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 CCR 3 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 AXP 1275, an oral, small‐molecule inhibitor of CCR 3, 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 PC 20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once‐daily doses of AXP 1275 (50 mg) or placebo. Results There was a significant increase in methacholine PC 20 after 12 days of AXP 1275 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 AXP 1275 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 AXP 1275, but this did not reach statistical significance. The number of subjects who experienced treatment‐emergent adverse events while receiving AXP 1275 was comparable placebo. Conclusions & Clinical Relevance AXP 1275 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 AXP 1275 compared to placebo. AXP 1275 increased the methacholine PC 20 ; however, the low and variable exposure to APX 1275 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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".