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

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. Inflamm Bowel Dis 2009