NI-0401 in Active Crohn's Disease

A Phase I/IIa, Double-Blind, Placebo-Controlled, Dose-Escalation Study of NI-0401 in Patients With Moderate to Severe Active Crohn´s Disease

The purpose of the study is to assess the safety and tolerability of daily intravenous NI-0401 treatment, compared to matching placebo. And to assess the ability of NI-0401 to modulate the CD3 complex on T-cells.

Study Overview

• Status: Completed
• Conditions: Moderate to Severe Crohn's Disease
• Intervention / Treatment: Drug: Placebo; Biological: NI-0401 (anti-CD3 mAB)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Men and women between 18 and 70 years of age.
2. Crohn's Disease Activity Index (CDAI) between 220 and 450.
3. Raised plasma CRP level.
4. Endoscopic inflammation.
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.

Main Exclusion criteria

1. Have received or are planned to receive immunization with a live vaccine within 6 weeks prior to receiving study drug and 12 weeks after treatment cessation.

2. Concomitant disease:

   • Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurological or cerebral disease (including a history of seizure disorders or ongoing chronic active conditions such as chronic active hepatitis)
   • Previous diagnosis of, or known, malignancies
   • Severe infections, such as hepatitis, pneumonia or pyelonephritis, in the past three months. Less serious infections in the past 3 months, such as acute upper respiratory tract infection (colds) or uncompliant urinary tract infection are permitted at the discretion of the investigator
   • Active infection requiring antibiotic therapy
   • Serum anti HCV positive, serum HBsAg positive, serum anti-HIV positive
   • History of opportunistic infections such as herpes zoster within 2 months prior to screening, evidence of acute CMV or EBV, active Pneumocystic Carinii
   • History of active tuberculosis (TB) or currently undergoing treatment for TB. Patients with a positive TB skin test or chest x-ray are ineligible. Patients with a history of bacille Calmette Guerin (BCG) vaccination and a newly positive TB skin test or a chest X-ray showing fibrotic lesions consistent with previous TB are ineligible. The PPD skin test must be read between 48 and 72 hours
   • Stool examination positive for enteric pathogens, pathogenic ova or parasites, or Clostridium Difficile toxin within 4 weeks prior to Study Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Biological: NI-0401 (anti-CD3 mAB); 0.05 mg up to 10 mg
Placebo Comparator: 1	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of intravenous NI-0401 .	24 weeks

Secondary Outcome Measures

Outcome Measure
Immunological response defined as the percent change in the modulation of the CD3 complex on T-cells

Collaborators and Investigators

• Sponsor: Light Chain Bioscience - Novimmune SA
• Investigators: Principal Investigator: Janeeke Van der Woude, MD, Erasmus Medisch Centrum

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: March 6, 2008
• First Posted (Estimate): March 7, 2008

Study Record Updates

• Last Update Posted (Estimate): March 7, 2008
• Last Update Submitted That Met QC Criteria: March 6, 2008
• Last Verified: February 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Muromonab-CD3
• Other Study ID Numbers: NI-0401-01