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

• 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: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: August 7, 2017
• First Posted Date: October 3, 2017
• Results First Submitted Date: July 3, 2020
• Results First Posted Date: August 6, 2020
• Last Update Posted Date: October 8, 2021
• Actual Study Start Date: November 6, 2017
• Actual Primary Completion Date: April 8, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2020)

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: September 27, 2017)

Change from baseline Forced Expiratory Volume 1 (FEV1) [ Time Frame: Baseline, Day 92 ]

Change from baseline FEV1 in mL

Current Secondary Outcome Measures (submitted: July 3, 2020)

• Change From Baseline in Forced Expiratory Volume 1 (FEV1) % of Predicted [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 85 days ]
  Number of patients with at least one adverse event leading to discontinuation of study treatment

Original Secondary Outcome Measures (submitted: September 27, 2017)

• Change from baseline Forced Expiratory Volume 1 (FEV1) % of predicted [ Time Frame: Baseline, Day 92 ]
  Change from baseline FEV1 % of predicted
• Change from baseline in Asthma Control Questionnaire (ACQ) score [ Time Frame: Baseline, Day 92 ]
  Change from baseline in ACQ score
• % of patients with ≥ 0.5 decrease in ACQ score [ Time Frame: Baseline, Day 92 ]
  % of patients with ≥ 0.5 decrease in Asthma Control Questionnaire (ACQ) score
• Adverse Events [ Time Frame: Day 176 (End of Study) ]
  Study treatment discontinuations and adverse events

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Severe Asthma
• Official Title: A Randomized, Subject- and Investigator-blinded, Placebo Controlled, Multi-center, Multiple Dose Study to Assess the Efficacy and Safety of CJM112 in Patients With Inadequately Controlled Moderate to Severe Asthma
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Asthma

Intervention

• Drug: CJM112
  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.
• Other: Placebo to CJM112
  Placebo to match CJM112 + standard of care treatment

Study Arms

• Experimental: CJM112
  Study treatment
  Intervention: Drug: CJM112
• Placebo Comparator: Placebo to CJM112
  Placebo
  Intervention: Other: Placebo to CJM112

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 7, 2020): 118
• Original Estimated Enrollment (submitted: September 27, 2017): 110
• Actual Study Completion Date: July 8, 2019
• Actual Primary Completion Date: April 8, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Denmark, France, Germany, Israel, Slovakia, United States

Administrative Information

• NCT Number: NCT03299686
• Other Study ID Numbers: CCJM112X2204
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

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

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: October 2021