Once-Weekly Efanesoctocog Alfa Prophylaxis Provided High Sustained Factor VIII Activity Levels, Independent of Blood Group, in Children <12 Years of Age with Severe Hemophilia A
Notice bibliographique
Résumé
Introduction Efanesoctocog alfa is a new class of factor VIII (FVIII) replacement therapy uniquely designed to overcome the von Willebrand factor-imposed FVIII half-life ceiling. In the Phase 3 XTEND-Kids study in previously treated children <12 years of age with severe hemophilia A, efanesoctocog alfa was well tolerated and FVIII inhibitor development was not detected. Furthermore, once-weekly efanesoctocog alfa 50 IU/kg provided highly effective bleed protection and treatment. These results are consistent with the results of the Phase 3 XTEND-1 study in adolescents and adults with severe hemophilia A. Objective To characterize the pharmacokinetics (PK) of efanesoctocog alfa in children <12 years of age with severe hemophilia A in the XTEND-Kids study (NCT04759131). Methods The XTEND-Kids study enrolled children with severe hemophilia A (<1 IU/dL endogenous FVIII activity) previously treated with FVIII replacement products or cryoprecipitate for ≥150 exposure days (6-<12 years) or ≥50 exposure days (<6 years). Participants received once-weekly efanesoctocog alfa 50 IU/kg for 52 weeks. FVIII activity levels were assessed using the activated partial thromboplastin time-based one-stage clotting assay with the reagent Actin FSL. PK parameters after the first dose were estimated for the 37 participants in the PK subgroup using non-compartmental analysis. Mean peak and trough FVIII activity levels were determined for all participants by visit. Time to FVIII activity levels at steady state (Week 26) was determined using population modelling. Results A total of 74 participants were enrolled in XTEND-Kids; of these, 37 were included in the PK subgroup (n=19, <6 years; n=18, ≥6-<12 years). At the end of the first weekly dosing interval, mean (standard deviation [SD]) FVIII activity levels were 5.73 (1.63) IU/dL in participants <6 years and 6.93 (1.76) IU/dL in those ≥6-<12 years (Figure). After the first dose of efanesoctocog alfa, mean (SD) half-life was 38.0 (3.72) and 42.4 (3.70) hours, and mean (SD) clearance was 0.742 (0.121) and 0.681 (0.139) mL/h/kg in participants <6 years and ≥6-<12 years, respectively (Table). Incremental recovery values remained consistent throughout the study, ranging from 2.12 to 2.35 IU/dL per IU/kg. Mean (SD) areas under the activity-time curve over the dosing interval (AUC 0-tau) were 6800 (1120) and 7190 (1450) h*IU/dL in participants <6 years and ≥6-<12 years, respectively. Mean (SD) clearance after first dose was similar between participants with blood group O and non-O, 0.76 (0.12) versus 0.68 (0.15) mL/h/kg (Table). Half-life was also similar; mean (SD) half-life was 40.2 (4.45) hours in participants with blood group O, and 40.0 (4.17) hours in those with a non-O group. In the overall study population, mean trough (pre-dose) FVIII activity levels ranged from 8.54 IU/dL at Week 4 to 13.7 IU/dL at Week 52. Across all visits mean FVIII activity levels 15 minutes post-dose were consistently below 150 IU/dL. Mean FVIII activity levels at steady state (Week 26) remained >40 IU/dL for 3 days and >10 IU/dL for ~7 days following a 50 IU/kg weekly dose of efanesoctocog alfa. Conclusions PK parameters and the mean FVIII activity-time profile were similar for participants <6 years and ≥6-<12 years of age. No clinically relevant differences in PK parameters were observed between participants with blood group O and non-O. At steady state (Week 26), FVIII activity levels were maintained in the normal to near-normal range (>40 IU/dL) for 3 days and remained >10 IU/dL for ~7 days following a 50 IU/kg dose of efanesoctocog alfa. Once-weekly prophylaxis with efanesoctocog alfa provided high sustained FVIII levels across the week for children <12 years of age in the XTEND-Kids study.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».