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 )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: CJM112; Other: Placebo to CJM112	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 6, 2017
• Actual Primary Completion Date: April 8, 2019
• Actual Study Completion Date: July 8, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: CJM112; Study treatment	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.
Placebo Comparator: Placebo to CJM112; Placebo	Other: Placebo to CJM112; Placebo to match CJM112 + standard of care treatment

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.

3. 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.
4. 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.

5. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Novartis Investigative Site

Fullerton, California, United States, 92835

Novartis Investigative Site

Riverside, California, United States, 92506

United States, Colorado

Novartis Investigative Site

Denver, Colorado, United States, 80206

United States, Massachusetts

Novartis Investigative Site

Boston, Massachusetts, United States, 02115

United States, Missouri

Novartis Investigative Site

Saint Louis, Missouri, United States, 63110

United States, North Carolina

Novartis Investigative Site

Raleigh, North Carolina, United States, 27607

United States, Oregon

Novartis Investigative Site

Medford, Oregon, United States, 97504

United States, South Carolina

Novartis Investigative Site

Spartanburg, South Carolina, United States, 29303

Argentina

Novartis Investigative Site

Mar del Plata, Buenos Aires, Argentina, 7600

Novartis Investigative Site

Santa Fe, Rosario, Argentina, S2000DBS

Belgium

Novartis Investigative Site

Jette, Brussel, Belgium, 1090

Novartis Investigative Site

Gent, Belgium, 9000

Novartis Investigative Site

Liege, Belgium, 4000

Denmark

Novartis Investigative Site

Aalborg, Denmark, DK 9000

Novartis Investigative Site

Copenhagen NV, Denmark, 2400

Novartis Investigative Site

Hvidovre, Denmark, 2650

Novartis Investigative Site

Odense C, Denmark, DK 5000

France

Novartis Investigative Site

Montpellier cedex 5, Herault, France, 34059

Novartis Investigative Site

Lyon Cedex 04, France, 69317

Germany

Novartis Investigative Site

Berlin, Germany, 10117

Novartis Investigative Site

Berlin, Germany, 12159

Novartis Investigative Site

Grosshansdorf, Germany, 22927

Novartis Investigative Site

Mainz, Germany, 55131

Novartis Investigative Site

Wiesbaden, Germany, 65187

Israel

Novartis Investigative Site

Jerusalem, Israel, 91120

Novartis Investigative Site

Jerusalem, Israel

Novartis Investigative Site

Rehovot, Israel, 76100

Slovakia

Novartis Investigative Site

Levice, Slovakia, 034 01

Novartis Investigative Site

Spisska Nova Ves, Slovakia, 052 01

Sponsors and Collaborators

Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] May 15, 2018

Statistical Analysis Plan  [PDF] August 14, 2019

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03299686
• Other Study ID Numbers: CCJM112X2204
• First Posted: October 3, 2017
• Results First Posted: August 6, 2020
• Last Update Posted: October 8, 2021
• Last Verified: October 2021

Individual Participant Data (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

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases