FRI545 Durability Of Treatment Response With VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor, In Patients With Thyroid Eye Disease (TED): Phase 1/2 Clinical Study
Notice bibliographique
Résumé
Abstract Disclosure: R. Douglas: Consulting Fee; Self; Horizon Therapeutics, Viridian Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc., Horizon Therapeutics. S. Ugradar: Consulting Fee; Self; Viridian Therapeutics Inc. K. Cockerham: Advisory Board Member; Self; Viridian Therapeutics Inc., Horizon Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc. Speaker; Self; Horizon Therapeutics. R.E. Turbin: Advisory Board Member; Self; Horizon Therapeutics. Research Investigator; Self; Viridian Therapeutics Inc. Stock Owner; Self; Viridian Therapeutics Inc. R. Tang: Consulting Fee; Self; Viridian Therapeutics Inc. Research Investigator; Self; Viridian Therapeutics Inc., Horizon Therapeutics. N. Nijhawan: Research Investigator; Self; Viridian Therapeutics Inc. D.J. O’Shaughnessy: Employee; Self; Viridian Therapeutics Inc. R.M. Summerfelt: Employee; Self; Viridian Therapeutics Inc. A. She: Employee; Self; Viridian Therapeutics Inc. B. Katz: Employee; Self; Viridian Therapeutics Inc. Introduction: Clinical and preclinical evidence demonstrate IGF-1 receptor (IGF-1R) antagonism reduces TED-related inflammation and proptosis. VRDN-001, a subnanomolar affinity, full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 double-masked RCT (NCT05176639) at 3, 10, or 20 mg/kg administered intravenously. Results from the first cohort of TED patients (10 mg/kg) are presented here. Methods: Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy through 12 weeks were assessed. Endpoints included overall responder rate (% of patients with ≥2 mm reduction in proptosis and ≥2 point reduction in CAS), proptosis responder rate (% of patients with ≥2 mm reduction), change from baseline in proptosis and CAS, proportion of patients with CAS decrease to 0 or 1, and diplopia resolution. Results: Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). After 2 infusions, at 6 weeks, the overall responder rate was 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). Proptosis responder rate was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). Mean proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo). MRI analysis of proptosis, available for 4 of 6 drug-treated patients, confirmed proptosis improvement in each; MRI analysis showed slight worsening of proptosis in both placebo patients. CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo), with mean decreases of 4.3 (VRDN-001) and 1.5 (placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). Durability of response in the 5 VRDN-001 treatment responders at 6 weeks persisted through 12 weeks: 80% (4/5) maintained overall responder status and 80% (4/5) maintained proptosis responder status, with mean reduction in proptosis at week 12 of 2.2 mm for all 6 drug-treated patients; MRI analysis confirmed the maintained response for all 4 of the drug-treated patients for whom scans were available. Mean CAS reduction remained consistent (4.2 at Week 12 vs. 4.3 at Week 6) and 80% (4/5) maintained a CAS of 0 or 1. All 4 patients with baseline diplopia had diplopia resolution at Week 12. VRDN-001 was well-tolerated through 12 weeks. AEs were mostly mild, with no severe or serious AEs reported. Conclusions: Two infusions of 10 mg/kg VRDN-001 were well tolerated in this cohort of TED patients, and the rapid, clinically meaningful improvement across all efficacy measures by 6 weeks was sustained through 12 weeks. Further, these results were achieved with a lower dose and fewer treatments than in prior RCTs of other anti-IGF-1R antibodies. Results from the additional 3 mg/kg and 20 mg/kg cohorts may extend these findings and define potential VRDN-001 treatment regimens. Presentation: Friday, June 16, 2023
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».