Asthma
Conditions
Keywords
Asthma, allergic, eosinophilic, non-T2 high, allergy triggered asthma, reactive asthma, asthma attack, difficulty breathing
Brief summary
An unmet medical need exists for patients with moderate and severe asthma who continue to demonstrate symptoms despite being on standard of care medications, and are not eligible for other biologic therapies developed or in development for T2-high(allergic/eosinophilic) asthma. The purpose of this study was to determine if CJM112, an anti-IL-17A antibody, displayed the clinical efficacy and safety profile to support further development in patients with inadequately controlled moderate to severe asthma with low IgE and low circulating eosinophil levels.
Detailed description
After an initial screening visit, run-in period and baseline assessments, the eligible subjects entered the treatment period and were randomized in a 3:2 ratio to one of the two treatment groups: * 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12 (Day 85) + standard of care treatment. * Matching placebo + standard of care treatment. After completion of the last dose on Day 85 of treatment period, subjects returned for the final efficacy assessment on Day 92. Following the treatment period, all subjects entered a 13-week safety follow-up period, including the End of Study (EoS) visit on Day 176.
Interventions
DRUGCJM112
300 mg CJM112 (Study treatment) s.c. injection received per week for the first 4 weeks, followed by once every two weeks up to Week 12 (Day 85) + standard of care treatment.
OTHERPlacebo to CJM112
Placebo to match CJM112 + standard of care treatment
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
1. Patients with a physician-diagnosed history of moderate to severe asthma for a period of at least one year prior to screening. 2. Patients on a stable therapy regimen of asthma for at least 3 months prior to screening with at least medium dose inhaled glucocorticoid and at least one additional asthma controller medication (such as inhaled long-acting bronchodilator, leukotriene antagonist, theophylline, stable low dose glucocorticoid, etc). 3. Acceptable and reproducible spirometry with FEV1 ≥ 40 and ≤ 90% of predicted at screening and baseline (re-testing is allowed once). 4. ACQ score ≥ 1.5 at screening and baseline (re-testing is allowed once). 5. Total serum IgE \< 150 IU/mL 6. Peripheral blood eosinophils \<300/μL
Exclusion criteria
1. Previous use of biologics or other concomitant medications within the time periods specified in the SOM/protocol. 2. History of ongoing, chronic, or recurrent moderate or severe infectious disease. 3. Patients who have smoked or inhaled nicotine or tobacco products within the 6 month period prior to Visit 1 or who have a smoking history of greater than 10 pack years. 4. Patients who have had an asthma attack/exacerbation requiring systemic corticosteroids for at least 3 continuous days within 4 weeks prior to screening. 5. Patients who have had a respiratory tract infection or asthma worsening within 4 weeks prior to Visit 1 or during the screening period. 6. Women of child-bearing potential unless they use highly effective methods of contraception during dosing and for 13 weeks after stopping of investigational drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | Baseline, Day 92 | The primary efficacy analysis assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in Liters compared to placebo on Day 92. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted | Baseline, Day 92 | The secondary efficacy analyses assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in % of predicted compared to placebo on Day 92. Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1% of predicted is defined as FEV1% of the patient divided by the average FEV1% in the population for any person of similar age, sex and body composition. Pre-bronchodilator FEV1% of predicted was directly provided as part of the spirometry assessment. |
| Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score | Baseline, Day 92 | The ACQ-6 is a validated asthma assessment tool that consists of 6 self-assessment questions. Each item on the ACQ-6 has a possible score ranging from 0 to 6 and the total score is the mean of all responses. The seven-point response scale goes from 0 = 'totally controlled' to 6 = 'severely uncontrolled. Negative change from baseline values indicate improved asthma control. |
| Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score | Baseline, Day 92 | The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. |
| Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score | Baseline, Day 92 | The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. An ACQ7 responder is defined as a patient with a decrease in score of greater or equal to 0.5 when compared to baseline. |
| Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment | 85 days | Number of patients with at least one adverse event leading to discontinuation of study treatment |
Countries
Argentina, Belgium, Denmark, France, Germany, Israel, Slovakia, United States
Participant flow
Recruitment details
Participants were from Argentina (2), Belgium (3), Germany (5), Denmark (4), France (2), Israel (3), Slovakia (2), The United States (7)
Pre-assignment details
After an initial screening visit, run-in period and baseline assessments, the eligible subjects entered the treatment period and were randomized in a 3:2 ratio to one of the two treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| CJM112 300 mg Study treatment: 300 mg CJM112 s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12 | 70 |
| Placebo Placebo to CJM112: Placebo s.c. injection received once per week for the first 4 weeks, followed by once every two weeks up to Week 12 | 48 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Epoch | Subject/Guardian Decision | 0 | 1 |
| Treatment Epoch | Adverse Event | 8 | 4 |
| Treatment Epoch | Physician Decision | 1 | 0 |
| Treatment Epoch | Subject/Guardian Decision | 2 | 0 |
Baseline characteristics
| Characteristic | CJM112 300 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.1 Years STANDARD_DEVIATION 12.79 | 55.9 Years STANDARD_DEVIATION 11.62 | 56.6 Years STANDARD_DEVIATION 12.29 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 61 Participants | 47 Participants | 108 Participants |
| Sex: Female, Male Female | 39 Participants | 32 Participants | 71 Participants |
| Sex: Female, Male Male | 31 Participants | 16 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 48 |
| other Total, other adverse events | 55 / 70 | 38 / 48 |
| serious Total, serious adverse events | 3 / 70 | 2 / 48 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
The primary efficacy analysis assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in Liters compared to placebo on Day 92. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment.
Time frame: Baseline, Day 92
Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CJM112 300 mg | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | 0.043 Liters | Standard Deviation 0.031 |
| Placebo | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) | 0.016 Liters | Standard Deviation 0.03 |
p-value: 0.737480% CI: [-0.029, 0.082]Bayesian linear repeated measures model
Secondary
Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score
The ACQ-6 is a validated asthma assessment tool that consists of 6 self-assessment questions. Each item on the ACQ-6 has a possible score ranging from 0 to 6 and the total score is the mean of all responses. The seven-point response scale goes from 0 = 'totally controlled' to 6 = 'severely uncontrolled. Negative change from baseline values indicate improved asthma control.
Time frame: Baseline, Day 92
Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ6 data at both timepoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CJM112 300 mg | Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score | -0.93 units on scale | Standard Error 0.09 |
| Placebo | Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score | -0.71 units on scale | Standard Error 0.11 |
p-value: 0.06180% CI: [-0.41, -0.04]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score
The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.
Time frame: Baseline, Day 92
Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CJM112 300 mg | Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score | -0.83 units on scale | Standard Error 0.08 |
| Placebo | Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score | -0.60 units on scale | Standard Error 0.1 |
p-value: 0.0480% CI: [-0.4, -0.06]Mixed Models Analysis
Secondary
Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted
The secondary efficacy analyses assessed the effect of CJM112 on the absolute change from baseline in trough FEV1 in % of predicted compared to placebo on Day 92. Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. FEV1% of predicted is defined as FEV1% of the patient divided by the average FEV1% in the population for any person of similar age, sex and body composition. Pre-bronchodilator FEV1% of predicted was directly provided as part of the spirometry assessment.
Time frame: Baseline, Day 92
Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CJM112 300 mg | Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted | 1.064 Percent predicted | Standard Error 0.914 |
| Placebo | Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted | 0.151 Percent predicted | Standard Error 1.105 |
p-value: 0.26380% CI: [-0.939, 2.766]Mixed Models Analysis
Secondary
Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment
Number of patients with at least one adverse event leading to discontinuation of study treatment
Time frame: 85 days
Population: Safety analysis set: Subjects who received any study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CJM112 300 mg | Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment | 8 Participants |
| Placebo | Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment | 4 Participants |
Secondary
Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score
The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function. An ACQ7 responder is defined as a patient with a decrease in score of greater or equal to 0.5 when compared to baseline.
Time frame: Baseline, Day 92
Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CJM112 300 mg | Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score | 38 Participants |
| Placebo | Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score | 19 Participants |