Primary Efficacy Endpoint and Safety Results of Ibalizumab in a Phase 3 Study of Heavily Treatment-Experienced Patients With Multidrug-Resistant Human Immunodeficiency Virus-1 Infection
Notice bibliographique
Résumé
Background. Despite success of combination antiretroviral (ARV) therapy, some patients fail to achieve durable viral suppression due to multidrug-resistant (MDR) human immunodeficiency virus (HIV). Ibalizumab (IBA) is the first long-acting monoclonal antibody HIV-1 entry inhibitor in Phase 3 development for treatment of MDR HIV. IBA was granted Orphan Drug status and Breakthrough Therapy designation by the FDA. Method. TMB-301 is an on-going single arm, 24-week (wk) study of IBA plus optimized background regimen (OBR) in treatment experienced patients with MDR HIV-1. The primary objective was to demonstrate antiviral activity at DAY 14 (7 days after IBA initiation). Patients were monitored for 7 days on a failing ARV regimen (control period). On DAY 7 a 2000-mg IBA loading dose was administered intravenously (IV) as functional monotherapy. The primary efficacy endpoint was the proportion of patients achieving a ≥0.5 log10 decrease in HIV-1 RNA from DAY 7/Baseline (BL) to DAY 14. An OBR with at least one sensitive agent was initiated on DAY 14. IBA was continued at 800 mg IV every two wks for 24 wks on study treatment. Safety and additional efficacy endpoints were evaluated. Result. Forty heavily treatment-experienced patients with MDR HIV were enrolled, mean age of 51 years, 15% female, and 45% non-white. Mean duration of HIV infection was 21 years and 28% were treated with ≥10 previous ARVs. Mean BL CD4+ T-cell count was 161 cells/µL (50% <100 cells/µL) and mean BL viral load (VL) was 5.0 log10 (18% BL VL ≥100,000 copies/mL). Thirty-five percent of patients required an investigational agent in OBR due to extensive resistance. 83% achieved ≥0.5 log10 decrease from BL to DAY 14 on IBA versus 3% during the control period. No treatment-related SAEs or discontinuations were reported during DAY 0–14. End-of-study safety and efficacy assessments are ongoing. Day 14 Intent-to-Treat Results (IBA Added to Stable Failing Regimen) *Protocol deviations affecting analysis: incomplete Day 0 results (n = 1, excluded) and OBR started during control period (n = 1, included). Conclusion. IBA demonstrated statistically significant VL reductions compared to control in MDR HIV patients when added to a failing regimen and was well tolerated. Disclosures. J. Lalezari, TaiMed Biologics USA: Investigator, Research support; W. J. Fessel, TaiMed Biologics USA: Investigator, Research support; S. Schrader, TaiMed Biologics USA: Investigator, Research support; P. Kumar, TaiMed Biologics USA: Investigator, Research support; G. Richmond, TaiMed Biologics USA: Investigator, Research support; C. Marsolais, Theratechnologies Inc: Employee, Salary; S. Weinheimer, TaiMed Biologics USA: Employee, Salary; S. Lewis, TaiMed Biologics USA: Employee, Salary
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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) | 0,001 | 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 | 0,000 |
| 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 ».