PMID- 23200102
OWN - NLM
STAT- MEDLINE
DCOM- 20130517
LR  - 20220408
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 12
DP  - 2012 Dec
TI  - GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple 
      sclerosis-associated endogenous retrovirus: a first-in-humans randomized clinical 
      study.
PG  - 2268-78
LID - S0149-2918(12)00649-2 [pii]
LID - 10.1016/j.clinthera.2012.11.006 [doi]
AB  - BACKGROUND: Human endogenous retrovirus (HERV) genes represent about 8% of the 
      human genome. A member of the HERV family W, the Multiple Sclerosis-Associated 
      Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a 
      proinflammatory and autoimmune cascade through its interaction with Toll-like 
      receptor 4. Due to its proinflammatory property and an inhibitory effect on 
      oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a 
      crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized 
      monoclonal antibody of the immunoglobulin G4 type, which is directed against 
      MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical 
      experimental models, a clinical development program was initiated. OBJECTIVE: 
      This study evaluated the safety profile, pharmacokinetic parameters, and 
      immunogenicity of GNbAC1 in healthy male volunteers. METHODS: In this 
      first-in-humans, Phase I, randomized, double-blind, placebo-controlled, 
      dose-escalation study, each subject received a single dose of IV GNbAC1 0.0025, 
      0.025, 0.15, 0.6, 2, or 6 mg/kg or inactive vehicle (placebo), infused over 1 
      hour. Tolerability and other laboratory parameters were observed, and regular 
      blood sampling was performed, to study the pharmacokinetic properties and 
      immunogenicity of this monoclonal antibody. RESULTS: A total of 33 male subjects 
      (mean age, 44 years) completed the study. GNbAC1 was well tolerated after dosing 
      in all subjects and in each dose cohort. Only minor and nonspecific adverse 
      events (AEs) were recorded; no serious AEs were reported. Pharmacokinetic data 
      show a dose-linear pharmacokinetic profile. The mean elimination half-life ranged 
      between 19 and 26 days, with therapeutically efficient concentrations maintained 
      over a 4-week periods at doses of 2 and 6 mg/kg. No emergence of anti-GNbAC1 
      antibodies were detected after dosing in any subject over the entire observation 
      period of 64 days. CONCLUSIONS: In these healthy male subjects, the safety and 
      pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are 
      expected to allow for the launch of a Phase II development program for this 
      innovative therapeutic approach in patients with multiple sclerosis. 
      ClinicalTrials.gov identifier: NCT01699555.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Curtin, Francois
AU  - Curtin F
AD  - GeNeuro SA, Geneva, Switzerland. fc@geneuro.com
FAU - Lang, Alois B
AU  - Lang AB
FAU - Perron, Herve
AU  - Perron H
FAU - Laumonier, Marion
AU  - Laumonier M
FAU - Vidal, Virginie
AU  - Vidal V
FAU - Porchet, Herve C
AU  - Porchet HC
FAU - Hartung, Hans-Peter
AU  - Hartung HP
LA  - eng
SI  - ClinicalTrials.gov/NCT01699555
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20121129
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Viral Envelope Proteins)
RN  - T32CR1A69R (temelimab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Endogenous Retroviruses/*immunology
MH  - Half-Life
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*immunology/virology
MH  - Viral Envelope Proteins/immunology
EDAT- 2012/12/04 06:00
MHDA- 2013/05/18 06:00
CRDT- 2012/12/04 06:00
PHST- 2012/10/18 00:00 [received]
PHST- 2012/11/12 00:00 [revised]
PHST- 2012/11/12 00:00 [accepted]
PHST- 2012/12/04 06:00 [entrez]
PHST- 2012/12/04 06:00 [pubmed]
PHST- 2013/05/18 06:00 [medline]
AID - S0149-2918(12)00649-2 [pii]
AID - 10.1016/j.clinthera.2012.11.006 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Dec;34(12):2268-78. doi: 10.1016/j.clinthera.2012.11.006. Epub 
      2012 Nov 29.