjects experiencing an asthma exacerbation or respiratory tract infection during the run-in period) before starting the double blinded treatment period.
Participants by arm
| Arm | Count |
|---|---|
| CSJ117 0.5mg CSJ117 0.5 mg inhaled once daily | 36 |
| CSJ117 1mg CSJ117 1 mg inhaled once daily | 37 |
| CSJ117 2mg CSJ117 2 mg inhaled once daily | 37 |
| CSJ117 4mg CSJ117 4 mg inhaled once daily | 76 |
| CSJ117 8mg CSJ117 8 mg inhaled once daily | 74 |
| Placebo Placebo inhaled once daily | 75 |
| Total | 335 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol deviation | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Study terminated by sponsor | 1 | 3 | 2 | 6 | 3 | 4 |
| Overall Study | Subject decision | 2 | 0 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | CSJ117 0.5mg | CSJ117 1mg | CSJ117 2mg | CSJ117 4mg | CSJ117 8mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 12.89 | 51.2 years STANDARD_DEVIATION 12.09 | 51.4 years STANDARD_DEVIATION 13.31 | 50.3 years STANDARD_DEVIATION 12.8 | 52.7 years STANDARD_DEVIATION 12.22 | 51.5 years STANDARD_DEVIATION 13.46 | 51.3 years STANDARD_DEVIATION 12.76 |
| Age, Customized 18 - <40 years | 9 Participants | 6 Participants | 8 Participants | 16 Participants | 10 Participants | 19 Participants | 68 Participants |
| Age, Customized 40 - <65 years | 23 Participants | 26 Participants | 23 Participants | 50 Participants | 50 Participants | 41 Participants | 213 Participants |
| Age, Customized ≥65 years | 4 Participants | 5 Participants | 6 Participants | 10 Participants | 14 Participants | 15 Participants | 54 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 8 Participants | 7 Participants | 17 Participants | 16 Participants | 17 Participants | 73 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 5 Participants | 2 Participants | 10 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 26 Participants | 30 Participants | 56 Participants | 52 Participants | 53 Participants | 243 Participants |
| Sex: Female, Male Female | 27 Participants | 25 Participants | 21 Participants | 43 Participants | 48 Participants | 45 Participants | 209 Participants |
| Sex: Female, Male Male | 9 Participants | 12 Participants | 16 Participants | 33 Participants | 26 Participants | 30 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 37 | 0 / 37 | 0 / 76 | 0 / 74 | 0 / 75 |
| other Total, other adverse events | 12 / 36 | 14 / 37 | 20 / 37 | 31 / 76 | 23 / 74 | 27 / 75 |
| serious Total, serious adverse events | 1 / 36 | 0 / 37 | 0 / 37 | 1 / 76 | 0 / 74 | 1 / 75 |
Outcome results
Primary
Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12
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.
Time frame: Baseline, Weeks 8-12
Population: Full Analysis Set (FAS). The FAS included all participants to whom double-blind treatment had been assigned and who received at least one dose of double-blind treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | 0.173 liters (L) | Standard Error 0.0445 |
| CSJ117 1mg | Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | 0.109 liters (L) | Standard Error 0.0446 |
| CSJ117 2mg | Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | 0.116 liters (L) | Standard Error 0.0419 |
| CSJ117 4mg | Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | 0.060 liters (L) | Standard Error 0.0299 |
| CSJ117 8mg | Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | 0.043 liters (L) | Standard Error 0.0305 |
| Placebo | Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12 | 0.051 liters (L) | Standard Error 0.0309 |
p-value: 0.02595% CI: [0.016, 0.229]MMRM
p-value: 0.28695% CI: [-0.049, 0.165]MMRM
p-value: 0.21295% CI: [-0.037, 0.168]MMRM
p-value: 0.83195% CI: [-0.076, 0.094]MMRM
p-value: 0.85295% CI: [-0.094, 0.077]MMRM
Secondary
Average Change From Baseline in ACQ-5 Score at Week 8 and 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.
Time frame: Baseline, Weeks 8-12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | -0.764 score on a scale | Standard Error 0.123 |
| CSJ117 1mg | Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | -1.142 score on a scale | Standard Error 0.1225 |
| CSJ117 2mg | Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | -1.011 score on a scale | Standard Error 0.1171 |
| CSJ117 4mg | Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | -0.739 score on a scale | Standard Error 0.0824 |
| CSJ117 8mg | Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | -0.837 score on a scale | Standard Error 0.0829 |
| Placebo | Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12 | -0.722 score on a scale | Standard Error 0.0846 |
p-value: 0.88795% CI: [-0.249, 0.216]MMRM
p-value: 0.7895% CI: [-0.336, 0.252]MMRM
p-value: 0.00595% CI: [-0.713, -0.127]MMRM
p-value: 0.04795% CI: [-0.573, 0.004]MMRM
p-value: 0.33395% CI: [-0.348, 0.118]MMRM
Secondary
Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12
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.
Time frame: Baseline, Weeks 8-12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | 0.467 score on a scale | Standard Error 0.1223 |
| CSJ117 1mg | Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | 0.781 score on a scale | Standard Error 0.122 |
| CSJ117 2mg | Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | 0.642 score on a scale | Standard Error 0.1177 |
| CSJ117 4mg | Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | 0.597 score on a scale | Standard Error 0.0828 |
| CSJ117 8mg | Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | 0.636 score on a scale | Standard Error 0.0826 |
| Placebo | Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12 | 0.564 score on a scale | Standard Error 0.0842 |
p-value: 0.51595% CI: [-0.389, 0.195]MMRM
p-value: 0.14395% CI: [-0.074, 0.51]MMRM
p-value: 0.5995% CI: [-0.207, 0.364]MMRM
p-value: 0.77895% CI: [-0.199, 0.265]MMRM
p-value: 0.53995% CI: [-0.16, 0.305]MMRM
Secondary
Average Change From Baseline in FeNO at Week 8 and Week 12
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.
Time frame: Baseline, Weeks 8-12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Average Change From Baseline in FeNO at Week 8 and Week 12 | -2.869 parts per billion (ppb) | Standard Error 1.967 |
| CSJ117 1mg | Average Change From Baseline in FeNO at Week 8 and Week 12 | -5.299 parts per billion (ppb) | Standard Error 1.9872 |
| CSJ117 2mg | Average Change From Baseline in FeNO at Week 8 and Week 12 | -4.190 parts per billion (ppb) | Standard Error 1.876 |
| CSJ117 4mg | Average Change From Baseline in FeNO at Week 8 and Week 12 | -1.587 parts per billion (ppb) | Standard Error 1.3312 |
| CSJ117 8mg | Average Change From Baseline in FeNO at Week 8 and Week 12 | -0.208 parts per billion (ppb) | Standard Error 1.3248 |
| Placebo | Average Change From Baseline in FeNO at Week 8 and Week 12 | -1.301 parts per billion (ppb) | Standard Error 1.3142 |
p-value: 0.50895% CI: [-6.219, 3.083]MMRM
p-value: 0.09595% CI: [-8.691, 0.695]MMRM
p-value: 0.20995% CI: [-7.405, 1.627]MMRM
p-value: 0.87895% CI: [-3.971, 3.398]MMRM
p-value: 0.55895% CI: [-2.578, 4.765]MMRM
Secondary
Change From Baseline in ADSD Score at 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.
Time frame: Baseline, Week 8 and Week 12
Population: Participants in the Full Analysis Set with a valid measurement for the outcome measure at each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSJ117 0.5mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 8 | -0.24 score on a scale | Standard Deviation 0.678 |
| CSJ117 0.5mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 12 | -0.29 score on a scale | Standard Deviation 0.752 |
| CSJ117 1mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 8 | -0.42 score on a scale | Standard Deviation 0.622 |
| CSJ117 1mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 12 | -0.59 score on a scale | Standard Deviation 0.938 |
| CSJ117 2mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 8 | -0.35 score on a scale | Standard Deviation 0.773 |
| CSJ117 2mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 12 | -0.38 score on a scale | Standard Deviation 0.687 |
| CSJ117 4mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 8 | -0.32 score on a scale | Standard Deviation 0.555 |
| CSJ117 4mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 12 | -0.33 score on a scale | Standard Deviation 0.581 |
| CSJ117 8mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 8 | -0.33 score on a scale | Standard Deviation 0.787 |
| CSJ117 8mg | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 12 | -0.35 score on a scale | Standard Deviation 0.82 |
| Placebo | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 8 | -0.25 score on a scale | Standard Deviation 0.58 |
| Placebo | Change From Baseline in ADSD Score at Week 8 and Week 12 | Week 12 | -0.37 score on a scale | Standard Deviation 0.754 |
Secondary
Change From Baseline in ANSD Score at 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.
Time frame: Baseline, Week 8 and Week 12
Population: Participants in the Full Analysis Set with a valid measurement for the outcome measure at each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSJ117 0.5mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 8 | -0.15 score on a scale | Standard Deviation 0.637 |
| CSJ117 0.5mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 12 | -0.19 score on a scale | Standard Deviation 0.48 |
| CSJ117 1mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 8 | -0.35 score on a scale | Standard Deviation 0.629 |
| CSJ117 1mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 12 | -0.46 score on a scale | Standard Deviation 0.868 |
| CSJ117 2mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 8 | -0.30 score on a scale | Standard Deviation 0.76 |
| CSJ117 2mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 12 | -0.29 score on a scale | Standard Deviation 0.695 |
| CSJ117 4mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 8 | -0.27 score on a scale | Standard Deviation 0.547 |
| CSJ117 4mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 12 | -0.26 score on a scale | Standard Deviation 0.59 |
| CSJ117 8mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 8 | -0.26 score on a scale | Standard Deviation 0.753 |
| CSJ117 8mg | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 12 | -0.23 score on a scale | Standard Deviation 0.769 |
| Placebo | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 8 | -0.25 score on a scale | Standard Deviation 0.634 |
| Placebo | Change From Baseline in ANSD Score at Week 8 and Week 12 | Week 12 | -0.33 score on a scale | Standard Deviation 0.729 |
Secondary
Change From Baseline in Evening PEF at 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.
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set with a valid measurement for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Change From Baseline in Evening PEF at Week 12 | -5.3894 liters/minute | Standard Deviation 29.13968 |
| CSJ117 1mg | Change From Baseline in Evening PEF at Week 12 | -7.8709 liters/minute | Standard Deviation 29.06055 |
| CSJ117 2mg | Change From Baseline in Evening PEF at Week 12 | 14.0265 liters/minute | Standard Deviation 44.90062 |
| CSJ117 4mg | Change From Baseline in Evening PEF at Week 12 | 0.3893 liters/minute | Standard Deviation 30.47064 |
| CSJ117 8mg | Change From Baseline in Evening PEF at Week 12 | 2.6905 liters/minute | Standard Deviation 32.2786 |
| Placebo | Change From Baseline in Evening PEF at Week 12 | -3.2785 liters/minute | Standard Deviation 22.93816 |
Secondary
Change From Baseline in Morning PEF at 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.
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set with a valid measurement for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Change From Baseline in Morning PEF at Week 12 | -0.9785 liters/minute | Standard Deviation 22.73169 |
| CSJ117 1mg | Change From Baseline in Morning PEF at Week 12 | -1.7035 liters/minute | Standard Deviation 28.83957 |
| CSJ117 2mg | Change From Baseline in Morning PEF at Week 12 | 18.9496 liters/minute | Standard Deviation 50.09045 |
| CSJ117 4mg | Change From Baseline in Morning PEF at Week 12 | -0.0319 liters/minute | Standard Deviation 33.56218 |
| CSJ117 8mg | Change From Baseline in Morning PEF at Week 12 | 3.5702 liters/minute | Standard Deviation 37.05293 |
| Placebo | Change From Baseline in Morning PEF at Week 12 | -2.2060 liters/minute | Standard Deviation 24.56187 |
Secondary
Change From Baseline in Number of Puffs of SABA Taken Per Day at 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.
Time frame: Baseline, Week 12
Population: Participants in the Full Analysis Set with a valid measurement for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSJ117 0.5mg | Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | -0.2189 puffs of SABA per day | Standard Deviation 0.7234 |
| CSJ117 1mg | Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | -0.4548 puffs of SABA per day | Standard Deviation 0.88125 |
| CSJ117 2mg | Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | -0.3420 puffs of SABA per day | Standard Deviation 0.68267 |
| CSJ117 4mg | Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | -0.4310 puffs of SABA per day | Standard Deviation 0.80279 |
| CSJ117 8mg | Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | -0.3766 puffs of SABA per day | Standard Deviation 0.9807 |
| Placebo | Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12 | -0.3543 puffs of SABA per day | Standard Deviation 0.7842 |
Secondary
CSJ117 Serum Concentration
CSJ117 concentration was determined in serum by a validated immunoassay method. Concentrations below the lower limit of quantification (LLOQ) were treated as zero.
Time frame: 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
Population: Participants in the PK set with a valid measurement for the outcome measure. PK set is defined as participants with at least one evaluable drug concentration data sample. The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 4, 2 hours post-dose | 0.467 ng/mL | Standard Deviation 2.68 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 24, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 8, pre-dose | 1.69 ng/mL | Standard Deviation 4.34 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Day 1, 4 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Day 1, 2 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 16, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 8, 2 hours post-dose | 1.84 ng/mL | Standard Deviation 4.69 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 12, pre-dose | 1.83 ng/mL | Standard Deviation 4.69 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 2, pre-dose | 0.320 ng/mL | Standard Deviation 1.89 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 12, 2 hours post-dose | 2.02 ng/mL | Standard Deviation 4.68 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 14, pre-dose | 0.239 ng/mL | Standard Deviation 1.19 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 2, 2 hours post-dose | 0.389 ng/mL | Standard Deviation 2.3 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 12, 4 hours post-dose | 2.11 ng/mL | Standard Deviation 4.84 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 20, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Week 4, pre-dose | 0.336 ng/mL | Standard Deviation 1.93 |
| CSJ117 0.5mg | CSJ117 Serum Concentration | Day 1, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 12, 4 hours post-dose | 2.51 ng/mL | Standard Deviation 4.79 |
| CSJ117 1mg | CSJ117 Serum Concentration | Day 1, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 24, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 16, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 4, 2 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 8, pre-dose | 3.15 ng/mL | Standard Deviation 6.5 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 2, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 20, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 4, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 2, 2 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 8, 2 hours post-dose | 3.29 ng/mL | Standard Deviation 6.85 |
| CSJ117 1mg | CSJ117 Serum Concentration | Day 1, 4 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Day 1, 2 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 14, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 12, 2 hours post-dose | 2.49 ng/mL | Standard Deviation 4.81 |
| CSJ117 1mg | CSJ117 Serum Concentration | Week 12, pre-dose | 2.20 ng/mL | Standard Deviation 4.61 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 16, pre-dose | 2.16 ng/mL | Standard Deviation 10 |
| CSJ117 2mg | CSJ117 Serum Concentration | Day 1, 2 hours post-dose | 1.86 ng/mL | Standard Deviation 7.36 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 12, 2 hours post-dose | 10.2 ng/mL | Standard Deviation 16.4 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 24, pre-dose | 1.86 ng/mL | Standard Deviation 6.81 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 12, 4 hours post-dose | 10.1 ng/mL | Standard Deviation 16.3 |
| CSJ117 2mg | CSJ117 Serum Concentration | Day 1, 4 hours post-dose | 1.97 ng/mL | Standard Deviation 7.9 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 20, pre-dose | 1.94 ng/mL | Standard Deviation 8.99 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 2, pre-dose | 2.32 ng/mL | Standard Deviation 8.57 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 2, 2 hours post-dose | 2.20 ng/mL | Standard Deviation 8.05 |
| CSJ117 2mg | CSJ117 Serum Concentration | Day 1, pre-dose | 1.34 ng/mL | Standard Deviation 8.02 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 4, pre-dose | 2.89 ng/mL | Standard Deviation 9.03 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 12, pre-dose | 10.3 ng/mL | Standard Deviation 16.8 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 4, 2 hours post-dose | 3.19 ng/mL | Standard Deviation 9.01 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 8, pre-dose | 6.79 ng/mL | Standard Deviation 12 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 8, 2 hours post-dose | 6.94 ng/mL | Standard Deviation 12.2 |
| CSJ117 2mg | CSJ117 Serum Concentration | Week 14, pre-dose | 2.97 ng/mL | Standard Deviation 10.1 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 12, 4 hours post-dose | 15.2 ng/mL | Standard Deviation 20.7 |
| CSJ117 4mg | CSJ117 Serum Concentration | Day 1, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 4mg | CSJ117 Serum Concentration | Day 1, 2 hours post-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 4mg | CSJ117 Serum Concentration | Day 1, 4 hours post-dose | 0.214 ng/mL | Standard Deviation 1.33 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 2, pre-dose | 2.00 ng/mL | Standard Deviation 4.74 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 2, 2 hours post-dose | 1.66 ng/mL | Standard Deviation 3.51 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 4, pre-dose | 2.86 ng/mL | Standard Deviation 5.11 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 4, 2 hours post-dose | 3.59 ng/mL | Standard Deviation 5.69 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 8, pre-dose | 11.5 ng/mL | Standard Deviation 15.8 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 8, 2 hours post-dose | 11.1 ng/mL | Standard Deviation 14.7 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 12, pre-dose | 14.6 ng/mL | Standard Deviation 20.3 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 12, 2 hours post-dose | 14.3 ng/mL | Standard Deviation 20.3 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 14, pre-dose | 1.59 ng/mL | Standard Deviation 4.43 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 16, pre-dose | 0.424 ng/mL | Standard Deviation 1.92 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 20, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 4mg | CSJ117 Serum Concentration | Week 24, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 8mg | CSJ117 Serum Concentration | Day 1, 2 hours post-dose | 0.157 ng/mL | Standard Deviation 0.947 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 14, pre-dose | 7.26 ng/mL | Standard Deviation 15.7 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 8, pre-dose | 39.3 ng/mL | Standard Deviation 51 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 4, 2 hours post-dose | 13.8 ng/mL | Standard Deviation 22.2 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 4, pre-dose | 12.0 ng/mL | Standard Deviation 19.5 |
| CSJ117 8mg | CSJ117 Serum Concentration | Day 1, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 16, pre-dose | 2.53 ng/mL | Standard Deviation 8.1 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 2, 2 hours post-dose | 7.66 ng/mL | Standard Deviation 7.83 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 2, pre-dose | 6.58 ng/mL | Standard Deviation 7.61 |
| CSJ117 8mg | CSJ117 Serum Concentration | Day 1, 4 hours post-dose | 0.924 ng/mL | Standard Deviation 2.58 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 24, pre-dose | 0.00 ng/mL | Standard Deviation 0 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 20, pre-dose | 0.163 ng/mL | Standard Deviation 1.19 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 12, 4 hours post-dose | 46.7 ng/mL | Standard Deviation 52.2 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 12, 2 hours post-dose | 45.7 ng/mL | Standard Deviation 49.7 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 12, pre-dose | 49.5 ng/mL | Standard Deviation 62.1 |
| CSJ117 8mg | CSJ117 Serum Concentration | Week 8, 2 hours post-dose | 39.8 ng/mL | Standard Deviation 49.9 |
Secondary
Number of Participants With Anti-CSJ117 Antibodies
Immunogenicity (antibody formation against CSJ117) was evaluated in serum by a validated bridging electrochemiluminescence immunoassay (ECLIA).
Time frame: Day 1 and Weeks 2, 4, 8, 12, 14, 16, 20 and 24
Population: Participants in the Safety Analysis Set with a valid measurement for the outcome measure. Safety Analysis Set is defined as participants who received at least one dose of double-blind treatment. The number analyzed per row represents participants with data at the corresponding time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Positive | 19 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Negative | 11 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Negative | 30 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Positive | 8 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Positive | 15 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Negative | 9 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Negative | 27 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Positive | 6 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Negative | 7 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Negative | 17 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Negative | 7 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Positive | 24 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Negative | 9 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Positive | 17 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Positive | 17 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Positive | 19 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Negative | 26 Participants |
| CSJ117 0.5mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Positive | 7 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Negative | 33 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Negative | 11 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Positive | 22 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Negative | 6 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Positive | 16 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Positive | 17 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Positive | 15 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Negative | 9 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Positive | 3 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Negative | 31 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Positive | 17 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Positive | 4 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Negative | 29 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Negative | 8 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Positive | 6 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Negative | 10 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Positive | 19 Participants |
| CSJ117 1mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Negative | 16 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Negative | 3 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Positive | 27 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Positive | 23 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Negative | 26 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Negative | 5 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Positive | 23 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Negative | 3 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Positive | 30 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Negative | 5 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Positive | 6 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Positive | 26 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Positive | 11 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Negative | 31 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Negative | 31 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Negative | 10 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Positive | 6 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Positive | 26 Participants |
| CSJ117 2mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Negative | 6 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Positive | 10 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Positive | 45 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Positive | 50 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Negative | 66 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Negative | 65 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Positive | 10 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Negative | 49 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Positive | 25 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Negative | 22 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Negative | 19 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Positive | 52 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Negative | 13 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Positive | 46 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Negative | 12 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Positive | 46 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Negative | 13 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Negative | 13 Participants |
| CSJ117 4mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Positive | 43 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Positive | 24 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Positive | 46 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Negative | 47 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Negative | 7 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Positive | 10 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Negative | 64 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Positive | 46 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Negative | 63 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Positive | 54 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Positive | 11 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Negative | 6 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Positive | 47 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Negative | 11 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Positive | 45 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Positive | 60 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Negative | 8 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Negative | 6 Participants |
| CSJ117 8mg | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Negative | 18 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Negative | 53 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Negative | 49 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Positive | 14 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Positive | 7 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 4 | Negative | 57 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 14 | Negative | 49 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Positive | 13 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 2 | Negative | 56 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Negative | 47 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Negative | 49 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Negative | 58 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 24 | Positive | 7 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Negative | 63 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Day 1 | Positive | 12 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 20 | Positive | 8 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 16 | Positive | 7 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 12 | Positive | 13 Participants |
| Placebo | Number of Participants With Anti-CSJ117 Antibodies | Week 8 | Positive | 9 Participants |
Secondary
Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
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.
Time frame: From first dose of double-blind study treatment up to last dose (Week 12)
Population: Safety Analysis Set defined as participants who received at least one dose of double-blind treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Moderate AEs | 6 Participants |
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs leading to discontinuation | 1 Participants |
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Severe AEs | 1 Participants |
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | At least one AE | 12 Participants |
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 1 Participants |
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Mild AEs | 5 Participants |
| CSJ117 0.5mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Study treatment-related AEs | 0 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Moderate AEs | 2 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Severe AEs | 0 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Mild AEs | 8 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Study treatment-related AEs | 1 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | At least one AE | 10 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs leading to discontinuation | 0 Participants |
| CSJ117 1mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 0 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Mild AEs | 6 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | At least one AE | 13 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Moderate AEs | 7 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Severe AEs | 0 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Study treatment-related AEs | 1 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 0 Participants |
| CSJ117 2mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs leading to discontinuation | 0 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Study treatment-related AEs | 2 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Severe AEs | 1 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | At least one AE | 22 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Moderate AEs | 12 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Mild AEs | 9 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs leading to discontinuation | 0 Participants |
| CSJ117 4mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 0 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Mild AEs | 13 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Severe AEs | 0 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Study treatment-related AEs | 4 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | At least one AE | 25 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs leading to discontinuation | 0 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 0 Participants |
| CSJ117 8mg | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Moderate AEs | 12 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Severe AEs | 0 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | SAEs | 1 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | At least one AE | 23 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Mild AEs | 13 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Study treatment-related AEs | 2 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | Moderate AEs | 10 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period | AEs leading to discontinuation | 2 Participants |