Study to Evaluate Tezepelumab in Adults With Severe Uncontrolled Asthma
- Conditions
- Asthma
- Interventions
- Other: Placebo
- Registration Number
- NCT03927157
- Lead Sponsor
- AstraZeneca
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 405
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo: Placebo subcutaneous injection
- Primary Outcome Measures
Name Time Method Annualized asthma exacerbation rate (AERR) Randomization to Week 52 The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 52 weeks.
- Secondary Outcome Measures
Name Time Method Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(S)+12) total score Randomization， Week 52 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 participants. 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).
Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) Randomization, Week 52 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.
Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) Score Randomization, Week 52 Mean 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.
Change from baseline in fractional exhaled nitric oxide Randomization, Week 52 Mean change from baseline in FENO (ppb) at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers
Serum trough concentrations Baseline to Week 64 Serum trough concentrations (pre-dose samples) at each scheduled visit to evaluate the pharmacokinetics (PK) of tezepelumab
Change from baseline in weekly mean rescue medication use Randomization, Week 52 Mean change from baseline in weekly mean rescue medication use at Week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on other asthma control metrics. The number of rescue medication inhalations (puffs) and nebulizer treatments taken will be recorded by the participant in the Asthma Symptom Diary twice daily (i.e., in the morning and evening). Each timepoint is calculated as weekly means based on daily diary data.
Change from baseline in total serum IgE Randomization, Week 52 Mean change from baseline in IgE at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.
Proportion of participants who did not experience an asthma exacerbation Week 52 Percentage of participants who did not experience an asthma exacerbation as compared to placebo at Week 52
Annualized rate of exacerbations associated with emergency room (ER) visit or hospitalizations Randomization to Week 52 Annualized rate of exacerbations associated with ER visit or hospitalization as compared to placebo over 52 weeks
Change from baseline in weekly mean daily Asthma Symptom Diary score Randomization, Week 52 Mean change from baseline in Asthma Symptom Diary score as compared to placebo at Week 52. 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.
Time to first asthma exacerbation Randomization to Week 52 Time to the first occurrence of asthma exacerbation post randomization, presented as number of participants with at least one asthma exacerbation reported in the eCRF
Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) Randomization, Week 52 Mean change from baseline in weekly mean morning and evening peak expiratory flow (PEF) at Week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on other asthma control metrics. Home PEF testing will be performed by the participant in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Each timepoint is calculated as weekly means.
Number of participants with asthma specific resource utilization (e.g.,eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) Randomization to Week 52 Number of participants with asthma specific resource utilization (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks.
European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score Randomization, Week 52 Mean change from baseline in EQ-5D-5L at week 52. EQ-5D-5L has two sections. The first section assesses five dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Patients rate each of these items from "no problem," "slight problem" "moderate problem", "severe problem" and "unable". A composite health index is defined by combining the levels for each dimension. The second section measures self-rated (global) health status using a vertically oriented visual analogue scale where 100 represents the "best possible health state" and 0 represents the "worst possible health state". EQ-5D-5L assesses health status in terms of a single index value or health utility score. It allows "weighting" by the patient of particular health states and the generation of patient utilities. Overall scores range from 0 to 1,with lower scores representing a higher level of dysfunction.
Change from baseline in peripheral blood eosinophils Randomization, Week 52 Mean change from baseline in blood eosinophil counts at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.
Change from baseline in weekly mean number of night time awakenings Randomization, Week 52 Mean change from baseline in weekly mean number of night time awakenings at Week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on other asthma control metrics. Each timepoint is calculated as weekly mean number of awakenings due to asthma based on daily diary data. Weekly mean number of night time awakenings is defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%.
Immunogenicity anti-drug antibodies Baseline to Week 64 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.
Trial Locations
- Locations (1)
Research Site
🇵🇭Quezon City, Philippines