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APATURA: a Phase 2a study of elarekibep, an inhaled IL-4 receptor alpha inhibitor, in moderate-to-severe asthma

2024· article· en· W4404100045 on OpenAlexaff
Tania Hugo, Andrew R. Harper, Jacob Leander, P. Lundin, David Bock, Xiaohong Zhou, Irina Bondarenko, Steve Burns, Erol Wiegert, Mary F. Fitzgerald, D. Close, David J. Keeling, Hitesh Pandya, Maria G. Belvisi, Paul M. O’Byrne

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicAsthma and respiratory diseases
Canadian institutionsMcMaster University
Fundersnot available
KeywordsAsthmaAlpha (finance)MedicinePharmacologyInternal medicineAnesthesiaSurgery

Abstract

fetched live from OpenAlex

Background: Elarekibep (AZD1402/PRS-060) is an inhaled Anticalin® protein engineered to inhibit IL-4 receptor alpha signaling, a clinically validated asthma target. Methods: A two-part Phase 2a randomized, double-blind, placebo-controlled, dose ranging study in adults ( NCT04643158 ). Part 1 evaluated safety and PK following 28 days twice daily dosing with dry powder formulated elarekibep (1, 3, 10mg) or placebo in controlled patients (ACQ-6 ≤ 1.0) on a stable medium ICS-LABA dose. Part 2 evaluated efficacy of elarekibep (1, 3mg) versus placebo following twice daily dosing for 28 days in a T2-high, uncontrolled moderate-severe asthma population. Results: 72 patients randomized (Part 1: n=50; Part 2: n=22). No clinical safety concerns were reported; the study was stopped early due to new non-clinical findings. Treatment-emergent adverse events were reported for 56.0% (elarekibep, 58.8%; placebo, 50.0%) of patients in Part 1 and 63.6% (elarekibep, 61.5 %; placebo, 66.7%) in Part 2. One SAE, in the 3mg group, was reported during follow up. After inhalation, elarekibep was steadily absorbed (Tmax 3-4 hours) with an elimination half-life ranging between 8-20 hours. Treatment emergent ADAs were detected in 83% (n= 38/46) of elarekibep exposed individuals with no impact on PK characteristics. At Week 4, the LS mean increase (95% CI) in prebronchodilator FEV1 of the 3mg elarekibep group was 196ml (14.3; 378) compared to placebo. Conclusions: Elarekibep was clinically well-tolerated with no identified short-term safety concerns. Due to early study termination, firm conclusions about efficacy could not be drawn. Clinical development has been discontinued due to pre-clinical findings.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0020.001
Open science0.0010.000
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0080.002

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.

Opus teacher head0.019
GPT teacher head0.323
Teacher spread0.304 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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