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Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Severe Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03299686
Recruitment Status : Completed
First Posted : October 3, 2017
Results First Posted : August 6, 2020
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: CJM112
Other: Placebo to CJM112
Enrollment 118
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.
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description 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 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
Period Title: Treatment Epoch
Started 70 48
PD (Pharmacodynamics) Analysis Set [1] 69 48
Completed 59 44
Not Completed 11 4
Reason Not Completed
Subject/Guardian Decision             2             0
Physician Decision             1             0
Adverse Event             8             4
[1]
All subjects with available PD data, who received any study drug, and no major protocol deviations
Period Title: Follow-up Epoch
Started 59 44
Completed 59 43
Not Completed 0 1
Reason Not Completed
Subject/Guardian Decision             0             1
Arm/Group Title CJM112 300 mg Placebo Total
Hide Arm/Group Description 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 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 Total of all reporting groups
Overall Number of Baseline Participants 70 48 118
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 70 participants 48 participants 118 participants
57.1  (12.79) 55.9  (11.62) 56.6  (12.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 48 participants 118 participants
Female
39
  55.7%
32
  66.7%
71
  60.2%
Male
31
  44.3%
16
  33.3%
47
  39.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 48 participants 118 participants
Asian
2
   2.9%
0
   0.0%
2
   1.7%
Black or African American
6
   8.6%
1
   2.1%
7
   5.9%
Other
1
   1.4%
0
   0.0%
1
   0.8%
White
61
  87.1%
47
  97.9%
108
  91.5%
1.Primary Outcome
Title Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints.
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 53 36
Mean (Standard Deviation)
Unit of Measure: Liters
0.043  (0.031) 0.016  (0.030)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CJM112 300 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7374
Comments Probability CJM112 better than placebo
Method Bayesian linear repeated measures model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.027
Confidence Interval (2-Sided) 80%
-0.029 to 0.082
Parameter Dispersion
Type: Standard Deviation
Value: 0.043
Estimation Comments [Not Specified]
Other Statistical Analysis Lower limit and upper limit represents the Credibility Interval from the Bayesian analysis.
2.Secondary Outcome
Title Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 53 36
Least Squares Mean (Standard Error)
Unit of Measure: Percent predicted
1.064  (0.914) 0.151  (1.105)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CJM112 300 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.263
Comments 1-sided p-value; p-value smaller than 0.1 is considered as statistically significant
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.913
Confidence Interval (2-Sided) 80%
-0.939 to 2.766
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.434
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ6 data at both timepoints
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 56 41
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
-0.93  (0.09) -0.71  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CJM112 300 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments 1-sided p-value; p-value smaller than 0.1 is considered as statistically significant
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.22
Confidence Interval (2-Sided) 80%
-0.41 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 53 36
Least Squares Mean (Standard Error)
Unit of Measure: units on scale
-0.83  (0.08) -0.60  (0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CJM112 300 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments 1-sided p-value; p-value smaller than 0.1 is considered as statistically significant
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.23
Confidence Interval (2-Sided) 80%
-0.40 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.13
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 53 36
Measure Type: Count of Participants
Unit of Measure: Participants
38
  71.7%
19
  52.8%
6.Secondary Outcome
Title Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment
Hide Description Number of patients with at least one adverse event leading to discontinuation of study treatment
Time Frame 85 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: Subjects who received any study drug
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 70 48
Measure Type: Count of Participants
Unit of Measure: Participants
8
  11.4%
4
   8.3%
Time Frame Adverse events were collected from first dose of study treatment until end of study treatment plus 91 days post treatment, up to maximum duration of 6 months
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
 
Arm/Group Title CJM112 300 mg Placebo
Hide Arm/Group Description 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 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
All-Cause Mortality
CJM112 300 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/70 (0.00%)   0/48 (0.00%) 
Hide Serious Adverse Events
CJM112 300 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   3/70 (4.29%)   2/48 (4.17%) 
Cardiac disorders     
Stress cardiomyopathy  1  0/70 (0.00%)  1/48 (2.08%) 
General disorders     
Asthenia  1  1/70 (1.43%)  0/48 (0.00%) 
Infections and infestations     
Pneumonia  1  0/70 (0.00%)  1/48 (2.08%) 
Urinary tract infection  1  1/70 (1.43%)  0/48 (0.00%) 
Psychiatric disorders     
Depression  1  1/70 (1.43%)  0/48 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthmatic crisis  1  1/70 (1.43%)  0/48 (0.00%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
CJM112 300 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   55/70 (78.57%)   38/48 (79.17%) 
Cardiac disorders     
Arrhythmia supraventricular  1  0/70 (0.00%)  1/48 (2.08%) 
Endocrine disorders     
Hypothyroidism  1  0/70 (0.00%)  1/48 (2.08%) 
Gastrointestinal disorders     
Abdominal pain  1  0/70 (0.00%)  1/48 (2.08%) 
Constipation  1  0/70 (0.00%)  1/48 (2.08%) 
Diarrhoea  1  3/70 (4.29%)  3/48 (6.25%) 
Gastrooesophageal reflux disease  1  2/70 (2.86%)  1/48 (2.08%) 
Nausea  1  3/70 (4.29%)  2/48 (4.17%) 
Proctalgia  1  0/70 (0.00%)  1/48 (2.08%) 
Toothache  1  1/70 (1.43%)  1/48 (2.08%) 
Vomiting  1  0/70 (0.00%)  2/48 (4.17%) 
General disorders     
Asthenia  1  0/70 (0.00%)  1/48 (2.08%) 
Fatigue  1  4/70 (5.71%)  3/48 (6.25%) 
Injection site haematoma  1  1/70 (1.43%)  1/48 (2.08%) 
Oedema peripheral  1  1/70 (1.43%)  1/48 (2.08%) 
Pyrexia  1  1/70 (1.43%)  1/48 (2.08%) 
Infections and infestations     
Bronchitis  1  5/70 (7.14%)  3/48 (6.25%) 
Conjunctivitis  1  0/70 (0.00%)  1/48 (2.08%) 
Cystitis  1  2/70 (2.86%)  1/48 (2.08%) 
Gastroenteritis  1  2/70 (2.86%)  1/48 (2.08%) 
Gastroenteritis viral  1  0/70 (0.00%)  1/48 (2.08%) 
Lower respiratory tract infection  1  2/70 (2.86%)  0/48 (0.00%) 
Nasopharyngitis  1  16/70 (22.86%)  6/48 (12.50%) 
Oral candidiasis  1  4/70 (5.71%)  0/48 (0.00%) 
Oral herpes  1  0/70 (0.00%)  1/48 (2.08%) 
Pharyngitis  1  1/70 (1.43%)  2/48 (4.17%) 
Respiratory tract infection  1  2/70 (2.86%)  1/48 (2.08%) 
Respiratory tract infection viral  1  2/70 (2.86%)  1/48 (2.08%) 
Rhinitis  1  0/70 (0.00%)  1/48 (2.08%) 
Sinusitis  1  3/70 (4.29%)  0/48 (0.00%) 
Tooth abscess  1  0/70 (0.00%)  1/48 (2.08%) 
Upper respiratory tract infection  1  4/70 (5.71%)  2/48 (4.17%) 
Urinary tract infection  1  1/70 (1.43%)  2/48 (4.17%) 
Viral upper respiratory tract infection  1  2/70 (2.86%)  1/48 (2.08%) 
Injury, poisoning and procedural complications     
Arthropod sting  1  0/70 (0.00%)  1/48 (2.08%) 
Fall  1  0/70 (0.00%)  1/48 (2.08%) 
Ligament sprain  1  0/70 (0.00%)  1/48 (2.08%) 
Rib fracture  1  0/70 (0.00%)  1/48 (2.08%) 
Spinal compression fracture  1  0/70 (0.00%)  1/48 (2.08%) 
Subcutaneous haematoma  1  0/70 (0.00%)  1/48 (2.08%) 
Investigations     
Alanine aminotransferase increased  1  0/70 (0.00%)  2/48 (4.17%) 
Amylase increased  1  0/70 (0.00%)  1/48 (2.08%) 
Aspartate aminotransferase increased  1  0/70 (0.00%)  1/48 (2.08%) 
Blood alkaline phosphatase increased  1  0/70 (0.00%)  1/48 (2.08%) 
Blood bicarbonate decreased  1  0/70 (0.00%)  1/48 (2.08%) 
Blood cholesterol increased  1  1/70 (1.43%)  1/48 (2.08%) 
Blood creatine phosphokinase increased  1  1/70 (1.43%)  1/48 (2.08%) 
Blood creatinine increased  1  1/70 (1.43%)  1/48 (2.08%) 
Blood lactate dehydrogenase increased  1  1/70 (1.43%)  1/48 (2.08%) 
Blood potassium increased  1  0/70 (0.00%)  1/48 (2.08%) 
Blood triglycerides increased  1  0/70 (0.00%)  1/48 (2.08%) 
Gamma-glutamyltransferase increased  1  0/70 (0.00%)  1/48 (2.08%) 
Lipase increased  1  0/70 (0.00%)  1/48 (2.08%) 
Protein urine present  1  0/70 (0.00%)  1/48 (2.08%) 
Red blood cell sedimentation rate increased  1  0/70 (0.00%)  1/48 (2.08%) 
Metabolism and nutrition disorders     
Gout  1  0/70 (0.00%)  1/48 (2.08%) 
Type 2 diabetes mellitus  1  0/70 (0.00%)  1/48 (2.08%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/70 (4.29%)  1/48 (2.08%) 
Back pain  1  3/70 (4.29%)  5/48 (10.42%) 
Intervertebral disc protrusion  1  0/70 (0.00%)  1/48 (2.08%) 
Limb discomfort  1  2/70 (2.86%)  0/48 (0.00%) 
Musculoskeletal pain  1  0/70 (0.00%)  1/48 (2.08%) 
Musculoskeletal stiffness  1  0/70 (0.00%)  1/48 (2.08%) 
Osteoarthritis  1  0/70 (0.00%)  2/48 (4.17%) 
Pain in extremity  1  2/70 (2.86%)  0/48 (0.00%) 
Nervous system disorders     
Dizziness  1  4/70 (5.71%)  0/48 (0.00%) 
Headache  1  8/70 (11.43%)  6/48 (12.50%) 
Intercostal neuralgia  1  0/70 (0.00%)  1/48 (2.08%) 
Migraine  1  2/70 (2.86%)  0/48 (0.00%) 
Sciatica  1  0/70 (0.00%)  1/48 (2.08%) 
Psychiatric disorders     
Insomnia  1  0/70 (0.00%)  1/48 (2.08%) 
Reproductive system and breast disorders     
Prostatitis  1  0/70 (0.00%)  1/48 (2.08%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  16/70 (22.86%)  13/48 (27.08%) 
Cough  1  4/70 (5.71%)  4/48 (8.33%) 
Dysphonia  1  2/70 (2.86%)  0/48 (0.00%) 
Dyspnoea  1  2/70 (2.86%)  0/48 (0.00%) 
Epistaxis  1  0/70 (0.00%)  1/48 (2.08%) 
Haemoptysis  1  0/70 (0.00%)  1/48 (2.08%) 
Nasal congestion  1  0/70 (0.00%)  1/48 (2.08%) 
Oropharyngeal pain  1  3/70 (4.29%)  3/48 (6.25%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/70 (1.43%)  3/48 (6.25%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03299686    
Other Study ID Numbers: CCJM112X2204
First Submitted: August 7, 2017
First Posted: October 3, 2017
Results First Submitted: July 3, 2020
Results First Posted: August 6, 2020
Last Update Posted: October 8, 2021