Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose study

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

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 285 KB
• Volume: 16
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.21038

✦ Synopsis

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.