Cargando…

Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bar-Or, Amit, Wiendl, Heinz, Montalban, Xavier, Alvarez, Enrique, Davydovskaya, Maria, Delgado, Silvia R, Evdoshenko, Evgeniy P, Giedraitiene, Natasa, Gross-Paju, Katrin, Haldre, Sulev, Herrman, Craig E, Izquierdo, Guillermo, Karelis, Guntis, Leutmezer, Fritz, Mares, Miroslav, Meca-Lallana, Jose E, Mickeviciene, Dalia, Nicholas, Jacqueline, Robertson, Derrick S, Sazonov, Denis V, Sharlin, Kenneth, Sundaram, Bharathy, Totolyan, Natalia, Vachova, Marta, Valis, Martin, Bagger, Morten, Häring, Dieter A, Ludwig, Inga, Willi, Roman, Zalesak, Martin, Su, Wendy, Merschhemke, Martin, Fox, Edward J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024029/
https://www.ncbi.nlm.nih.gov/pubmed/34605319
http://dx.doi.org/10.1177/13524585211044479
_version_ 1784690475038408704
author Bar-Or, Amit
Wiendl, Heinz
Montalban, Xavier
Alvarez, Enrique
Davydovskaya, Maria
Delgado, Silvia R
Evdoshenko, Evgeniy P
Giedraitiene, Natasa
Gross-Paju, Katrin
Haldre, Sulev
Herrman, Craig E
Izquierdo, Guillermo
Karelis, Guntis
Leutmezer, Fritz
Mares, Miroslav
Meca-Lallana, Jose E
Mickeviciene, Dalia
Nicholas, Jacqueline
Robertson, Derrick S
Sazonov, Denis V
Sharlin, Kenneth
Sundaram, Bharathy
Totolyan, Natalia
Vachova, Marta
Valis, Martin
Bagger, Morten
Häring, Dieter A
Ludwig, Inga
Willi, Roman
Zalesak, Martin
Su, Wendy
Merschhemke, Martin
Fox, Edward J
author_facet Bar-Or, Amit
Wiendl, Heinz
Montalban, Xavier
Alvarez, Enrique
Davydovskaya, Maria
Delgado, Silvia R
Evdoshenko, Evgeniy P
Giedraitiene, Natasa
Gross-Paju, Katrin
Haldre, Sulev
Herrman, Craig E
Izquierdo, Guillermo
Karelis, Guntis
Leutmezer, Fritz
Mares, Miroslav
Meca-Lallana, Jose E
Mickeviciene, Dalia
Nicholas, Jacqueline
Robertson, Derrick S
Sazonov, Denis V
Sharlin, Kenneth
Sundaram, Bharathy
Totolyan, Natalia
Vachova, Marta
Valis, Martin
Bagger, Morten
Häring, Dieter A
Ludwig, Inga
Willi, Roman
Zalesak, Martin
Su, Wendy
Merschhemke, Martin
Fox, Edward J
author_sort Bar-Or, Amit
collection PubMed
description 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 (AUC( τ )) and maximum plasma concentration (C(max)) 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 AUC( τ ), 487.7 vs 474.1 h × µg/mL (ratio 1.03); C(max), 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.
format Online
Article
Text
id pubmed-9024029
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-90240292022-04-23 Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study Bar-Or, Amit Wiendl, Heinz Montalban, Xavier Alvarez, Enrique Davydovskaya, Maria Delgado, Silvia R Evdoshenko, Evgeniy P Giedraitiene, Natasa Gross-Paju, Katrin Haldre, Sulev Herrman, Craig E Izquierdo, Guillermo Karelis, Guntis Leutmezer, Fritz Mares, Miroslav Meca-Lallana, Jose E Mickeviciene, Dalia Nicholas, Jacqueline Robertson, Derrick S Sazonov, Denis V Sharlin, Kenneth Sundaram, Bharathy Totolyan, Natalia Vachova, Marta Valis, Martin Bagger, Morten Häring, Dieter A Ludwig, Inga Willi, Roman Zalesak, Martin Su, Wendy Merschhemke, Martin Fox, Edward J Mult Scler Original Research Papers 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 (AUC( τ )) and maximum plasma concentration (C(max)) 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 AUC( τ ), 487.7 vs 474.1 h × µg/mL (ratio 1.03); C(max), 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. SAGE Publications 2021-10-04 2022-05 /pmc/articles/PMC9024029/ /pubmed/34605319 http://dx.doi.org/10.1177/13524585211044479 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Papers
Bar-Or, Amit
Wiendl, Heinz
Montalban, Xavier
Alvarez, Enrique
Davydovskaya, Maria
Delgado, Silvia R
Evdoshenko, Evgeniy P
Giedraitiene, Natasa
Gross-Paju, Katrin
Haldre, Sulev
Herrman, Craig E
Izquierdo, Guillermo
Karelis, Guntis
Leutmezer, Fritz
Mares, Miroslav
Meca-Lallana, Jose E
Mickeviciene, Dalia
Nicholas, Jacqueline
Robertson, Derrick S
Sazonov, Denis V
Sharlin, Kenneth
Sundaram, Bharathy
Totolyan, Natalia
Vachova, Marta
Valis, Martin
Bagger, Morten
Häring, Dieter A
Ludwig, Inga
Willi, Roman
Zalesak, Martin
Su, Wendy
Merschhemke, Martin
Fox, Edward J
Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
title Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
title_full Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
title_fullStr Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
title_full_unstemmed Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
title_short Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
title_sort rapid and sustained b-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: aplios, a randomized phase-2 study
topic Original Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024029/
https://www.ncbi.nlm.nih.gov/pubmed/34605319
http://dx.doi.org/10.1177/13524585211044479
work_keys_str_mv AT baroramit rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT wiendlheinz rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT montalbanxavier rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT alvarezenrique rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT davydovskayamaria rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT delgadosilviar rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT evdoshenkoevgeniyp rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT giedraitienenatasa rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT grosspajukatrin rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT haldresulev rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT herrmancraige rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT izquierdoguillermo rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT karelisguntis rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT leutmezerfritz rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT maresmiroslav rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT mecalallanajosee rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT mickevicienedalia rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT nicholasjacqueline rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT robertsonderricks rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT sazonovdenisv rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT sharlinkenneth rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT sundarambharathy rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT totolyannatalia rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT vachovamarta rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT valismartin rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT baggermorten rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT haringdietera rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT ludwiginga rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT williroman rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT zalesakmartin rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT suwendy rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT merschhemkemartin rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study
AT foxedwardj rapidandsustainedbcelldepletionwithsubcutaneousofatumumabinrelapsingmultiplesclerosisapliosarandomizedphase2study