Phase 1/2 Clinical Study of VRDN-001, A Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R), in Patients with Thyroid Eye Disease (TED) (P3-9.001)
Notice bibliographique
Résumé
Objective: Report results from the first cohort of TED patients treated with 2 intravenous infusions of 10 mg/kg VRDN-001 from our phase 1/2 double-masked randomized clinical trial (NCT05176639). Background: IGF-1R antagonism can reduce TED-related inflammation and proptosis. We are evaluating VRDN-001, a full antagonist antibody to IGF-1R, in TED patients at doses of 3, 10, and 20 mg/kg. Design/Methods: Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 intravenous infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy were assessed. Endpoints included overall responder rate (% of subjects with ≥2 mm reduction in proptosis and ≥2 points reduction in CAS), proptosis responder rate (% of subjects with ≥2 mm improvement), change from baseline in proptosis and CAS, proportion of subjects 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, 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). Proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo) and CAS decreased by 4.3 (VRDN-001) vs. 1.5 (placebo). CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). One case of transient hearing impairment that resolved by next visit, with normal audiometry, was reported. No serious AEs, hyperglycemia, or infusion reactions occurred. Conclusions: Two infusions of 10 mg/kg VRDN-001 led to rapid, substantial improvement across all efficacy measures at 6 weeks in TED patients, surpassing 6-week results from 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. Disclosure: Dr. Moster has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Gensight . Dr. Moster has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian. Dr. Moster has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Kilcoyne and Nesbitt. Dr. Douglas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Douglas has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Douglas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon Therapeutics. Dr. Cockerham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Dr. Cockerham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian Pharmaceuticals. Dr. Cockerham has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon therapeutics. Dr. Cockerham has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Horizon Therapeutics. Dr. Cockerham has received research support from Viridian Pharmaceuticals. Dr. Turbin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. The institution of Dr. Turbin has received research support from Viridian. Dr. Nijhawan has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for College of Physicians and Surgeons of Ontario. Dr. Nijhawan has received research support from Viridian Therapeutics. The institution of Dr. Schiffman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Schiffman has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for lAW FIRMS. Dr. Schiffman has received intellectual property interests from a discovery or technology relating to health care. Dr. Ugradar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian Therapeutics. Dr. Ugradar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Valenza Bio. Dr. Oshaughnessy has received personal compensation for serving as an employee of viridian therapeutics. Dr. Oshaughnessy has stock in viridian therapeutics. Mrs. Summerfelt has received personal compensation for serving as an employee of Viridian Therapeutics. An immediate family member of Mrs. Summerfelt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Viridian Therapeutics. Mrs. Summerfelt has stock in Viridian Therapeutics. Dr. She has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. She has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus Therapeutics. Dr. She has stock in Viridian Therapeutics. Dr. Katz has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Katz has received stock or an ownership interest from Viridian Therapeutics.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».