Clinical trial NCT04946318: Study of Safety of CSJ117 in Participants With Moderate to Severe Uncontrolled Asthma
Official title: A 24-week, Multicenter, Randomized, Double-blind, Parallel-arm, Placebo-controlled Extension Study to Assess the Safety of CSJ117, When Added to Existing Standard of Care Asthma Therapy in Patients ≥18 Years of Age
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Keywords: CSJ, GINA 2019, Safety
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 136
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 provide safety and tolerability, pharmacokinetics and immunogenicity data for multiple CSJ117 doses inhaled once daily compared with placebo, in adult asthma participants treated with medium or high dose ICS plus LABA alone or with additional asthma controllers (additional controllers allowed: LTRA, LAMA, Theophylline and its derivatives), who have completed the prior phase llb study CCSJ117A12201C (NCT04410523).

Detailed description: This is a 12/24-week Phase llb, multicenter, multi-national, double-blind, randomized, parallel-arm, placebo-controlled extension study to evaluate the safety and tolerability, pharmacokinetics and immunogenicity of 5 dose levels of CSJ117 in adult asthma participants treated with medium or high dose ICS plus LABA alone or with additional asthma controllers (allowed: LTRA, LAMA, theophylline or its derivatives), who have completed the prior core phase llb study CCSJ117A12201C (NCT04410523). The study will include the following three parts:

A Screening period of up to 3 days to assess eligibility.

A Treatment period of 12 or 24 weeks. There are two scenarios on when a participant can enroll into the extension study depending on when the study site is activated for the extension study CCSJ117A12201E1:

* A 24 week treatment period: Participants on each of the five treatment arms (CSJ117 0.5 to 8 mg) or placebo of the core study CCSJ117A12201C, who will enter the extension study after the last Treatment period visit (week 12) of the core study, will be randomized in a 1:1 ratio to continue on their previously assigned CSJ117 dose or placebo from CCSJ117A12201C for 24 weeks, or to first go through a 12-week "washout period" receiving placebo (for the blinding purpose) and then restart on their previously assigned CSJ117 dose or placebo from CCSJ117A12201C for 12 weeks.
* A 12 week treatment period: Participants on each of the five treatment arms (CSJ117 0.5 to 8 mg) or placebo of the core study CCSJ117A12201C, who will enter the extension study after the last Follow-up visit (week 24) of the core study, will restart on their previously assigned CSJ117 dose or placebo from CCSJ117A12201C for 12 weeks.

A Follow-up period of 12 weeks, study drug free, following the last dose of study drug.

Eligibility criteria: Inclusion Criteria:

* All participants must have been treated with a fixed dose combination of fluticasone propionate/salmeterol in one of two doses in stable dose alone or with additional controllers at label approved dosage (allowed only: LTRA, LAMA, Theophylline or its derivatives).
* Participants completing the Treatment period and Follow-up period of study CSJ117A12201C and continuing with study CCSJ117A12201E1 must have completed the Treatment period of CSJ117A12201C (i.e. did not discontinue blinded study treatment prematurely) and Follow-up period of study CSJ117A12201C.

Exclusion Criteria:

* Participants who were enrolled into prior study CSJ117A12201C and developed a significant and/or permanent health condition during the prior study.
* Participants who experienced a serious and drug-related AE in the prior study CSJ117A12201C.
* Participants receiving any prohibited medications.
* Participants with a history or current diagnosis of ECG abnormalities.
* Pregnant or nursing (lactating) women.

Primary outcomes:
measure: Number of treatment emergent adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From start of treatment in the core study and until 30 days after end of treatment in the extension study. Up to 40 weeks.
measure: Number of treatment emergent participant deaths and participant hospitalizations
timeFrame: From start of treatment in the core study and until 30 days after end of treatment in the extension study. Up to 40 weeks.
Secondary outcomes:
measure: Trough plasma concentration (Ctrough) at Steady State
timeFrame: Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.
measure: Terminal Elimination half-life (T1/2) at Steady State
timeFrame: Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.
measure: Change from baseline in Anti-drug immune response
timeFrame: Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.
measure: Change from baseline in Fractional exhaled Nitric Oxide (FeNO) levels
timeFrame: Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.
measure: CSJ117 serum concentration
timeFrame: Participants entering directly after completion of study treatment of core study: Weeks 2, 4, 8, 12, 14, 16, 20, 24, 26, 28 and 36; Participants entering directly after completion of the core study Follow-up period: Weeks 2, 4, 8, 12, 14, 16 and 24.
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: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: White Marsh
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
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: Ranelagh, Partido De Berazate
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
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: Mendoza
country: Argentina
facility: Novartis Investigative Site
city: Parana
country: Argentina
facility: Novartis Investigative Site
city: Erpent
country: Belgium
facility: Novartis Investigative Site
city: Ruse
country: Bulgaria
facility: Novartis Investigative Site
city: Stara Zagora
country: Bulgaria
facility: Novartis Investigative Site
city: Burlington
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Etobicoke
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Teplice
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Lovosice
country: Czechia
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: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Witten
country: Germany
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: 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: Daugavpils
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
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: Krakow
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Levice
country: Slovakia
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: