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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03347279
• Date of registration: 09/11/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma NAVIGATOR
• Scientific title: 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 (NAVIGATOR)
• Date of first enrolment: November 23, 2017
• Target sample size: 1061
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03347279
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, France, Germany, Israel, Japan, Korea, Republic of, Russian Federation, Saudi Arabia, South Africa, Taiwan, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Andrew Menzies-Gow, MD
• Affiliation: Royal Brompton Hospital, United Kingdom

Key inclusion & exclusion criteria

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.



Age minimum: 12 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Biological: Experimental: Tezepelumab

Other: Placebo

Primary Outcome(s)

Annualized asthma exacerbation rate (AERR) [Time Frame: Baseline to Week 52]

Secondary Outcome(s)

Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(S)+12) total score [Time Frame: Baseline, Week 52]

Asthma specific resource utilization (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) [Time Frame: Baseline, Week 52]

Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) [Time Frame: Baseline, Week 52]

Annualized rate of exacerbations associated with emergency room visit, urgent care visit, or hospitalization [Time Frame: Baseline to Week 52]

Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) Score [Time Frame: Baseline, Week 52]

Change from baseline in pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) [Time Frame: Baseline, Week 52]

Change from baseline in total serum IgE [Time Frame: Baseline, Week 52]

Change from baseline in weekly mean daily Asthma Symptom Diary score [Time Frame: Baseline, Week 52]

Proportion of subjects who did not experience an asthma exacerbation [Time Frame: Baseline to Week 52]

Serum trough concentrations [Time Frame: Baseline to Week 52]

Work Productivity and Activity Impairment (WPAI+CIQ) Questionnaire and Classroom Impairment Questionnaire score [Time Frame: Week 52]

Change from baseline in weekly mean rescue medication use [Time Frame: Baseline, Week 52]

Immunogenicity anti-drug antibodies [Time Frame: Baseline to Week 52]

Change from baseline in fractional exhaled nitric oxide FENO (ppb) at clinic [Time Frame: Baseline, Week 52]

Change from baseline in peripheral blood eosinophils [Time Frame: Baseline, Week 52]

Change from baseline in weekly mean number of night time awakenings [Time Frame: Baseline, Week 52]

European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score [Time Frame: Week 52]

Patient Global Impression of Change/Severity (PGI-C, PGI-S) and Clinician Global Impression of Change (CGI-C) [Time Frame: Week 52]

Time to first asthma exacerbation [Time Frame: Baseline to Week 52]

Secondary ID(s)

D5180C00007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Amgen