A phase 1, double-blind, placebo-controlled study evaluating single subcutaneous administrations of a human interleukin-12/23 monoclonal antibody in subjects with plaque psoriasis.
OBJECTIVE
To evaluate safety, pharmacokinetics, pharmacodynamics, and clinical response of single subcutaneous (s.c.) administrations of a human monoclonal antibody against the p40 subunit of IL-12/23 (IL-12/23 mAb) in subjects with moderate-to-severe psoriasis.


METHODS
Twenty-one subjects were enrolled sequentially into 4 dose cohorts (0.27, 0.675, 1.35, and 2.7 mg/kg) and randomized to IL-12/23 mAb or placebo in a 4:1 ratio. Laboratory/clinical parameters and pharmacokinetics were evaluated through Week 24; mRNA cytokine expression was measured in psoriatic plaques at Week 1.


RESULTS
Mostly mild adverse events and no serious adverse events were reported. The pharmacokinetics (Cmax and AUC) of IL-12/23 mAb increased in an approximately dose-proportional manner. Of the 17 subjects who received IL-12/23 mAb, 13 achieved PASI 75 (compared with no placebo subjects). mRNA expression of IL-8, IL-18, and IFN-gamma in psoriatic plaques decreased in subjects with sustained Psoriasis Area and Severity Index (PASI) improvement.


CONCLUSIONS
Interpretation of results is limited due to the small sample size in each dose cohort.


CONCLUSIONS
A single s.c. administration of IL-12/23 mAb was well tolerated and showed clinical response in subjects with moderate-to-severe psoriasis.
Gottlieb
Alice B
AB
Department of Dermatology, Tufts-New England Medical Center, Boston, MA 02111, USA. agottlieb@tufts-nemc.org
Cooper
Kevin D
KD
McCormick
Thomas S
TS
Toichi
Eiko
E
Everitt
Daniel E
DE
Frederick
Bart
B
Zhu
Yaowei
Y
Pendley
Charles E
CE
Graham
Martin A
MA
Mascelli
Mary Ann
MA
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D007279:Injections, Subcutaneous; D053762:Interleukin-12 Subunit p40 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011565:Psoriasis / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D053762:Interleukin-12 Subunit p40; D010919:Placebos