Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years
Bibliographic record
Abstract
Background Hereditary angioedema (HAE) is a rare genetic disorder with symptoms often appearing during childhood. Current approved long-term prophylaxis (LTP) for children aged <12 years requires parenteral administration. Berotralstat is an oral, small-molecule plasma kallikrein inhibitor, approved as prophylaxis of HAE attacks in patients aged 12 years or older. Objective To evaluate oral berotralstat for the LTP of HAE in pediatric patients through APeX-P (NCT05453968), the largest trial of LTP in patients with HAE aged 2 to <12 years. Methods Before berotralstat initiation, patients received standard of care for 12 weeks. Pharmacokinetics, safety, and efficacy of berotralstat were assessed in a planned interim analysis. Results Median (range) age of patients (N = 29) was 8.0 (3-11) years, with 48.3% female. Median age at symptom onset was 2.0 years, and 82.8% of patients reported symptom onset before 6 years. Steady-state berotralstat median (range) T max was 3.9 (0.9-6.0) hours, geometric mean (coefficient of variation) C max was 204 ng/mL (40%), and AUC 0-last was 915 ng•h/mL (42%). Most common treatment-emergent adverse events (AEs) were nasopharyngitis, upper respiratory tract infection, and headache. There were no drug-related grade 3/4 or serious AEs, deaths, or discontinuations related to AEs. Median (range) HAE attack rate during standard of care was 0.96 (0-5.0) attacks per 4-week period. Median (range) HAE attack rates for each 4-week period from day 1 to week 48 were 0 (week 4: 0-4.0; week 48: 0-1.7). Conclusion Oral berotralstat was well tolerated and resulted in early and sustained reductions in HAE attack rates. Trial Registration ClinicalTrials.gov Identifier: NCT05453968 and ClinicalTrialsRegister.eu Identifier: EU CTN 2024-511257-22-00.
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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 | 0.000 | 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 | 0.000 | 0.000 |
| 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".