Clinical trial NCT04410523: Study of Efficacy and Safety of CSJ117 in Patients With Severe Uncontrolled Asthma
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Keywords: CSJ117
uncontrolled asthma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-06-01
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12
timeFrame: Baseline, Weeks 8-12
Secondary outcomes:
measure: Average Change From Baseline in FeNO at Week 8 and Week 12
timeFrame: Baseline, Weeks 8-12
measure: Change From Baseline in Morning PEF at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Evening PEF at Week 12
timeFrame: Baseline, Week 12
measure: Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12
timeFrame: Baseline, Weeks 8-12
measure: Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12
timeFrame: Baseline, Weeks 8-12
measure: Change From Baseline in ADSD Score at Week 8 and Week 12
timeFrame: Baseline, Week 8 and Week 12
measure: Change From Baseline in ANSD Score at Week 8 and Week 12
timeFrame: Baseline, Week 8 and Week 12
measure: Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
timeFrame: From first dose of double-blind study treatment up to last dose (Week 12)
measure: Number of Participants With Anti-CSJ117 Antibodies
timeFrame: Day 1 and Weeks 2, 4, 8, 12, 14, 16, 20 and 24
measure: CSJ117 Serum Concentration
timeFrame: 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
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Novartis Investigative Site
state: California
city: Huntington Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Mission Viejo
country: United States
facility: Novartis Investigative Site
state: California
city: San Jose
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Bangor
country: United States
facility: Novartis Investigative Site
state: Maine
city: White Marsh
country: United States
facility: Novartis Investigative Site
state: Maryland
city: North Dartmouth
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Columbia
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Raleigh
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Greenville
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Boerne
country: United States
facility: Novartis Investigative Site
state: Texas
city: McKinney
country: United States
facility: Novartis Investigative Site
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ranelagh, Partido De Berazate
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Salvador
country: Argentina
facility: Novartis Investigative Site
state: Entre Rios
city: Concepcion del Uruguay
country: Argentina
facility: Novartis Investigative Site
state: Entre Ríos
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
state: Rosario
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Mendoza
country: Argentina
facility: Novartis Investigative Site
city: Parana
country: Argentina
facility: Novartis Investigative Site
city: Erpent
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Ruse
country: Bulgaria
facility: Novartis Investigative Site
city: Stara Zagora
country: Bulgaria
facility: Novartis Investigative Site
city: Ajax
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Burlington
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Etobicoke
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Teplice
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Jindrichuv Hradec
country: Czechia
facility: Novartis Investigative Site
city: Lovosice
country: Czechia
facility: Novartis Investigative Site
city: Varnsdorf
country: Czechia
facility: Novartis Investigative Site
city: Peine
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Bamberg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Darmstadt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Witten
country: Germany
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
state: GTM
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
state: GTM
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Balassagyarmat
country: Hungary
facility: Novartis Investigative Site
city: Godollo
country: Hungary
facility: Novartis Investigative Site
city: Komarom
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Osaka city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kodaira
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya-Ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Toshima ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Toshima
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
state: LV
city: Riga
country: Latvia
facility: Novartis Investigative Site
state: LV
city: Daugavpils
country: Latvia
facility: Novartis Investigative Site
city: Daugavpils
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Bulacan
country: Philippines
facility: Novartis Investigative Site
city: Iloilo City
country: Philippines
facility: Novartis Investigative Site
city: Iloilo
country: Philippines
facility: Novartis Investigative Site
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Izhevsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Ulyanovsk
country: Russian Federation
facility: Novartis Investigative Site
city: Levice
country: Slovakia
facility: Novartis Investigative Site
city: Presov
country: Slovakia
facility: Novartis Investigative Site
Study officials:
References: