E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Induction of remission in active Crohn´s disease |
|
E.1.1.1 | Medical condition in easily understood language |
Acute phase of the inflammatory bowel disease "Crohn's Disease" |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
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 evaluate the efficacy of three doses of oral TSO suspension vs. placebo for the induction of remission in Crohn’s disease. |
|
E.2.2 | Secondary objectives of the trial |
To study safety and tolerability (adverse events, laboratory parameters) and immunological effects of TSO suspension,
To evaluate the mucosal healing rate after 12-week treatment with TSO suspension,
To assess patients’ quality of life.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent,
2. Man or woman between 18 and 75 years of age,
3. Established diagnosis of Crohn’s disease (CD) confirmed by endoscopic and histological, or endoscopic and radiological criteria, all of which since
at least 3 months prior to screening,
4. Localisation of CD either in terminal ileum (L1), in colon (L2) or
ileocolitis (L3), all without upper gastrointestinal involvement (- L4)
according to the Montreal classification (2005),
5. CDAI ≥220 and ≤ 350 at baseline,
6. Serum CRP level ≥ 2 x upper limit of normal (ULN) or stool calprotectin
> ULN at screening,
7. Haemoglobin ≥ 10 g/dl at screening,
8. White blood cell count ≤ 13.0 Gpt/L at screening,
9. Platelet count ≥ lower limit of normal at screening,
10. Negative pregnancy test in females of childbearing potential,
11. Women of child-bearing potential have to apply during the entire duration
of the study a highly effective method of birth control, which is defined as
those which result in a low failure rate (i.e., less than 1% per year) when
used constantly and correctly such as implants, injectables, combined oral
contraceptive method, or some IUDs. The investigator is responsible for
determining whether the subject has this adequate birth control for study
participation. |
|
E.4 | Principal exclusion criteria |
1. Known Crohn’s lesions in the upper GI-tract (up to and including the
jejunum) with present symptoms,
2. Bowel surgery within the last 3 months prior to baseline,
3. Resection of more than 50 cm of the ileum,
4. Ileostomy or colostomy,
5. Septic complications,
6. Evidence of infectious diarrhoea (i.e., pathogenic bacteria or Clostridium
difficile toxin in stool culture),
7. Abscess, perforation, active fistulas, or active perianal lesions,
8. Immediate surgery required (e.g., major stenosis, serious bleeding,
peritonitis, ileus),
9. Clinical signs of stricturing disease,
10. Parenteral or tube feeding,
11. Abnormal hepatic function (ALT or ALP > 2.5 x ULN at screening), liver
cirrhosis, or portal hypertension,
12. Abnormal renal function (Cystatin C > ULN) at screening,
13. Acute EBV infection at screening,
14. Any severe concomitant cardiovascular, renal, endocrine, or psychiatric
disorder, which in the opinion of the investigator might have an influence
on the patient’s compliance or the interpretation of the results,
15. Any condition associated with significant immunosuppression,
16. Active malignancy or treatment with anticancer drugs during the last
5 years. Patients with a history of cancer and at least five years of
uneventful follow up and no signs of recurrence may be eligible as well as
patients with treated, non-metastatic cancers (e.g., basalioma),
17. Treatment with immunosuppressants or anti-cancer drugs, e.g., anti-TNF-
α agents, anti-integrin agents, azathioprine or 6-MP, 6-thioguanine,
methotrexate, tacrolimus, cyclophosphamide, or cyclosporine within the
last 3 months prior to baseline,
18. Treatment with antibiotics (e.g., metronidazole or ciprofloxacin),
antiparasitic medications within the last 2 weeks prior to baseline,
19. Treatment with topical or systemic glucocorticosteroid within the last 4 weeks prior to baseline, or within the last 8 weeks, if patients have been
treated for longer than 3 months,
20. Patients known to be steroid-dependent or refractory, as defined in ECCO
consensus guideline 2010,
21. Patients being unresponsive to both treatment with a biologic (e.g., anti-
TNF-α agents or anti-integrin agents) AND treatment with a thiopurine
(i.e., azathioprine, 6-MP, or 6-thioguanine),
22. Application of non-steroidal anti-inflammatory drugs (NSAIDs) within
2 weeks before baseline visit for more than 3 consecutive days, except
acetylsalicylic acid ≤ 350 mg/d which is allowed,
23. Immunisation with live vaccines within 12 weeks prior to baseline or
during the study,
24. Travelling within the last 12 weeks prior to baseline or during study
participation to countries outside of Europe, U.S.A., or Canada,
25. Well-founded doubt about the patient’s cooperation, e.g., because of
addiction to alcohol or drugs,
26. Existing or intended pregnancy or breast-feeding,
27. Participation in another clinical trial within the last 30 days, simultaneous
participation in another clinical trial, or previous participation in the
TSU-2/CDA trial and having received study drug. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Rate of patients with clinical remission at week 12 (LOCF) defined as a CDAI< 150 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Rate of patients with a reduction of > 100 points in CDAI
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
at weeks 2, 4, 6, 8, 10, and 12
|
|
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 55 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 | No |
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 |
Austria |
Czech Republic |
Denmark |
Germany |
Switzerland |
|
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
|
The study end is defined as “last patient out” (LPO), i.e., “last patient having his/her last visit”. |
|
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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |