A FIRST-IN-HUMAN PHASE 1/2A CLINICAL STUDY OF ICM-203 AAV GENE THERAPY: PROMISING SIGNALS AS A DMOAD CANDIDATE
Notice bibliographique
Résumé
INTRODUCTION ICM-203, a recombinant AAV vector designed to express a truncated form of human Nkx3.2, a transcription factor which plays an important role in both chondrocyte and synoviocyte activity, is in clinical development as a potential DMOAD. OBJECTIVE An unblinded interim analysis of the low dose cohort of the first-in-human phase 1/2a study of ICM-203 was conducted to assess the safety, immunogenicity, and biological activity of ICM-203. METHODS In the low dose cohort of this phase 1/2a, double-blind, placebo-controlled, dose escalation study (NCT04875754), 8 subjects with Kellgren-Lawrence grade 3 osteoarthritis (OA) of the knee were randomized to receive a single intra-articular injection of ICM-203 or placebo in a 3:1 ratio. The primary safety endpoint was safety and tolerability of ICM-203 through assessment of treatment-emergent adverse events (TEAEs). Immunogenicity endpoints included measuring serum neutralizing antibody (NAb) titers and T-cell responses to ICM-203’s AAV capsid. As efficacy endpoints, changes in knee pain and function were assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale and KOOS activities of daily living (ADL) subscale, respectively; these KOOS scores were converted to calculate Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Imaging endpoints included Magnetic Resonance Imaging (MRI) Osteoarthritis Knee Scores (MOAKS) focusing on bone marrow lesions (BML), synovitis, articular cartilage damage, and osteophytes. RESULTS Of 11 screened subjects, 8 qualified and received a single intra-articular injection of ICM-203 (N=6) or placebo (N=2); all subjects completed 52 weeks of follow-up. Subject age ranged from 56 to 73 years; body mass index (BMI) ranged from 24.6 to 38.6 kg/m2. No significant concerns about safety or tolerability arose. The most common treatment-related TEAE was mild to moderate arthralgia, which occurred in 3 of 6 ICM-203 subjects and 1 of 2 placebo subjects. At baseline, 3 ICM-203 subjects had positive NAb responses to AAV capsid; no subjects had significant T-cell responses. All 6 ICM-203 subjects developed both a humoral and cellular response against AAV capsid, whereas neither placebo subject did. ICM-203 subjects with negative NAb at baseline (N=3) demonstrated greater improvement over placebo subjects (N=2) in KOOS pain, KOOS ADL, WOMAC, as well as in imaging endpoints, including MOAKS BML and synovitis. For articular cartilage and osteophytes, no significant changes were observed in any subject between baseline and week 52. CONCLUSION Intra-articular injections of ICM-203 were safe and well tolerated. ICM-203 appeared to show greater therapeutic activity over placebo in subjects with negative NAb at baseline. Current findings indicate ICM-203 may demonstrate potential as a disease-modifying osteoarthritis drug (DMOAD), between reducing osteoarthritis symptoms, ameliorating structural joint damage, and alleviating synovial inflammation. Investigation of higher doses of ICM-203 is in progress.
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 | 0,001 | 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) | 0,000 | 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 ».