期刊
INFLAMMATORY BOWEL DISEASES
卷 16, 期 10, 页码 1708-1716出版社
OXFORD UNIV PRESS INC
DOI: 10.1002/ibd.21252
关键词
Crohn's disease; biologic therapies; anti-CD3; phase I clinical trial; NI-0401
资金
- NovImmune
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 220450, 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.
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