E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
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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 |
The primary objective of the study is to assess the clinical efficacy of TNF-K in adult subjects with moderate to severe active CD. Specifically, the study will assess the induction of clinical remission (CDAI≤150) |
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E.2.2 | Secondary objectives of the trial |
• To assess clinical response by CDAI (CDAI-70 and CDAI-100) • To assess mucosal improvement and healing by ileocolonoscopy • To assess changes in biological markers of disease activity • To assess microscopic and biological changes in ileocolonic mucosal tissue • To evaluate the safety of TNF-K treatment in subjects with moderate to severe active CD • To evaluate the anti-TNF-α and anti-Keyhole Limpet Hemocyanin (anti-KLH) antibody responses induced by TNF K • To evaluate the neutralizing anti-TNF-α antibody response induced by TNF-K
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female aged 18 to 65 years, inclusive. 2.Have had a diagnosis of Crohn’s disease for at least 6 months. 3.Moderate to severe active Crohn’s disease defined as a Crohn’s Disease Activity Index (CDAI) score ≥ 220 and ≤ 450, and presence of colonic mucosal ulcerations in at least 2 segments, or ulcerations on ≥ 10% of the mucosal surface if only one segment is involved. 4.Have developed secondary resistance to anti-TNF-α therapy. Secondary resistance must have followed at least 6 months of continuous anti-TNFα therapy during which a positive clinical response has been observed, according to the Investigator. Subjects can have received only one anti-TNF-α agent, and must have discontinued this treatment as follows: • Infliximab: a wash-out period of 8 weeks prior to the first administration of study drug; • Adalimumab: a wash-out period of 4 weeks prior to the first administration of study drug; • Certolizumab: a wash-out period of 8 weeks prior to the first administration of study drug; and/or Have developed intolerance to an anti-TNF-α treatment, provided that the observed adverse events are thought to be unrelated to the primary pharmacological effect of these agents (i.e. TNF-α blockade). 5.If receiving the medications listed below, must meet the outlined criteria: • Systemic corticosteroids: up to 25 mg/day of prednisone or equivalent, ongoing for at least 8 weeks, and with a stable dose for at least 2 weeks prior to the first administration of study drug; • Budesonide: up to 6 mg/day, ongoing for at least 8 weeks, and with a stable dose for at least 2 weeks prior to the first administration of study drug; • Methotrexate: up to 25 mg/week, ongoing for at least 8 weeks, and with a stable dose for at least 4 weeks prior to the first administration of study drug; • Azathioprine: up to 2.5 mg/kg/day, ongoing for at least 8 weeks, and with a stable dose for at least 4 weeks prior to the first administration of study drug; • Mercaptopurine: up to 1.5 mg/kg/day, ongoing for at least 8 weeks, and with a stable dose for at least 4 weeks prior to the first administration of study drug; • Antibiotics (metronidazole at 15-20 mg/kg per day and/or ciprofloxacin 500 mg bid) are allowed if ongoing for at least 4 weeks, and with a stable dose for at least 2 weeks prior to the first administration of study drug; • Sulfasalazine and mesalazine ongoing for at least 8 weeks, and with a stable dose of maximum 4g per day for at least 4 weeks prior to the first administration of study drug
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E.4 | Principal exclusion criteria |
1.Primary non-response to a previously received treatment directed against TNF α Or Intolerance related to the primary pharmacological effect of anti-TNF-α such as for instance, but not limited to, severe or opportunistic infections and demyelinating or autoimmune diseases. 2.History of severe systemic bacterial, fungal, viral, or parasitic infections within the 3 months prior to screening; or the occurrence of any acute infection within 2 weeks of the first administration of study drug. 3.Treatment with more than 2 doses over 30 mg of rectally administered corticosteroids in the 14 days preceding the first administration of study drug. 4.Treatment with immunosuppressive or immunomodulatory drugs, including, but not limited to: • B-cell depleting therapy (e.g., anti-CD20, anti-CD22) within 1 year of the first administration of study drug; • Cyclophosphamide within 12 weeks of the first administration of study drug; • Cyclosporine within 12 weeks of the first administration of study drug; • TNFα blockers other than infliximab, adalimumab or certolizumab within 12 weeks or 5 half lives of the first; administration of study drug, whichever is longer • Biological agents other than TNF-α blockers within 12 weeks or 5 half lives of the first administration of study drug, whichever is longer.
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy The same primary efficacy endpoint will be used for the interim and primary analyses, i.e., clinical remission, defined as a CDAI score ≤ 150 points at week 8. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 visit last patient, study report completion |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |