MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

Frank Behrens; Paul P Tak; Mikkel Ostergaard; Rumen Stoilov; Piotr Wiland; Thomas W Huizinga; Vadym Y Berenfus; Stoyanka Vladeva; Juergen Rech; Andrea Rubbert-Roth; Mariusz Korkosz; Dmitriy Rekalov; Igor A Zupanets; Bo J Ejbjerg; Jens Geiseler; Julia Fresenius; Roman P Korolkiewicz; Arndt J Schottelius; Harald Burkhardt

doi:10.1136/annrheumdis-2013-204816

MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

Frank Behrens, Paul P Tak, Mikkel Ostergaard, Rumen Stoilov, Piotr Wiland, Thomas W Huizinga, Vadym Y Berenfus, Stoyanka Vladeva, Juergen Rech, Andrea Rubbert-Roth, Mariusz Korkosz, Dmitriy Rekalov, Igor A Zupanets, Bo J Ejbjerg, Jens Geiseler, Julia Fresenius, Roman P Korolkiewicz, Arndt J Schottelius, Harald Burkhardt

Institut for Klinisk Medicin

89 Citationer (Scopus)

Abstract

OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA).

METHODS: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety.

RESULTS: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters.

CONCLUSIONS: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases.

TRIAL REGISTRATION NUMBER: NCT01023256.

Originalsprog	Engelsk
Tidsskrift	Annals of the Rheumatic Diseases
Vol/bind	74
Udgave nummer	6
Sider (fra-til)	1058-1064
Antal sider	7
ISSN	0003-4967
DOI	https://doi.org/10.1136/annrheumdis-2013-204816
Status	Udgivet - 1 jun. 2015

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Citationsformater

Behrens, F., Tak, P. P., Ostergaard, M., Stoilov, R., Wiland, P., Huizinga, T. W., Berenfus, V. Y., Vladeva, S., Rech, J., Rubbert-Roth, A., Korkosz, M., Rekalov, D., Zupanets, I. A., Ejbjerg, B. J., Geiseler, J., Fresenius, J., Korolkiewicz, R. P., Schottelius, A. J., & Burkhardt, H. (2015). MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Annals of the Rheumatic Diseases, 74(6), 1058-1064. https://doi.org/10.1136/annrheumdis-2013-204816

MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis : results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. / Behrens, Frank; Tak, Paul P; Ostergaard, Mikkel et al.

I: Annals of the Rheumatic Diseases, Bind 74, Nr. 6, 01.06.2015, s. 1058-1064.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Behrens, F, Tak, PP, Ostergaard, M, Stoilov, R, Wiland, P, Huizinga, TW, Berenfus, VY, Vladeva, S, Rech, J, Rubbert-Roth, A, Korkosz, M, Rekalov, D, Zupanets, IA, Ejbjerg, BJ, Geiseler, J, Fresenius, J, Korolkiewicz, RP, Schottelius, AJ & Burkhardt, H 2015, 'MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial', Annals of the Rheumatic Diseases, bind 74, nr. 6, s. 1058-1064. https://doi.org/10.1136/annrheumdis-2013-204816

Behrens F, Tak PP, Ostergaard M, Stoilov R, Wiland P, Huizinga TW et al. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Annals of the Rheumatic Diseases. 2015 jun. 1;74(6):1058-1064. doi: 10.1136/annrheumdis-2013-204816

Behrens, Frank ; Tak, Paul P ; Ostergaard, Mikkel et al. / MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis : results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. I: Annals of the Rheumatic Diseases. 2015 ; Bind 74, Nr. 6. s. 1058-1064.

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title = "MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial",

abstract = "OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA).METHODS: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety.RESULTS: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters.CONCLUSIONS: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases.TRIAL REGISTRATION NUMBER: NCT01023256.",

author = "Frank Behrens and Tak, {Paul P} and Mikkel Ostergaard and Rumen Stoilov and Piotr Wiland and Huizinga, {Thomas W} and Berenfus, {Vadym Y} and Stoyanka Vladeva and Juergen Rech and Andrea Rubbert-Roth and Mariusz Korkosz and Dmitriy Rekalov and Zupanets, {Igor A} and Ejbjerg, {Bo J} and Jens Geiseler and Julia Fresenius and Korolkiewicz, {Roman P} and Schottelius, {Arndt J} and Harald Burkhardt",

year = "2015",

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doi = "10.1136/annrheumdis-2013-204816",

language = "English",

volume = "74",

pages = "1058--1064",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

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TY - JOUR

T1 - MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis

T2 - results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

AU - Behrens, Frank

AU - Tak, Paul P

AU - Ostergaard, Mikkel

AU - Stoilov, Rumen

AU - Wiland, Piotr

AU - Huizinga, Thomas W

AU - Berenfus, Vadym Y

AU - Vladeva, Stoyanka

AU - Rech, Juergen

AU - Rubbert-Roth, Andrea

AU - Korkosz, Mariusz

AU - Rekalov, Dmitriy

AU - Zupanets, Igor A

AU - Ejbjerg, Bo J

AU - Geiseler, Jens

AU - Fresenius, Julia

AU - Korolkiewicz, Roman P

AU - Schottelius, Arndt J

AU - Burkhardt, Harald

PY - 2015/6/1

Y1 - 2015/6/1

N2 - OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA).METHODS: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety.RESULTS: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters.CONCLUSIONS: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases.TRIAL REGISTRATION NUMBER: NCT01023256.

AB - OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA).METHODS: Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety.RESULTS: Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters.CONCLUSIONS: MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases.TRIAL REGISTRATION NUMBER: NCT01023256.

U2 - 10.1136/annrheumdis-2013-204816

DO - 10.1136/annrheumdis-2013-204816

M3 - Journal article

C2 - 24534756

SN - 0003-4967

VL - 74

SP - 1058

EP - 1064

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 6

ER -