PB2304 CRIZANLIZUMAB DOSE CONFIRMATION IN PEDIATRIC PATIENTS WITH SICKLE CELL DISEASE: SOLACE‐KIDS TRIAL DESIGN
Notice bibliographique
Résumé
Background: Sickle cell disease (SCD) is the most common serious single‐gene disorder in the world and can lead to complications, including acute pain and acute/chronic organ damage. Episodes of vaso‐occlusion are a hallmark of SCD. P‐selectin, an adhesion molecule expressed primarily on endothelial cells and platelets, plays a key role in the initiation of leukocyte rolling along the blood vessel wall (leading to inflammation propagation) and contributes to multicellular adhesion and microvascular occlusion in SCD. Although children and adults with SCD have similar P‐selectin expression, SCD worsens with advancing age as repeated vascular occlusion results in cumulative endothelial damage. Crizanlizumab, a humanized monoclonal antibody that binds P‐selectin and blocks interaction with its ligands (including leukocyte PSGL‐1), significantly decreased vaso‐occlusive crises (VOCs) leading to healthcare visit vs placebo and was well tolerated in SUSTAIN, a phase 2 study in adults with SCD. Aims: To report the design of the first crizanlizumab study in pediatric patients with SCD. Methods: Primary objectives of this phase 2, multicenter, open‐label study are to confirm appropriate dosing and safety of crizanlizumab therapy in patients >6mo – <18yrs, using sequential, descending age groups of pediatric SCD patients. Secondary objectives include assessing number of VOCs and number/duration of hospitalizations and emergency room visits. Planned enrollment is ≥100 patients with confirmed SCD diagnosis (all genotypes), who experienced ≥1 VOC within the preceding 12mo, in 3 sequential descending age groups: Group 1 (≥26 patients; 12yr‐<18yr), Group 2 (≥26 patients; 6yr – <12yr), and Group 3 (≥8 patients; 2yr – <6yr) and (≥6 patients; 6mo – <2yr). First, the dose will be confirmed (Part A) by ≥8 patients in Group 1. If not confirmed, the dose will be adjusted based on observed pharmacokinetics/pharmacodynamics, and ≥8 additional patients will be enrolled in Group 1 (Part A) to confirm the new dose. Once the dose is confirmed, Group 1 will be expanded (Part B), and ≥8 patients will be enrolled to Group 2 for dose confirmation. This schema will continue until dose confirmed in Group 3, which will then be expanded for enrollment of an exploratory group of ≥6 patients ages 6mo‐<24mo. Patients being treated with hydroxyurea/hydroxycarbamide must have been taking it for ≥6mo prior to study entry with no planned dose adjustments other than accounting for weight changes. Crizanlizumab (5.0 mg/kg intravenously) will be administered on week 1, week 3, and every 4 weeks thereafter for 2 years. Results: Trial ongoing (ClinicalTrials.gov: NCT03474965). Summary/Conclusion: This study aims to address the unmet treatment need in pediatric patients with SCD by establishing pharmacokinetics/pharmacodynamics and confirming appropriate dose in different age groups. Safety will be assessed as a primary objective. Additionally, the number of VOCs and number/duration of hospitalizations and emergency room visits will be assessed as a secondary objective. Sponsored by Novartis.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 tête enseignante, 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 ».