Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.
BACKGROUND
Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis.


OBJECTIVE
To evaluate repifermin for the treatment of active ulcerative colitis.


METHODS
Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 microg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components.


RESULTS
At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 microg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups.


CONCLUSIONS
Intravenous repifermin at a dose of 1-50 microg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 microg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.
Sandborn
W J
WJ
Mayo Clinic, Rochester, MN, USA. sandborn.william@mayo.edu
Sands
B E
BE
Wolf
D C
DC
Valentine
J F
JF
Safdi
M
M
Katz
S
S
Isaacs
K L
KL
Wruble
L D
LD
Katz
J
J
Present
D H
DH
Loftus
E V
EV
Graeme-Cook
F
F
Odenheimer
D J
DJ
Hanauer
S B
SB
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000008:administration & dosage*; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D005765:Gastrointestinal Agents; D005346:Fibroblast Growth Factors