Clinical trial NCT03927157: Study to Evaluate Tezepelumab in Adults With Severe Uncontrolled Asthma
Official title: A Regional, Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults With Severe Uncontrolled Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Uncontrolled Asthma
Severe Uncontrolled Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2019-04-25
Enrollment: 405
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Primary purpose: TREATMENT

Brief summary: A Regional, Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults with Severe Uncontrolled Asthma

Detailed description: This is a regional, multicentre, randomized, double-blind, placebo controlled, parallel group, phase 3 study designed to evaluate the efficacy and safety of 210 mg Q4W (SC) of tezepelumab in adults with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 396 participants will be randomized regionally (China/non-China). Participants will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks

Eligibility criteria: Inclusion Criteria:

* Age. 18-80
* Documented physician-diagnosed asthma for at least 12 months
* Participants who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 6 months.
* Documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months.
* At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.
* Morning pre-BD FEV1 \<80% predicted normal
* Evidence of asthma as documented by either: Documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months OR Post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening.
* Documented history of at least 2 asthma exacerbation events within 12 months, and at least one of the exacerbations should occur during the treatment of medium-to-high dose ICS.
* ACQ-6 score ≥1.5 at screening and on day of randomization

Exclusion Criteria:

* Pulmonary disease other than asthma.
* History of cancer.
* History of a clinically significant infection.
* Current smokers or participants with smoking history ≥10 pack-yrs.
* History of chronic alcohol or drug abuse within 12 months.
* Hepatitis B, C or HIV.
* Pregnant or breastfeeding.
* History of anaphylaxis following any biologic therapy.
* participant randomized in the current study or previous tezepelumab studies.

Primary outcomes:
measure: Annualized asthma exacerbation rate (AERR)
timeFrame: Randomization to Week 52
Secondary outcomes:
measure: Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1)
timeFrame: Randomization, Week 52
measure: Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(S)+12) total score
timeFrame: Randomization， Week 52
measure: Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) Score
timeFrame: Randomization, Week 52
measure: Change from baseline in weekly mean daily Asthma Symptom Diary score
timeFrame: Randomization, Week 52
measure: Time to first asthma exacerbation
timeFrame: Randomization to Week 52
measure: Change from baseline in fractional exhaled nitric oxide
timeFrame: Randomization, Week 52
measure: Change from baseline in weekly mean rescue medication use
timeFrame: Randomization, Week 52
measure: Number of participants with asthma specific resource utilization (e.g.,eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications)
timeFrame: Randomization to Week 52
measure: Serum trough concentrations
timeFrame: Baseline to Week 64
measure: European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score
timeFrame: Randomization, Week 52
measure: Change from baseline in peripheral blood eosinophils
timeFrame: Randomization, Week 52
measure: Change from baseline in total serum IgE
timeFrame: Randomization, Week 52
measure: Change from baseline in weekly mean morning and evening peak expiratory flow (PEF)
timeFrame: Randomization, Week 52
measure: Change from baseline in weekly mean number of night time awakenings
timeFrame: Randomization, Week 52
measure: Immunogenicity anti-drug antibodies
timeFrame: Baseline to Week 64
measure: Proportion of participants who did not experience an asthma exacerbation
timeFrame: Week 52
measure: Annualized rate of exacerbations associated with emergency room (ER) visit or hospitalizations
timeFrame: Randomization to Week 52
Other outcomes:
Locations:
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hengyang
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Huzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jinhua
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Linyi
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Quanzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shengyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Urumchi
country: China
facility: Research Site
city: Weifang
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xining
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhuhai
country: China
facility: Research Site
city: Zibo
country: China
facility: Research Site
city: Zunyi
country: China
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Jeonju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Iloilo City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
Study officials:
affiliation: Guangzhou institute of Respiratory Disease, China
name: Nanshan Zhong, Bachelor
role: PRINCIPAL_INVESTIGATOR
References: