Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma

AstraZeneca1,061 enrolled

Overview

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

This is a multicentre, randomized, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma on medium to high-dose ICS and at least one additional asthma controller medication with or without OCS. Approximately 1060 subjects will be randomized globally. Subjects 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,061

Conditions

Asthma

Interventions

Experimental: TezepelumabBIOLOGICAL

Tezepelumab subcutaneous injection

PlaceboOTHER

Placebo subcutaneous injection

Eligibility

Sex: ALLMin age: 12 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age. 12-80 * Documented physician-diagnosed asthma for at least 12 months * Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 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 (\<90% for subjects 12-17 yrs) * 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. * 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 subjects with smoking history ≥10 pack-years and subjects using vaping products, including electronic cigarettes. * 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. * Subject randomized in the current study or previous tezepelumab studies.

Locations (289)

Outcomes

Primary Outcomes

Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma

The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. The analysis is based on the primary population (Full Analysis Set)

Time frame: From randomisation to Study Week 52.

Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL

The annual exacerbation rate is based on unadjudicated exacerbations reported by the investigator in the eCRF. This analysis is based on subjects with baseline eosinophils \< 300 cells/uL

Time frame: From randomisation to Study Week 52.

Secondary Outcomes

Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint)

Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint)

Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).

Time frame: From randomisation to Study Week 52

Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint)

Data from ClinicalTrials.gov

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Research Site

Dothan, Alabama, United States

Research Site

Foley, Alabama, United States

Research Site

Gilbert, Arizona, United States

Research Site

Tucson, Arizona, United States

Research Site

Bakersfield, California, United States

Research Site

Encinitas, California, United States

Research Site

Huntington Beach, California, United States

Research Site

Long Beach, California, United States

Research Site

Los Angeles, California, United States

Research Site

Mission Viejo, California, United States

...and 279 more locations

Change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint)

Mean change from baseline at Week 52 in Asthma Symptom Diary. The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4, where 0 indicates no asthma symptoms.

Time frame: From randomisation to Study Week 52

Time to First Asthma Exacerbation

Time to first occurrence of asthma exacerbation post-randomisation, presented as number of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb)

Mean change from baseline at Study Week 52 in FeNO (ppb) measured at site

Time frame: From randomisation to Study Week 52

Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52

Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x \[number of night nebulizer times\] + number of daytime inhaler puffs + 2 x \[number of day nebulizer times\]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52

WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52

WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Class productivity loss is derived by sum of percentage of missed class hours due to asthma and product of percentage of actual hours in class times degree of asthma affecting productivity while in class. Percentage of missed hours in class due to asthma is calculated by number of hours in class missed due to asthma divided by total number of hours in class missed plus number of hours actually in class.

Time frame: From randomisation to Study Week 52

Activity Impairment at Week 52

WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage.

Time frame: From randomisation to Study Week 52

Pharmacokinetics of Tezepelumab

Mean serum trough PK concentrations taken pre-dose at each visit

Time frame: Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 36, Week 52, Week 64

Mean Change From Baseline at Week 52 in EQ-5D-5L VAS

Mean change from baseline at Study Week 52 in EQ-5D-5L VAS. EQ-5D-5L visual analogue scale (VAS) allows subjects to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.

Time frame: At Study Week 52

Clinicians Global Impression of Change at Week 52

CGIC (Clinical global impression of change) is an overall evaluation of response to treatment, conducted by investigator using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse)

Time frame: From randomisation to Study Week 52

Patients Global Impression of Change at Week 52

PGIC (Patient global impression of change) is an overall evaluation of response to treatment, conducted by the patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse).

Time frame: From randomisation to Study Week 52

Patients Global Impression of Severity at Week 52

PGI-S (Patient global impression of severity) is an overall evaluation of patient's perception of overall symptom severity using a 6-point rating scale, ranging from 0 = No symptoms, 1=Very mild symptoms, 2=Mild symptoms, 3=Moderate symptoms, 4=Severe symptoms, 5=Very severe symptoms

Time frame: At Study Week 52

Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL)

Mean change from baseline at Study Week 52 in blood eosinophils (cells/uL)

Time frame: From randomisation to Study Week 52

Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL)

Mean change from baseline at Study Week 52 in total serum IgE (IU/mL)

Time frame: From randomisation to Study Week 52

Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks

Number of participants with asthma specific healthcare utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks

Time frame: From randomisation to Study Week 52

Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)

Mean change from baseline in home based morning PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means)

Mean change from baseline in home based evening PEF (L/min) at Study Week 52. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.

Time frame: From randomisation to Study Week 52

Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52

Mean change from baseline in night time awakenings due to asthma at Study Week 52. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.

Time frame: From randomisation to Study Week 52

Immunogenecity of Tezepelumab

Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post baseline assessments (with \>=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.

Time frame: Baseline, and from time of first dose at Week 0 to end of study at Week 64.

Proportion of Subjects Who Had no Asthma Exacerbations

The proportion of subjects who have no exacerbations is presented as the percentage of subjects with no exacerbations. This is defined as subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.

Time frame: From randomisation to Study Week 52

Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation

The annualized exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF)

Time frame: From randomisation to Study Week 52

Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation

Proportion of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation as recorded by the investigator in the CRF. This is presented as percentage of subjects with at least one asthma exacerbation associated with emergency room visit or hospitalisation.

Time frame: From randomisation to Study Week 52

Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation

The proportion of subjects with no exacerbations is presented as percentage of subjects who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation associated with emergency room or hospitalisation during this period.

Time frame: From randomisation to Study Week 52