Intranasal administration of recombinant human cartilage glycoprotein-39 as a treatment for rheumatoid arthritis: a phase II, multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding trial.
BACKGROUND
Autoantigen-specific immunotherapy by mucosal tolerance induction via the intranasal route is an attractive therapeutic option for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Human cartilage glycoprotein-39 (HC gp-39) has been identified as a potential key autoantigen in RA. Based on animal studies, intranasal administration of the autoantigen is hypothesised to induce immunological tolerance in patients with RA and to ameliorate disease activity. In a phase I/IIA clinical trial in patients with RA, intranasal application of HC gp-39 was safe and well tolerated.


OBJECTIVE
To investigate the efficacy of intranasally administered fully human, recombinant HC gp-39 (Org 39141) by a large clinical study.


METHODS
In a 13-week multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding, proof-of-concept trial, patients with RA (disease-modifying antirheumatic drug (DMARD) naive or after washout of DMARD treatment) were randomised to receive either intranasal applications of placebo or HC gp-39 in doses of 30, 150, 300 or 600 microg, once a week. The primary efficacy variable was the 28 joint count Disease Activity Score (DAS28).


RESULTS
During the treatment period the DAS28 decreased similarly for all treatment groups-including placebo-indicating lack of efficacy of intranasal HC gp-39 treatment in the current setting. Safety variables were similar for all study groups.


CONCLUSIONS
It was concluded that with the treatment protocol used (dose levels and frequency of dosing), intranasal treatment with Org 39141 was safe but did not result in more clinical improvement than in placebo-treated patients.
Landewé
Robert B M
RB
NV Organon (Schering-Plough), Molenstraat 110, Oss, The Netherlands.
Houbiers
Jos G A
JG
Van den Bosch
Filip
F
in't Hout
Joanna
J
Verschueren
Patrick C P M
PC
Meijerink
Jan H
JH
van den Hoogen
Frank H J
FH
Masek
Bedrich A
BA
Bruyn
George A W
GA
Wouters
Jacques M G W
JM
Voskuyl
Alexandre E
AE
van Laar
Jacob M
JM
Bijlsma
Johannes J W
JJ
van der Heijde
Désirée M F M
DM
Breedveld
Ferdinand C
FC
van de Putte
Leo B A
LB
Miltenburg
André M M
AM
de Keyser
Filip
F
D054392:Adipokines; D000281:Administration, Intranasal; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000071451:Chitinase-3-Like Protein 1; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D037102:Lectins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome
D054392:Adipokines; D018501:Antirheumatic Agents; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D037102:Lectins; D011994:Recombinant Proteins