Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Severe Asthma (NCT NCT03299686)

Last Updated: 2021-10-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

118 participants

Primary outcome timeframe

Baseline, Day 92

Results posted on

2021-10-08

Participant Flow

Participants were from Argentina (2), Belgium (3), Germany (5), Denmark (4), France (2), Israel (3), Slovakia (2), The United States (7)

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.

Participant milestones

Participant milestones
Measure	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	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
Treatment Epoch STARTED	70	48
Treatment Epoch PD (Pharmacodynamics) Analysis Set	69	48
Treatment Epoch COMPLETED	59	44
Treatment Epoch NOT COMPLETED	11	4
Follow-up Epoch STARTED	59	44
Follow-up Epoch COMPLETED	59	43
Follow-up Epoch NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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
Treatment Epoch Subject/Guardian Decision	2	0
Treatment Epoch Physician Decision	1	0
Treatment Epoch Adverse Event	8	4
Follow-up Epoch Subject/Guardian Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CJM112 300 mg n=70 Participants 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 n=48 Participants 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 n=118 Participants Total of all reporting groups
Age, Continuous	57.1 Years STANDARD_DEVIATION 12.79 • n=5 Participants	55.9 Years STANDARD_DEVIATION 11.62 • n=7 Participants	56.6 Years STANDARD_DEVIATION 12.29 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	32 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	16 Participants n=7 Participants	47 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	61 Participants n=5 Participants	47 Participants n=7 Participants	108 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 92

Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints.

Outcome measures

Outcome measures
Measure	CJM112 300 mg n=53 Participants 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 n=36 Participants 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
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)	0.043 Liters Standard Deviation 0.031	0.016 Liters Standard Deviation 0.030

SECONDARY outcome

Timeframe: Baseline, Day 92

Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable FEV1 data at both timepoints

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.

Outcome measures

Outcome measures
Measure	CJM112 300 mg n=53 Participants 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 n=36 Participants 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
Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted	1.064 Percent predicted Standard Error 0.914	0.151 Percent predicted Standard Error 1.105

SECONDARY outcome

Timeframe: Baseline, Day 92

Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ6 data at both timepoints

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.

Outcome measures

Outcome measures
Measure	CJM112 300 mg n=56 Participants 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 n=41 Participants 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
Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score	-0.93 units on scale Standard Error 0.09	-0.71 units on scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline, Day 92

Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints

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.

Outcome measures

Outcome measures
Measure	CJM112 300 mg n=53 Participants 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 n=36 Participants 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
Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score	-0.83 units on scale Standard Error 0.08	-0.60 units on scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, Day 92

Population: The analysis population included the Pharmacodynamics (PD) analysis set with evaluable ACQ7 data at both timepoints

Outcome measures

Outcome measures
Measure	CJM112 300 mg n=53 Participants 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 n=36 Participants 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
Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score	38 Participants	19 Participants

SECONDARY outcome

Timeframe: 85 days

Population: Safety analysis set: Subjects who received any study drug

Number of patients with at least one adverse event leading to discontinuation of study treatment

Outcome measures

Outcome measures
Measure	CJM112 300 mg n=70 Participants 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 n=48 Participants 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
Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment	8 Participants	4 Participants

Adverse Events

CJM112 300 mg

Serious events: 3 serious events

Other events: 55 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CJM112 300 mg n=70 participants at risk 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 n=48 participants at risk 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
Cardiac disorders Stress cardiomyopathy	0.00% 0/70 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment	2.1% 1/48 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
General disorders Asthenia	1.4% 1/70 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment	0.00% 0/48 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
Infections and infestations Pneumonia	0.00% 0/70 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment	2.1% 1/48 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
Infections and infestations Urinary tract infection	1.4% 1/70 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment	0.00% 0/48 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
Psychiatric disorders Depression	1.4% 1/70 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment	0.00% 0/48 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment
Respiratory, thoracic and mediastinal disorders Asthmatic crisis	1.4% 1/70 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment	0.00% 0/48 • 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 Any sign or symptom that occurs during the study treatment plus the 91 days post treatment

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER