Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of NI-0401 (a fully human anti-CD3 monoclonal antibody) in patients with moderate to severe active Crohn's disease.

BACKGROUND NI-0401 is a fully human monoclonal antibody, which binds to the CD3 subunit of the T-cell receptor, causing modulation of T-cell activity. We investigated the safety and the ability to modulate the TCR-CD3 complex of NI-0401 in patients with active Crohn's disease (CD). METHODS A double-blind, placebo-controlled, randomized, multicenter, dose-escalating trial was conducted in CD patients age 18-70 years, a Crohn's Disease Activity Index (CDAI) of 220-450, and detectable levels of C-reactive protein. The primary outcome was safety and the ability of NI-0401 to modulate the TCR-CD3 complex on T cells. Efficacy parameters included the proportion of patients achieving remission (CDAI <150), clinical response (CDAI fall ≥100), and change from baseline in the CD Endoscopy Index of Severity (CDEIS). RESULTS Forty patients received placebo (n = 7) or NI-0401 (n = 33) 0.05-10 mg daily for 5 days. NI-0401 doses ≤1 mg were well tolerated. Infusion reactions occurred at doses ≥2 mg. The extent and duration of TCR-CD3 modulation increased with dose. No differences between groups were observed in the proportions of patients achieving clinical remission or response. The mean CDEIS at week 6 differed significantly between the 1-mg and placebo group. CONCLUSIONS NI-0401 was tolerated at doses ≤1 mg with manageable side effects. NI-0401 induced a dose-dependent modulation of the TCR-CD3 complex. No significant improvement of CDAI was observed but 1 mg NI-0401 demonstrated an improvement in CDEIS.