Study of Efficacy and Safety of CSJ117 in Patients With Severe Uncontrolled Asthma

Asthma Clinical Trial

Official title:

A 12-week, Multicenter, Randomized, Double-blind, Parallel-arm, Placebo-controlled Study to Assess the Efficacy and Safety of CSJ117, When Added to Existing Asthma Therapy in Patients ≥ 18 Years of Age With Severe Uncontrolled Asthma.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04410523
• Other study ID #: CCSJ117A12201C
• Secondary ID: 2019-004905-29
• Status: Terminated
• Phase: Phase 2
• Start date: September 9, 2020
• Est. completion date: September 6, 2022

Study information

• Verified date: July 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy and safety of multiple CSJ117 doses (0.5; 1; 2; 4 and 8 mg) inhaled once daily compared with placebo, when added to standard-of-care (SoC) asthma therapy in adult patients with uncontrolled asthma with respect to change from baseline in FEV1 at the end of 12 weeks of treatment.

Description:

This was a randomized, multicenter, multi-national, double-blind, placebo-controlled, parallel-arm study evaluating the effect of 5 dose levels of CSJ117 in adult subjects with inadequately controlled asthma despite medium to high dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA). Subjects were assigned to one of the following six treatment arms/groups in a ratio of 2:1:1:1:2:2: - Placebo inhaled once daily - CSJ117 0.5 mg inhaled once daily - CSJ117 1.0 mg inhaled once daily - CSJ117 2.0 mg inhaled once daily - CSJ117 4.0 mg inhaled once daily - CSJ117 8.0 mg inhaled once daily The study included: - A screening period of approximately 2 weeks - A single blinded placebo run-in period of 4 weeks (extended to 8 weeks for subjects experiencing an asthma exacerbation or respiratory tract infection during the run-in period) - A double blinded treatment period of 12 weeks - A follow-up period of up to 12 weeks, study drug free, following the last dose of study treatment. Patients who successfully completed 12 weeks of treatment in this study could be offered participation in the Safety Extension Study CCSJ117A12201E1 (NCT04946318).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 335
• Est. completion date: September 6, 2022
• Est. primary completion date: July 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosed asthma
• Male and female patients aged =18 and =75 years
• Patients who have been treated with medium or high dose ICS plus LABA with up to 2 additional controllers
• Morning pre-BD FEV1 value of = 40% and = 85% of the predicted normal
• A positive reversibility test
• ACQ-5 score of = 1.5 at screening and end of run-in visits.

Exclusion Criteria:

• Patients who have a cigarette smoking history of greater than 10 pack years or current smokers
• Pregnant or nursing (lactating) women
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using specified methods of contraception during dosing of study drug and until 12 weeks after last study drug treatment
• Patients with a history of immunodeficiency disease or hepatitis B, untreated and not cured hepatitis C or HIV.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• CSJ117
CSJ117 inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device. CSJ117 = inhaled monoclonal antibody fragment
• Placebo
Run-in period (all arms): Placebo inhaled once daily (in the morning) for 4 weeks. Placebo dosing extended to 8 weeks in case of asthma exacerbation or respiratory tract infection during this period. Treatment period (Placebo arm only): Placebo inhaled once daily (in the morning) for 12 weeks. Delivered via Concept1 device.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Concepcion del Uruguay	Entre Ríos
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Parana
Argentina	Novartis Investigative Site	Ranelagh, Partido De Berazate	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	San Salvador	Entre Rios
Argentina	Novartis Investigative Site	Santa Fe	Rosario
Belgium	Novartis Investigative Site	Erpent
Belgium	Novartis Investigative Site	Liege
Bulgaria	Novartis Investigative Site	Ruse
Bulgaria	Novartis Investigative Site	Stara Zagora
Canada	Novartis Investigative Site	Ajax	Ontario
Canada	Novartis Investigative Site	Burlington	Ontario
Canada	Novartis Investigative Site	Etobicoke	Ontario
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Czechia	Novartis Investigative Site	Jindrichuv Hradec
Czechia	Novartis Investigative Site	Lovosice
Czechia	Novartis Investigative Site	Teplice	CZE
Czechia	Novartis Investigative Site	Varnsdorf
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Peine	Niedersachsen
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Witten
Guatemala	Novartis Investigative Site	Guatemala City	GTM
Guatemala	Novartis Investigative Site	Guatemala City	GTM
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Godollo
Hungary	Novartis Investigative Site	Komarom
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szeged
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Chuo-ku	Tokyo
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka city	Osaka
Japan	Novartis Investigative Site	Setagaya-Ku	Tokyo
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Toshima	Tokyo
Japan	Novartis Investigative Site	Toshima ku	Tokyo
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga	LV
Philippines	Novartis Investigative Site	Bulacan
Philippines	Novartis Investigative Site	Iloilo
Philippines	Novartis Investigative Site	Iloilo City
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Manila
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Russian Federation	Novartis Investigative Site	Izhevsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Ulyanovsk
Slovakia	Novartis Investigative Site	Levice
Slovakia	Novartis Investigative Site	Presov
United States	Novartis Investigative Site	Bakersfield	California
United States	Novartis Investigative Site	Bangor	Maine
United States	Novartis Investigative Site	Boerne	Texas
United States	Novartis Investigative Site	Columbia	Missouri
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	McKinney	Texas
United States	Novartis Investigative Site	Mission Viejo	California
United States	Novartis Investigative Site	North Dartmouth	Massachusetts
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Raleigh	North Carolina
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Jose	California
United States	Novartis Investigative Site	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Czechia,  Germany,  Guatemala,  Hungary,  Japan,  Latvia,  Philippines,  Poland,  Russian Federation,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12	FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.; Pre-dose FEV1 is defined as average of the two FEV1 measurements taken at approximately 45 minutes and 15 minutes prior to dosing.; The baseline pre-dose FEV1 value is defined as the average of the values taken approximately 2 hours 45 minutes and 2 hours 15 minutes prior to the first dose of double-blind treatment at Day 1.; The least-squares means for change from baseline in pre-dose FEV1 averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM).; A positive average change from baseline in pre-dose FEV1 is considered a favorable outcome.	Baseline, Weeks 8-12
Secondary	Average Change From Baseline in FeNO at Week 8 and Week 12	Fractional exhaled Nitric Oxide (FeNO) pre-dose measurements were done at the investigational sites prior to spirometry assessments. FeNO is defined as the mean of two serial measurements. The measurement of exhaled nitric oxide is widely accepted as a non-invasive marker of airway inflammation (inflammation leads to elevation of FeNO).; The baseline FeNO pre-dose measurements were taken at the end of the run-in period.; The least-squares means for change from baseline in FeNO averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM).; A negative average change from baseline in FeNO is considered a favorable outcome.	Baseline, Weeks 8-12
Secondary	Change From Baseline in Morning PEF at Week 12	PEF (Peak Expiratory Flow) is a person's maximum speed of expiration. All participants were instructed to record PEF twice daily before taking any medication using an electronic peak expiratory flow device (eDiary/ePEF), once in the morning and once approximately 12 hours later in the evening at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the eDiary/ePEF.; Mean morning and evening PEF values were calculated by weekly intervals. The baseline values of PEF were the mean values in the run-in period. A positive change from baseline in PEF is considered a favorable outcome.	Baseline, Week 12
Secondary	Change From Baseline in Evening PEF at Week 12	PEF (Peak Expiratory Flow) is a person's maximum speed of expiration. All participants were instructed to record PEF twice daily before taking any medication using an electronic peak expiratory flow device (eDiary/ePEF), once in the morning and once approximately 12 hours later in the evening at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the eDiary/ePEF.; Mean morning and evening PEF values were calculated by weekly intervals. The baseline values of PEF were the mean values in the run-in period. A positive change from baseline in PEF is considered a favorable outcome.	Baseline, Week 12
Secondary	Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12	The Asthma Control Questionnaire-5 (ACQ-5) is a five-item, self-completed questionnaire, which is used as a measure of asthma symptom control. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the overall ACQ-5 score is the mean of all 5 questions, therefore between 0 (totally controlled) and 6 (severely uncontrolled).; The baseline values of ACQ-5 were collected at the end of the run-in period. The least-squares means for change from baseline in ACQ-5 score averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM).; A negative change from baseline in ACQ-5 is considered a favorable outcome.	Baseline, Weeks 8-12
Secondary	Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12	The Asthma Quality of Life Questionnaire+12 (AQLQ+12) is a disease specific questionnaire, which is used as a measure of health-related quality of life. The AQLQ+12 comprises a total of 32 individual questions that span a total of 4 domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The overall AQLQ+12 score is the mean of all 32 individual responses, therefore between 7 and 1 with higher scores indicating less impairment in health-related quality of life.; The baseline values of AQLQ+12 were collected at the end of the run-in period. The least-squares means for change from baseline in AQLQ+12 score averaged between Week 8 and Week 12 visits were obtained from a linear mixed effects model for repeated measures (MMRM).; A positive change from baseline is considered a favorable outcome.	Baseline, Weeks 8-12
Secondary	Change From Baseline in ADSD Score at Week 8 and Week 12	Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) are patient reported outcome measures of asthma symptom severity.; Patients recorded asthma symptoms twice daily in the eDiary. Severity of daytime asthma symptoms were assessed before going to bed and severity of nighttime symptoms upon waking.; Both diaries comprised of 6 items assessing breathing symptoms (difficulty breathing, wheezing, and shortness of breath), chest symptoms (chest tightness and chest pain), and cough symptoms (cough). All items were assessed using an 11-point numeric rating scale ranging from 0 ('None') to 10 ('As bad as you can imagine'). The overall score is the mean of all 6 individual responses, therefore between 0 and 10 with higher scores indicating more severe symptoms.; Mean daily scores of both diaries were calculated by weekly intervals. The baseline values were defined as the average score during the run-in period.; A negative change from baseline is a favorable outcome.	Baseline, Week 8 and Week 12
Secondary	Change From Baseline in ANSD Score at Week 8 and Week 12	Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) are patient reported outcome measures of asthma symptom severity.; Patients recorded asthma symptoms twice daily in the eDiary. Severity of daytime asthma symptoms were assessed before going to bed and severity of nighttime symptoms upon waking.; Both diaries comprised of 6 items assessing breathing symptoms (difficulty breathing, wheezing, and shortness of breath), chest symptoms (chest tightness and chest pain), and cough symptoms (cough). All items were assessed using an 11-point numeric rating scale ranging from 0 ('None') to 10 ('As bad as you can imagine'). The overall score is the mean of all 6 individual responses, therefore between 0 and 10 with higher scores indicating more severe symptoms.; Mean daily scores of both diaries were calculated by weekly intervals. The baseline values were defined as the average score during the run-in period.; A negative change from baseline is a favorable outcome.	Baseline, Week 8 and Week 12
Secondary	Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12	Participants were given a short acting ß2-agonist (SABA) such as salbutamol (100 µg) or albuterol (90 µg) to use as rescue medication throughout the study. Participants recorded in the eDiary, once in the morning and once in the evening, the use of rescue medication (number of puffs of SABA taken in the previous 12 hours). The total number of puffs of SABA taken per day was calculated and the mean daily use of puffs of SABA was derived by weekly intervals.; The baseline value of number of puffs of SABA taken per day is the average of total daily SABA use during the run-in period.; A negative change from baseline is considered a favorable outcome.	Baseline, Week 12
Secondary	Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period	Number of participants with AEs and SAEs, including asthma exacerbations, changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs during the on-treatment period.; The on-treatment period is between the date of first dose of double-blind study treatment and date of the last dose of randomized study treatment.; Grades to characterize the severity of the adverse events were based on the Common Terminology Criteria for Adverse Events (CTCAE). For CTCAE, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.; The number of participants in each category is reported in the table.	From first dose of double-blind study treatment up to last dose (Week 12)
Secondary	Number of Participants With Anti-CSJ117 Antibodies	Immunogenicity (antibody formation against CSJ117) was evaluated in serum by a validated bridging electrochemiluminescence immunoassay (ECLIA).	Day 1 and Weeks 2, 4, 8, 12, 14, 16, 20 and 24
Secondary	CSJ117 Serum Concentration	CSJ117 concentration was determined in serum by a validated immunoassay method. Concentrations below the lower limit of quantification (LLOQ) were treated as "zero".	Day 1 and Week 12: pre-dose, 2 and 4 hours post-dose; Weeks 2, 4 and 8: pre-dose and 4 hours post-dose; Weeks 14, 16, 20 and 24: pre-dose