Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: A randomized, double-blind, placebo-controlled, dose-escalation trial

W. J. Sandborn, B. E. Sands, D. C. Wolf, J. F. Valentine, M. Safdi, S. Katz, K. L. Isaacs, L. D. Wruble, J. Katz, D. H. Present, Edward Vincent Loftus, Jr, F. Graeme-Cook, D. J. Odenheimer, S. B. Hanauer

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Abstract

Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. Aim: 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 μg/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 μg/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 μg/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 μg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

Original languageEnglish (US)
Pages (from-to)1355-1364
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume17
Issue number11
DOIs
StatePublished - Jun 1 2003

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Fibroblast Growth Factor 10
Ulcerative Colitis
Placebos
Therapeutics
Maximum Tolerated Dose
Colitis

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology (medical)

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Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis : A randomized, double-blind, placebo-controlled, dose-escalation trial. / Sandborn, W. J.; Sands, B. E.; Wolf, D. C.; Valentine, J. F.; Safdi, M.; Katz, S.; Isaacs, K. L.; Wruble, L. D.; Katz, J.; Present, D. H.; Loftus, Jr, Edward Vincent; Graeme-Cook, F.; Odenheimer, D. J.; Hanauer, S. B.

In: Alimentary Pharmacology and Therapeutics, Vol. 17, No. 11, 01.06.2003, p. 1355-1364.

Research output: Contribution to journalArticle

Sandborn, WJ, Sands, BE, Wolf, DC, Valentine, JF, Safdi, M, Katz, S, Isaacs, KL, Wruble, LD, Katz, J, Present, DH, Loftus, Jr, EV, Graeme-Cook, F, Odenheimer, DJ & Hanauer, SB 2003, 'Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: A randomized, double-blind, placebo-controlled, dose-escalation trial', Alimentary Pharmacology and Therapeutics, vol. 17, no. 11, pp. 1355-1364. https://doi.org/10.1046/j.1365-2036.2003.01589.x
Sandborn, W. J. ; Sands, B. E. ; Wolf, D. C. ; Valentine, J. F. ; Safdi, M. ; Katz, S. ; Isaacs, K. L. ; Wruble, L. D. ; Katz, J. ; Present, D. H. ; Loftus, Jr, Edward Vincent ; Graeme-Cook, F. ; Odenheimer, D. J. ; Hanauer, S. B. / Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis : A randomized, double-blind, placebo-controlled, dose-escalation trial. In: Alimentary Pharmacology and Therapeutics. 2003 ; Vol. 17, No. 11. pp. 1355-1364.
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abstract = "Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. Aim: 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 μg/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 μg/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 μg/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 μg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.",
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T2 - A randomized, double-blind, placebo-controlled, dose-escalation trial

AU - Sandborn, W. J.

AU - Sands, B. E.

AU - Wolf, D. C.

AU - Valentine, J. F.

AU - Safdi, M.

AU - Katz, S.

AU - Isaacs, K. L.

AU - Wruble, L. D.

AU - Katz, J.

AU - Present, D. H.

AU - Loftus, Jr, Edward Vincent

AU - Graeme-Cook, F.

AU - Odenheimer, D. J.

AU - Hanauer, S. B.

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N2 - Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. Aim: 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 μg/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 μg/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 μg/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 μg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

AB - Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. Aim: 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 μg/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 μg/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 μg/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 μg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study.

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