Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.
Mult Scler
; 28(6): 910-924, 2022 05.
Article
in English
| MEDLINE | ID: covidwho-1883453
ABSTRACT
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 101011 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Multiple Sclerosis
Type of study:
Experimental Studies
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Mult Scler
Journal subject:
Neurology
Year:
2022
Document Type:
Article
Affiliation country:
13524585211044479
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