NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma
Bibliographic record
Abstract
BACKGROUND: Patients with severe, uncontrolled asthma have a significant unmet need for new treatments that have broader effects on airway inflammation, and that provide greater improvements in asthma outcomes than currently approved biologics and standard-of-care therapies. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma, irrespective of baseline disease phenotype. This article reports the design and objectives of the pivotal phase 3 NAVIGATOR study. METHODS: NAVIGATOR (NCT03347279) is an ongoing randomized, double-blind, placebo-controlled trial in adults (18-80 years old) and adolescents (12-17 years old) with severe, uncontrolled asthma, who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids (N = 1061). The study population includes approximately equal proportions of patients with high (≥ 300 cells/μL) and low (< 300 cells/μL) blood eosinophil counts. The study comprises a 5-6-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients will receive their prescribed controller medications without change throughout the study. The primary efficacy endpoint is the annualized asthma exacerbation rate during the 52-week treatment period. Key secondary endpoints include the effect of tezepelumab on lung function, asthma control and health-related quality of life. DISCUSSION: NAVIGATOR is evaluating the effect of tezepelumab in patients with a broad range of severe asthma phenotypes at baseline, including those with low blood eosinophil counts. The target sample size for NAVIGATOR (N = 1060) was achieved, and it is the largest clinical study of tezepelumab in severe, uncontrolled asthma to date. NAVIGATOR aims to further investigate the effect of tezepelumab on exacerbations and build on observations from the phase 2b PATHWAY study, and to demonstrate further the potential of tezepelumab to provide patients with severe, uncontrolled asthma with improvements in lung function, asthma control and health-related quality of life. TRIAL REGISTRATION: NCT03347279 (ClinicalTrials.gov). Registered 20 November 2017.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".