A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis
| Autor: | Sean A. Power, Richard Shubin, Matthew Gormley, Amy E. Lovett-Racke, Edward Fox, Sibyl Wray, Maria Petracca, Koby Mok, Yue Liu, Matilde Inglese, Jenna A. Bosco, Michael S Weiss, Sirio Cocozza |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
TG-1101
medicine.drug_class Ublituximab multiple sclerosis Monoclonal antibody Epitope gadolinium-enhancing lesions magnetic resonance imaging relapse 03 medical and health sciences Multiple Sclerosis Relapsing-Remitting 0302 clinical medicine Antigen Recurrence medicine Humans In patient Anti cd20 030304 developmental biology CD20 0303 health sciences biology business.industry Multiple sclerosis Antibodies Monoclonal Antigens CD20 medicine.disease Neurology Cancer research biology.protein Neurology (clinical) business Original Research Papers 030217 neurology & neurosurgery |
| Zdroj: | Multiple Sclerosis (Houndmills, Basingstoke, England) |
| ISSN: | 1477-0970 1352-4585 |
| DOI: | 10.1177/1352458520918375 |
| Popis: | Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1–4 hours on day 1 and 450–600 mg over 1–3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts ( N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1–2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( p = 0.003) and a 10.6% decrease in T2 lesion volume ( p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|