A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients

Multiple Sclerosis

Volumn 21, Issue 7, 2015, Pages 885-893

  Derfuss, Tobias ^b   Curtin, François ^a   Guebelin, Claudia ^b   Bridel, Claire ^c   Rasenack, Maria ^b   Matthey, Alain ^c   Du Pasquier, Renaud ^d   Schluep, Myriam ^d   Desmeules, Jules ^c   Lang, Alois B ^a   Perron, Hervé ^a   Faucard, Raphael ^a   Porchet, Hervé ^a,e   Hartung, Hans Peter ^f   Kappos, Ludwig ^b   Lalive, Patrice H ^c,g  

^a GENEURO SA   (Switzerland)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

^c GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^d LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^e UNIVERSITY OF PRETORIA   (South Africa)

^f HEINRICH HEINE UNIVERSITY   (Germany)

^g UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

clinical trial; endogenous retrovirus; human endogenous retrovirus type W family; monoclonal antibody; Multiple sclerosis; multiple sclerosis associated retrovirus

Indexed keywords

DRUG ANTIBODY; GAMMA GLUTAMYLTRANSFERASE; GAMMA INTERFERON; INTERLEUKIN 6; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY GNBAC1; PLACEBO; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN; VIRUS RNA; GNBAC1 MONOCLONAL ANTIBODY;

ADULT; AREA UNDER THE CURVE; ARTICLE; BRAIN DAMAGE; CLINICAL ARTICLE; CONTROLLED STUDY; CYSTITIS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; ENDOGENOUS RETROVIRUS; FATIGUE; FEMALE; GAIT DISORDER; GENE EXPRESSION; HEADACHE; HUMAN; HUMAN CELL; HYPERGLYCEMIA; IMMUNOGENICITY; LEUKOCYTURIA; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; MIDDLE AGED; MULTICENTER STUDY; MULTIPLE SCLEROSIS; MULTIPLE SCLEROSIS ASSOCIATED RETROVIRUS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OPEN STUDY; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PROTEIN BLOOD LEVEL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; REPEATED DRUG DOSE; RHINITIS; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE; SINUS BRADYCARDIA; THORAX PAIN; TIME TO MAXIMUM PLASMA CONCENTRATION; VIRUS TRANSCRIPTION; ANTAGONISTS AND INHIBITORS; BRAIN; CLINICAL TRIAL; PATHOLOGY; POLYMERASE CHAIN REACTION; VIROLOGY;

ADULT; ANTIBODIES, MONOCLONAL, HUMANIZED; BRAIN; DOUBLE-BLIND METHOD; ENDOGENOUS RETROVIRUSES; FEMALE; GENE PRODUCTS, ENV; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; MULTIPLE SCLEROSIS; POLYMERASE CHAIN REACTION; RNA, VIRAL;

EID: 84930408517     PISSN: 13524585     EISSN: 14770970     Source Type: Journal    
DOI: 10.1177/1352458514554052     Document Type: Article

References (18)

1. Curtin F, Hartung HP.. Novel therapeutic options for multiple sclerosis. Expert Rev Clin Pharmacol. 2014; 7: 91-104
2. Perron H, Geny C, Laurent A, et al. Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles. Res Virol. 1989; 140: 551-561
3. Perron H, Lalande B, Gratacap B, et al. Isolation of retrovirus from patients with multiple sclerosis. Lancet. 1991; 337: 862-863
4. Perron H, Garson JA, Bedin F, et al. Molecular identification of a novel retrovirus repeatedly isolated from patients with multiple sclerosis. The Collaborative Research Group on Multiple Sclerosis. Proc Natl Acad Sci U S A. 1997; 94: 7583-7588
5. Sotgiu S, Mameli G, Serra C, et al. Multiple sclerosis-associated retrovirus and progressive disability of multiple sclerosis. Mult Scler. 2010; 16: 1248-1251
6. Mameli G, Astone V, Arru G, et al. Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6. J Gen Virol. 2007; 88: 264-274
7. Perron H, Germi R, Bernard C, et al. Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler. 2012; 18: 1721-1736
8. Perron H, van Horssen J. HERV-WEnv protein is strongly upregulated in inflammatory multiple sclerosis lesions. Poster P355 presented at ECTRIMS, Copenhagen;;..
9. Rolland A, Jouvin-Marche E, Viret C, et al. The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses. J Immunol. 2006; 176: 7636-7644
10. Kremer D, Schichel T, Förster M, et al. Human endogenous retrovirus type W envelope protein inhibits oligodendroglial precursor cell differentiation. Ann Neurol. 2013; 74: 721-732
11. Curtin F, Lang AB, Perron H, et al. GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus: A first-in-humans randomized clinical study. Clin Ther. 2012; 34: 2268-2278
12. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011; 69: 292-302
13. Wang W, Wang EQ, Balthasar JP.. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008; 84: 548-558
14. Mould DR, Green B.. Pharmacokinetics and pharmacodynamics of monoclonal antibodies: Concepts and lessons for drug development. BioDrugs. 2010; 24: 23-39
15. Mameli G, Serra C, Astone V, et al. Inhibition of multiple-sclerosis-associated retrovirus as biomarker of interferon therapy. J Neurovirol. 2008; 14: 73-77
16. Arru G, Leoni S, Pugliatti M, et al. Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: A longitudinal cohort study. Mult Scler. 2014; 20: 174-182
17. Stpie A, Chalimoniuk M, Lubina-D'Browska N, et al. Effects of interferon β-1a and interferon β-1b monotherapies on selected serum cytokines and nitrite levels in patients with relapsing-remitting multiple sclerosis: A 3-year longitudinal study. Neuroimmunomodulation. 2013; 20: 213-222
18. Ramos-Cejudo J, Oreja-Guevara C, Stark Aroeira L, et al. Treatment with natalizumab in relapsing-remitting multiple sclerosis patients induces changes in inflammatory mechanism. J Clin Immunol. 2011; 31: 623-631