Fontolizumab in moderate to severe Crohnʼs disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study Academic Article uri icon

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abstract

  • BACKGROUND: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. METHODS: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. RESULTS: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%-38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%-75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. CONCLUSIONS: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted.

authors

  • Reinisch, Walter
  • de Villiers, Williem
  • Bene, László
  • Simon, László
  • Rácz, István
  • Katz, Seymour
  • Altorjay, István
  • Feagan, Brian
  • Riff, Dennis
  • Bernstein, Charles N
  • Hommes, Daniel
  • Rutgeerts, Paul
  • Cortot, Antoine
  • Gaspari, Michael
  • Cheng, May
  • Pearce, Tillman
  • Sands, Bruce E

publication date

  • February 2010