E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Active Crohn´s Disease |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 progesterone only; includes depot contraceptives - Intrauterine methods: intrauterine devices or systems 7. If using oral corticosteroids, mesalazine, or sulfasalazine, the start-date must be at least 4 weeks prior to study day 1. The dose of oral corticosteroids, mesalazine and/or sulfasalazine must be stable over the 2 weeks preceding study day 1. The daily dose of systemic corticosteroids should not be greater than 20 mg of prednisone equivalent or 9 mg budesonide. If using azathioprine, 6-mercaptopurine or methotrexate the dose must have been stable over the 8 weeks preceding study day 1. 8. If not using corticosteroids, azathioprine (AZA), 6-mercaptopurine (6-MP), mycophenolate mofetil or methotrexate (MTX) at the time of screening, the stop-date for any previous use of these agents must be at least 4 weeks prior to study day 1. 9. Patients who have received anti-TNF antibody therapy (infliximab, adalimumab, etanercept) must have received their last dosing at least 3 months prior to study day 1. 10. Patients who have received tacrolimus or cyclosporine must have received their last dosing at least 4 weeks prior to study day 1. 11. The screening laboratory tests must meet the following criteria: Hb > 8.5 g/dL (5.3 mmol/L) WBC > 3.5 x 109/L Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L SGOT (AST) and alkaline phosphatase levels must be within 2 times the upper limit of normal range 12. Patients must be able to adhere to the study visits and protocol requirements. 13. Patients must be able to give written informed consent and the consent must be obtained prior to any screening procedures.
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E.4 | Principal 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. Isolated small bowel involvement not assessable by endoscopy. 3. Ileo-/colostoma or extensive bowel resection (e.g., more than 100 cm of small bowel, proctocolectomy or colectomy with ileorectal anastomosis). Segmental colectomy is permitted. 4. Bowel surgery within the past three months, except for minor luminal surgery. 5. Immediate need for surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage. 6. Known fixed symptomatic stenosis of the small or large intestine. 7. Clinically significant abnormalities on chest X-ray or electrocardiogram. 8. Concomitant disease: a. Current signs or symptoms of severe, progressive or uncontrolled renal (creatinine > 250 mmol/L), hepatic (bilirubin > 25 mmol/L), hematological, endocrine, pulmonary, cardiac, neurological or cerebral disease (including a history of seizure disorders or ongoing chronic active conditions such as chronic active hepatitis) b. Previous diagnosis of, or known, malignancies c. 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 d. Active infection requiring antibiotic therapy e. Serum anti HCV positive, serum HBsAg positive, serum anti-HIV positive f. History of opportunistic infections such as herpes zoster within 2 months prior to screening, evidence of acute CMV or EBV, active Pneumocystic Carinii g. 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 h. Stool examination positive for enteric pathogens, pathogenic ova or parasites, or Clostridium Difficile toxin within 4 weeks prior to study day 1 9. Female patients who are pregnant or breast-feeding. 10. A psychiatric, addictive, or any disorder that comprises ability to give truly informed written consent for participation in this study. 11. Hypersensitivity to any component of the drug product. 12. Not available for follow-up assessment. 13. Has undergone or is undergoing treatment with another investigational drug or approved therapy for investigational use within 3 months prior to entry in this study 14. Has previously participated in this study
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E.5 End points |
E.5.1 | 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
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last follow up visit at week 24 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |