Long-Term Safety and Effectiveness of Sebetralstat: Interim Analysis of KONFIDENT-S Open-label Extension
Bibliographic record
Abstract
BACKGROUND: Poor compliance with hereditary angioedema guidelines for on-demand treatment is common due to challenges with parenteral administration. Sebetralstat, an oral plasma kallikrein inhibitor, demonstrated faster times to beginning of symptom relief, reduction in attack severity, and complete resolution than placebo in the phase 3 KONFIDENT trial (NCT05259917). OBJECTIVE: This analysis evaluated long-term safety and effectiveness of sebetralstat in KONFIDENT-S (NCT05505916), an ongoing, 2-year, open-label extension study. METHODS: Enrolled participants aged ≥12 years with hereditary angioedema due to C1-inhibitor deficiency administered sebetralstat 600 mg for each attack, as early as possible, regardless of severity or location. The primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes were times to beginning of symptom relief, reduction in severity, and complete resolution. RESULTS: At data cutoff (January 31, 2024), 84 participants (mean age: 35.9 years; 14.3% <18 years; 64.3% female) treated 640 attacks with sebetralstat (84% of total attacks); the median (interquartile range [IQR]) number of attacks per participant was 5 (2-8). The median (IQR) time from attack onset to treatment was 9 (1-69) minutes. Baseline severity was as follows: 30.0% mild, 43.3% moderate, and 25.0% severe or very severe. Treatment-related TEAEs occurred in 8 participants (9.5%); none were serious. The median time to beginning of symptom relief (allowing for missing data entries between consecutive time points) was 1.68 (0.79-3.89) hours, to reduction in severity 6.57 (1.61 to >12) hours, and to complete attack resolution 21.02 (7.22 to >24) hours. No evidence of a diminished response over repeated treatments of attacks was observed. CONCLUSIONS: Oral sebetralstat enabled compliance with treatment guidelines. No new safety signals were observed, and effectiveness for repeated attacks was consistent with the KONFIDENT trial results.
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 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 | 0.018 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 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".