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CompletedNCT03299686Updated Oct 8, 2021Results posted

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

A Phase 2 interventional study of CJM112 and Placebo to CJM112 in Asthma, sponsored by Novartis Pharmaceuticals. Completed at 29 sites in 8 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-10-08.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
118
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • Asthma

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Keywords

  • Asthma, allergic, eosinophilic, non-T2 high, allergy triggered asthma, reactive asthma, asthma attack, difficulty breathing
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
118 participants (actual)

Study arms

  • Experimental
    CJM112

    Study treatment

    Drug: CJM112

  • Placebo comparator
    Placebo to CJM112

    Placebo

    Other: Placebo to CJM112

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

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

06

Results

Posted Aug 6, 2020

Participant flow

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

Treatment Epoch
Participant flow — Treatment Epoch
MilestoneCJM112 300 mgPlacebo
Started7048
Pd (pharmacodynamics) analysis set6948
Completed5944
Not completed114
Withdrew: Subject/guardian decision20
Withdrew: Physician decision10
Withdrew: Adverse event84
Follow-up Epoch
Participant flow — Follow-up Epoch
MilestoneCJM112 300 mgPlacebo
Started5944
Completed5943
Not completed01
Withdrew: Subject/guardian decision01

Outcome measures

PrimaryChange 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
Reported as:
Mean · Liters
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)
LitersCJM112 300 mgPlacebo
Change From Baseline in Forced Expiratory Volume in One Second (FEV1)0.043 ± 0.0310.016 ± 0.030
Statistical analysis
  • CJM112 300 mg vs Placebo · Bayesian linear repeated measures model · p = 0.7374 (Probability CJM112 better than placebo) · Mean difference (net): 0.027 · 80% CI -0.029 to 0.082
SecondaryChange 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
Reported as:
Least squares mean · Percent predicted
Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted
Percent predictedCJM112 300 mgPlacebo
Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted1.064 ± 0.9140.151 ± 1.105
Statistical analysis
  • CJM112 300 mg vs Placebo · Mixed Models Analysis · p = 0.263 (1-sided p-value; p-value smaller than 0.1 is considered as statistically significant) · Mean difference (net): 0.913 · 80% CI -0.939 to 2.766
SecondaryChange 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
Reported as:
Least squares mean · units on scale
Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score
units on scaleCJM112 300 mgPlacebo
Change From Baseline in Asthma Control Questionnaire 6 (ACQ6) Score-0.93 ± 0.09-0.71 ± 0.11
Statistical analysis
  • CJM112 300 mg vs Placebo · Mixed Models Analysis · p = 0.061 (1-sided p-value; p-value smaller than 0.1 is considered as statistically significant) · Mean difference (net): -0.22 · 80% CI -0.41 to -0.04
SecondaryChange 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
Reported as:
Least squares mean · units on scale
Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score
units on scaleCJM112 300 mgPlacebo
Change From Baseline in Asthma Control Questionnaire 7 (ACQ7) Score-0.83 ± 0.08-0.60 ± 0.10
Statistical analysis
  • CJM112 300 mg vs Placebo · Mixed Models Analysis · p = 0.040 (1-sided p-value; p-value smaller than 0.1 is considered as statistically significant) · Mean difference (net): -0.23 · 80% CI -0.40 to -0.06
SecondaryPercentage 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
Reported as:
Count of participants · Participants
Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score
ParticipantsCJM112 300 mgPlacebo
Percentage of Patients With at Least 0.5 Decrease in ACQ7 Score3819
SecondaryPercentage 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
Reported as:
Count of participants · Participants
Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment
ParticipantsCJM112 300 mgPlacebo
Percentage of Patients With Adverse Events (AEs) Leading to Discontinuation of Study Treatment84

Adverse events

Collected over 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. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CJM112 300 mg0/70 (0%)3/70 (4.3%)55/70 (78.6%)
Placebo0/48 (0%)2/48 (4.2%)38/48 (79.2%)
Most frequent serious events
Most frequent serious events
EventCJM112 300 mgPlacebo
Stress cardiomyopathyCardiac disorders0/701/48
PneumoniaInfections and infestations0/701/48
AstheniaGeneral disorders1/700/48
Urinary tract infectionInfections and infestations1/700/48
DepressionPsychiatric disorders1/700/48
Asthmatic crisisRespiratory, thoracic and mediastinal disorders1/700/48
Most frequent other events
Showing 10 of 80
Most frequent other events
EventCJM112 300 mgPlacebo
AsthmaRespiratory, thoracic and mediastinal disorders16/7013/48
NasopharyngitisInfections and infestations16/706/48
HeadacheNervous system disorders8/706/48
Back painMusculoskeletal and connective tissue disorders3/705/48
CoughRespiratory, thoracic and mediastinal disorders4/704/48
BronchitisInfections and infestations5/703/48
DiarrhoeaGastrointestinal disorders3/703/48
FatigueGeneral disorders4/703/48
Oropharyngeal painRespiratory, thoracic and mediastinal disorders3/703/48
RashSkin and subcutaneous tissue disorders1/703/48

Baseline characteristics

Age, Continuous
Age, Continuous(Years)CJM112 300 mgPlaceboTotal
Mean57.1 ± 12.7955.9 ± 11.6256.6 ± 12.29
Sex: Female, Male
Sex: Female, Male(Participants)CJM112 300 mgPlaceboTotal
Female393271
Male311647
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)CJM112 300 mgPlaceboTotal
Asian202
Black or African American617
Other101
White6147108
07

Study locations

29 sites
  • Novartis Investigative Site
    Fullerton, California 92835, United States
  • Novartis Investigative Site
    Riverside, California 92506, United States
  • Novartis Investigative Site
    Denver, Colorado 80206, United States
  • Novartis Investigative Site
    Boston, Massachusetts 02115, United States
  • Novartis Investigative Site
    Saint Louis, Missouri 63110, United States
  • Novartis Investigative Site
    Raleigh, North Carolina 27607, United States
  • Novartis Investigative Site
    Medford, Oregon 97504, United States
  • Novartis Investigative Site
    Spartanburg, South Carolina 29303, United States
  • Novartis Investigative Site
    Mar del Plata, Buenos Aires 7600, Argentina
  • Novartis Investigative Site
    Santa Fe, Rosario S2000DBS, Argentina
  • Novartis Investigative Site
    Jette, Brussel 1090, Belgium
  • Novartis Investigative Site
    Gent, 9000, Belgium
  • Novartis Investigative Site
    Liege, 4000, Belgium
  • Novartis Investigative Site
    Aalborg, DK 9000, Denmark
  • Novartis Investigative Site
    Copenhagen NV, 2400, Denmark
  • Novartis Investigative Site
    Hvidovre, 2650, Denmark
  • Novartis Investigative Site
    Odense C, DK 5000, Denmark
  • Novartis Investigative Site
    Montpellier cedex 5, Herault 34059, France
  • Novartis Investigative Site
    Lyon Cedex 04, 69317, France
  • Novartis Investigative Site
    Berlin, 10117, Germany
  • Novartis Investigative Site
    Berlin, 12159, Germany
  • Novartis Investigative Site
    Grosshansdorf, 22927, Germany
  • Novartis Investigative Site
    Mainz, 55131, Germany
  • Novartis Investigative Site
    Wiesbaden, 65187, Germany
  • Novartis Investigative Site
    Jerusalem, 91120, Israel
  • Novartis Investigative Site
    Jerusalem, Israel
  • Novartis Investigative Site
    Rehovot, 76100, Israel
  • Novartis Investigative Site
    Levice, 034 01, Slovakia
  • Novartis Investigative Site
    Spisska Nova Ves, 052 01, Slovakia
08

References and documents

Study documents

  • Study protocol · May 15, 2018
  • Statistical analysis plan · Aug 14, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

09

Registry details

Key details

Study ID
NCT03299686
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Oct 3, 2017
Start date
Nov 6, 2017
Primary completion
Apr 8, 2019
Completion
Jul 8, 2019
Results posted
Aug 6, 2020
Last update
Oct 8, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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