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Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
A. Bar-Or, H. Wiendl, X. Montalban, E. Alvarez, M. Davydovskaya, SR. Delgado, EP. Evdoshenko, N. Giedraitiene, K. Gross-Paju, S. Haldre, CE. Herrman, G. Izquierdo, G. Karelis, F. Leutmezer, M. Mares, JE. Meca-Lallana, D. Mickeviciene, J....
Jazyk angličtina Země Velká Británie
Typ dokumentu klinické zkoušky, fáze II, časopisecké články, randomizované kontrolované studie, práce podpořená grantem
- MeSH
- humanizované monoklonální protilátky škodlivé účinky MeSH
- injekce subkutánní MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- roztroušená skleróza * chemicky indukované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × μg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 μg/mL (ratio 1.00)). B-cell counts (median cells/μL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.
Central Texas Neurology Consultants PA Round Rock TX USA
Centre d'Esclerosi Múltiple de Catalunya Hospital Universitari Vall d'Hebron Barcelona Spain
Department of Clinical Trials FSBIH SDMC of FMBA of Russia Novosibirsk Russian Federation
Department of Neurology Medical University of Vienna Vienna Austria
Department of Neurology Pardubice Regional Hospital Pardubice Czech Republic
Department of Neurology Rocky Mountain MS Center University of Colorado Aurora CO USA
Department of Neurology Teplice Hospital Teplice Czech Republic
JWM Neurology Indianapolis IN USA
Lithuanian University of Health Sciences Kaunas Lithuania
MS Center and Department of Neurology Miller School of Medicine University of Miami Miami FL USA
Multiple Sclerosis Unit Hospital Vithas NISA Sevilla Sevilla Spain
Novartis Pharma AG Basel Switzerland
Novartis Pharmaceutical Corporation East Hanover NJ USA
OhioHealth Riverside Methodist Hospital Columbus OH USA
Pirogov Russian National Research Medical University Moscow Russian Federation
Sharlin Health and Neurology Ozark MO USA
Citace poskytuje Crossref.org
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