A Phase I/IIa, Double-blind, Randomized, Placebo-controlled, Dose-Escalation Study of NI-0401 in Patients with Moderate to Severe Active Crohn´s Disease

INTERVENTION: Product Name: NI‐0401 Product Code: NI‐0401 Pharmaceutical Form: Solution for infusion Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Moderate to Severe Active Crohn´s Disease PRIMARY OUTCOME: Main Objective: To assess the safety and tolerability of daily intravenous NI‐0401 treatment for five consecutive days, in patients with moderate to severe active Crohn’s disease, compared to matching placebo; ; To assess the ability of NI‐0401 to modulate the CD3 complex on T‐cells, measured as the percent change in CD3 complex modulation at Study Day 8.; Primary end point(s): 1. Safety and tolerability of a 5‐day treatment course of intravenous NI‐0401 in patients with moderate to severe active CD. Adverse Events (AEs) and Serious Adverse Events (SAEs) will be documented throughout the study period (24 weeks) and will be characterized according to their incidence, severity and relationship to the study drug.; ; Specific assessments will be made to evaluate the incidence and severity of a Cytokine Release Syndrome (CRS) and effects on immunological parameters including T‐cell number and function.; ; 2. Immunological response defined as the percent change in the modulation of the CD3 complex on T‐cells; Secondary Objective: To assess therapeutic responses to NI‐0401 over time, compared to matching placebo, including the induction of clinical response and clinical remission over time, the maintenance of response and remission, and the time to clinical response and remission, compared to matching placebo and as assessed by changes in the CDAI ; ; To assess the effect of NI‐0401 on mucosal health as assessed by the Rutgeerts and CDEIS scores, compared to matching placebo; ; To assess the pharmacokinetics and pharmacodynamics of NI‐0401 administered intravenously for 5 consecutive days in patients with moderate to severe active Crohn’s disease; ; To assess the effect of NI‐0401 on T‐cell function, as assessed by the evaluation of markers of T‐cell function, including FACS analysis of cell surface antigens; ; To assess the effect of NI‐0401 on the plasma viral load of the EBV, CMV, and JC viruses during the study period, compared to matching placebo; INCLUSION CRITERIA: 1. Men and women ³ 18 and < 70 years of age. 2. Crohn’s Disease Activity Index (CDAI) of >220 to <450 and having exhausted all other possible treatment options. 3. Detectable plasma CRP level. 4. Endoscopic inflammation defined as the presence of any inflammatory mucosal lesion. 5. Crohn’s disease of at least 6 months duration, with colitis, ileitis, or ileocolitis, confirmed by endoscopy and histology within 28 days of study day 1. 6. Men and women of childbearing potential must use adequate birth control measures until 6 month after receiving study drug. Women of childbearing potential and their partners are required to use two forms of contraception. Men with partners of child bearing potential are required to use barrier contraception, in addition to their partners using another method. Acceptable forms of contraception are as follows: ‐ Barrier methods: condoms, diaphragms, cervical caps ‐ Hormonal contraceptives: combination or pro