The effects of a <scp>CCR</scp>3 inhibitor, <scp>AXP</scp>1275, on allergen‐induced airway responses in adults with mild‐to‐moderate atopic asthma
Bibliographic record
Abstract
Summary Background CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. Objective This proof‐of‐mechanism study examined the effect of AXP1275, an oral, small‐molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. Methods Twenty‐one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double‐blind cross‐over study to compare early and late allergen‐induced asthmatic responses, methacholine PC20, blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once‐daily doses of AXP1275 (50 mg) or placebo. Results There was a significant increase in methacholine PC20 after 12 days of AXP1275 treatment compared to placebo (increase of 0.92 doubling doses versus 0.17 doubling doses, P = .01), but this protection was lost post‐allergen challenge. There was no effect of AXP1275 on allergen‐induced late asthmatic responses, or eosinophils in blood and sputum. The early asthmatic response and exhaled nitric oxide levels were slightly lower with AXP1275, but this did not reach statistical significance. The number of subjects who experienced treatment‐emergent adverse events while receiving AXP1275 was comparable placebo. Conclusions & Clinical Relevance AXP1275 50 mg administered daily was safe and well tolerated, and there was no difference in the type, severity or frequency of treatment‐emergent adverse events in subjects while receiving AXP1275 compared to placebo. AXP1275 increased the methacholine PC20; however, the low and variable exposure to APX1275 over a short treatment period may have contributed to poor efficacy on other outcomes.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".