Cargando…

Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis

OBJECTIVES: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. METHODS: In this 20-week, randomized...

Descripción completa

Detalles Bibliográficos
Autores principales: Constantinescu, Cris S., Asher, Aliya, Fryze, Waldemar, Kozubski, Wojciech, Wagner, Frank, Aram, Jehan, Tanasescu, Radu, Korolkiewicz, Roman P., Dirnberger-Hertweck, Maren, Steidl, Stefan, Libretto, Susan E., Sprenger, Till, Radue, Ernst W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442097/
https://www.ncbi.nlm.nih.gov/pubmed/26185773
http://dx.doi.org/10.1212/NXI.0000000000000117
_version_ 1782372856804409344
author Constantinescu, Cris S.
Asher, Aliya
Fryze, Waldemar
Kozubski, Wojciech
Wagner, Frank
Aram, Jehan
Tanasescu, Radu
Korolkiewicz, Roman P.
Dirnberger-Hertweck, Maren
Steidl, Stefan
Libretto, Susan E.
Sprenger, Till
Radue, Ernst W.
author_facet Constantinescu, Cris S.
Asher, Aliya
Fryze, Waldemar
Kozubski, Wojciech
Wagner, Frank
Aram, Jehan
Tanasescu, Radu
Korolkiewicz, Roman P.
Dirnberger-Hertweck, Maren
Steidl, Stefan
Libretto, Susan E.
Sprenger, Till
Radue, Ernst W.
author_sort Constantinescu, Cris S.
collection PubMed
description OBJECTIVES: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. METHODS: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. RESULTS: Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. CONCLUSIONS: MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. CLASSIFICATION OF EVIDENCE: This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS.
format Online
Article
Text
id pubmed-4442097
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-44420972015-07-16 Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis Constantinescu, Cris S. Asher, Aliya Fryze, Waldemar Kozubski, Wojciech Wagner, Frank Aram, Jehan Tanasescu, Radu Korolkiewicz, Roman P. Dirnberger-Hertweck, Maren Steidl, Stefan Libretto, Susan E. Sprenger, Till Radue, Ernst W. Neurol Neuroimmunol Neuroinflamm Article OBJECTIVES: To determine the safety, pharmacokinetics (PK), and immunogenicity of the recombinant human monoclonal antibody MOR103 to granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with multiple sclerosis (MS) with clinical or MRI activity. METHODS: In this 20-week, randomized, double-blind, placebo-controlled phase 1b dose-escalation trial (registration number NCT01517282), adults with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) received an IV infusion of placebo (n = 6) or MOR103 0.5 (n = 8), 1.0 (n = 8), or 2.0 (n = 9) mg/kg every 2 weeks for 10 weeks. Patients had to have ≤10 gadolinium (Gd)-enhancing brain lesions on T1-weighted MRI at baseline. The primary objective was safety. RESULTS: Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most frequent was nasopharyngitis. Between-group differences in TEAE numbers were small. There were no TEAE-related trial discontinuations, infusion-related reactions, or deaths. Nine patients experienced MS exacerbations: 3, 5, 1, and 0 patient(s) in the placebo, 0.5, 1.0, and 2.0 mg/kg groups, respectively. A few T1 Gd-enhancing lesions and/or new or enlarging T2 lesions indicative of inflammation were observed in all treatment groups. No clinically significant changes were observed in other clinical assessments or laboratory safety assessments. No anti-MOR103 antibodies were detected. PK evaluations indicated dose linearity with low/no drug accumulation over time. CONCLUSIONS: MOR103 was generally well-tolerated in patients with RRMS or SPMS. No evidence of immunogenicity was found. CLASSIFICATION OF EVIDENCE: This phase 1b study provides Class I evidence that MOR103 has acceptable tolerability in patients with MS. Lippincott Williams & Wilkins 2015-05-21 /pmc/articles/PMC4442097/ /pubmed/26185773 http://dx.doi.org/10.1212/NXI.0000000000000117 Text en © 2015 American Academy of Neurology This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 4.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Article
Constantinescu, Cris S.
Asher, Aliya
Fryze, Waldemar
Kozubski, Wojciech
Wagner, Frank
Aram, Jehan
Tanasescu, Radu
Korolkiewicz, Roman P.
Dirnberger-Hertweck, Maren
Steidl, Stefan
Libretto, Susan E.
Sprenger, Till
Radue, Ernst W.
Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
title Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
title_full Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
title_fullStr Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
title_full_unstemmed Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
title_short Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis
title_sort randomized phase 1b trial of mor103, a human antibody to gm-csf, in multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442097/
https://www.ncbi.nlm.nih.gov/pubmed/26185773
http://dx.doi.org/10.1212/NXI.0000000000000117
work_keys_str_mv AT constantinescucriss randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT asheraliya randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT fryzewaldemar randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT kozubskiwojciech randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT wagnerfrank randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT aramjehan randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT tanasescuradu randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT korolkiewiczromanp randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT dirnbergerhertweckmaren randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT steidlstefan randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT librettosusane randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT sprengertill randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis
AT radueernstw randomizedphase1btrialofmor103ahumanantibodytogmcsfinmultiplesclerosis