E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Crohn’s disease is a serious disease in which there is swelling and ulceration of the gut wall. Symptoms may include pain, tiredness and the feeling of being generally unwell. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
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 |
Does 6-Mercaptopurine (also known as 6-MP) prevent or delay recurrence of Crohn's disease after surgery? |
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E.2.2 | Secondary objectives of the trial |
We shall also address these secondary research questions: 1. Can faecal calprotectin be used as a non-invasive marker of disease recurrence that may remove the need for colonoscopy in some patients? Calprotectin is a stable neutrophil derived faecal protein, that correlates with disease activity. Elevated calprotectin predicts relapse in patients in a medically induced remission but has not been assessed in the postoperative setting. 2. Do drug metabolite levels relate to clinical efficacy of 6MP? 3. Can we predict postoperative recurrence using clinical, genetic or serological data? The recent Montreal classification of Crohn’s disease has identified the need to integrate clinical, genetic and serological data. This study provides the opportunity to perform exploratory analyses of this data in a prospective, rigorously phenotyped cohort. 4. Does 6MP prevent or delay endoscopic evidence of recurrence? 5. Does endoscopic recurrence predict clinical recurrence? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. At least 16 years of age in Scotland and 18 years of age in England and Wales. 2. Established diagnosis of Crohn’s disease confirmed at recent resection. 3. Ileocolonic or small bowel resection within 3 months before screening. 4. No more than 100 cm of fixed small bowel resected in total. Previous ileocolonic resection is acceptable. 5. Able to start oral nutrition within the first 2 postoperative weeks. 6. Normal or heterozygous TPMT (activity present or reduced consistent with carrier status). 7. Able to provide written informed consent prior to screening and to comply with the requirements of the study protocol. 8. Off antibiotics 2 weeks prior to randomisation. |
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E.4 | Principal exclusion criteria |
1. Pregnancy at baseline or breast feeding. 2. A known hypersensitivity or intolerance to 6MP. 3. Pancreatitis associated with azathioprine. 4. Receiving an experimental treatment for Crohn’s disease in the 4 weeks prior to study entry. 5. Known to require further surgery at study entry i.e. for the removal of an abscess developing from the primary surgery. 6. Stricturoplasty procedure alone (Please note that stricturoplasty and resection procedure together will not be considered an exclusion.) 7. Presence of stoma. 8. Significant haematological, renal or hepatic dysfunction or clinically important lung disease (i.e. liver function tests >x2 upper limit of normal, Haemoglobin ≤10, total white blood cell count <3.5, Neutrophils <1.5, Platelets <100x106/l). 9. Systemic infection including hepatitis B, hepatitis C, HIV and active TB. 10. A diagnosis of indeterminate colitis or ulcerative colitis. 11. A history of illicit drug or alcohol abuse in the 1 year prior to study entry. 12. Active or untreated malignancy (excluding basal cell carcinoma and insitu tumours). (Patients who have had successful treatment for malignancy and have been in remission for more than 5 years may be considered for inclusion only after detailed discussion with, and written approval, from the patient's medical oncologist.) 13. Presence of a medical or psychiatric condition, disease or laboratory abnormality that in the opinion of the PI may place the subject at unacceptable risk during the study. 14. Homozygous deficient for TPMT (absent activity) 15. Evidence of untreated post-operative infection e.g. clostridium difficile, urinary tract infection or chest infection. If these have been appropriately treated in the opinion of the PI, and inclusion criteria 8 is met, this will not be considered an exclusion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical recurrence of Crohn’s disease (defined by a CDAI value of greater than 150 together with a 100 point rise in the CDAI score from baseline)), together with the need for anti-inflammatory rescue therapy or primary surgical intervention. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study Assessment Table (Page 29 of the Protocol) details all evaluation points for the trial. |
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E.5.2 | Secondary end point(s) |
1. The need for a second operation to remove recurrent Crohn’s disease from the anastomotic site. 2. Changes in self rated quality of life scores. 3. Endoscopic recurrence using the Rutgeerts scoring system. 4. Clinical recurrence of Crohn's disease (defined by a CDAI value of greater than 150 together with a 100 point rise in the CDAI score from baseline), OR the need for anti-inflammatory rescue therapy or primary surgical intervention. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study Assessment Table (Page 29 of the Protocol) details all evaluation points for the trial. |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | 30 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The end of study is defined as the last patient last visit. |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 30 |