E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active ulcerative colitis in steroid refractory or steroid dependent patients |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the clinical response of Kappaproct given as a single dose of 30 mg compared to placebo. Responders are defined as patients showing a decrease in Disease Activity Index (DAI) score of at least 3 points, coupled with a reduction in levels of active NF-kB in intestinal mucosa analysed in biopsies from the patients. The differences in number of responders in the two groups (active dose and placebo) will be assessed. |
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E.2.2 | Secondary objectives of the trial |
* In an explorative manner study the immune response in blood and biopsies from the patients before and after treatment with Kappaproct and by analyzing blood from dosed patients monitor cytokine expression and other factors believed to play a role in inflammation. * To perform histopathological evaluation * To follow patients for 6 months after treatment. * To evaluate safety and tolerability of Kappaproct in one dose of 30 mg. * To confirm the diagnosis in biopsies using a diagnostic method based on real time polymerase chain reaction (PCR) analyses.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients, ≥18 years of age. 2. Well established UC, of mild or moderate degree, defined as a Schroeder DAI score of 6-11. 3. GCS treatment resistant or dependent (≥5mg per day of prednisolon or equivalent treatment for 4 weeks) or in cases of a known history of clinical steroid resistance not responding adequately to ≥5mg per day of prednisolon or equivalent treatment for ≥2 weeks. 4. Endoscopy score of ≥2. 5. At least one previous verified attack of UC within the last 3 years prior to randomization. 6. Current UC relapse with onset ≤12 months prior to randomization. 7. Current UC disease location should extend more than 10 cm from the anal verge but not beyond the left colonic flexure, as verified by an appropriate endoscopic method (rigid sigmoidoscopy/colonoscopy). 8. Visible blood in stools at least once within a week prior to randomization. 9. Infectious cause ruled out through negative stool culture. 10. If ongoing treatment with oral 5-ASA or SASP, the dose regimen must have been unchanged for at least 4 weeks prior to randomization and the therapy must have been initiatied at least 12 weeks prior to randomisation 11. Has given signed informed consent to participate in the study
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E.4 | Principal exclusion criteria |
1. Remicade less than 8 weeks ago. 2. Previous colectomy with ileorectal anastomosis. Patients that have undergone subtotal colectomy or ileosigmoidal anastomosis are eligible for inclusion. 3. Impaired rectal compliance. Eligible patients must be expected to be able to hold at least 50 mL. 4. An active infection, i.e. fever (>38oC). 5. Anaemia (Hb<100g/L). 6. History or presence of a clinical significant cardiovascular, hepatic, renal, haematological, endocrine, neurological or psychiatric disease or immune compromised state. 7. History or presence of colonic dysplasia, including adenomas within 5 years prior to randomization. 8. History or presence of any malignancy. 9. Any surgical event within 2 weeks prior to Baseline. 10. Treated with ciclosporine A, FK 506 or a similar biologic agent one month prior to Baseline. 11. Treated with Non-Steriodal Anti-Inflammatory Drugs (NSAID)s within one week prior to Baseline. 12. Treated with antibiotics within one week prior to Baseline. 13. Concomitant participation in another clinical study. Received an investigational drug within 3 months prior to randomization. 14. During the study pregnant or nursing women and women of childbearing potential (i.e. female who is not surgically sterile or postmenopausal) not using reliable contraceptive methods (barrier protection, hormonal contraception, intra-uterine device or abstinence). The same applies to men i.e not using reliable contraceptive methods such as condom and spermicide. 15. Inability to understand instructions/written information.
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E.5 End points |
E.5.1 | Primary end point(s) |
Response after one week treatment (30 mg Kappaproct or placebo), defined as a decrease in DAI score (a responder should have a decrease in DAI score of at least 3) coupled with a reduction in the level of active NF-kB in biopsies.
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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 | 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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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 | Information not present in EudraCT |
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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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |