E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with inflammatory bowel diseae (Ulcerative colitis or Crohns disease) wh do not responding to first line therapy |
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E.1.1.1 | Medical condition in easily understood language |
Patients with inflammatory bowel disease (Ulcerative colitis and Crohns disease) who do not respond to treatment with steroids or 5-aminosalycalic acid (Ulcerative colitis) |
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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 |
To evaluate the efficacy and safety of low dose azathioprine and allopurinol versus standard azathioprine monotherapy in patients with inflammatory bowel disease. |
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E.2.2 | Secondary objectives of the trial |
To compare:
Time to remission
Steroid and biologic treatment free remission defined as Clinical remission (HBI ≤4 or SCCAI ≤2 ) at week 52 and no need for escalation of IBD therapy.
Clinical response after week 26 and week 52 (defined as Δ3 in HBI or Δ3 in SCCAI)
The proportion of patients with Fecal calprotectin <200 μg/g (<350 μg/g if Buhlman method is used) at week 26 and 52 .
Quality of life after 52 weeks using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS).
The proportion of patients who reach therapeutics levels of E-6TGN levels (230-450 pmol/L) at week 6 and week 26.
Adverse events defined as any untoward or unfavourable medical occurrence in a human subject
Effects on intestinal permeability and microbiota
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18-80 years at the time of inclusion, weight between 50 and 100 kg.
2. Willingness to comply with all trial procedures and being available for the duration of the trial.
3. Clinical and histological verified IBD eligible for treatment with thiopurines due to steroid dependence (failure to taper steroid or starting a second course of systemic steroids within one year) or due to the need for thiopurines for other reasons (disease phenotype, i.e post-surgery decision).
4. A written informed consent to participate in the study is signed before any study-related procedures are performed.
5. A normal TPMT activity measurement (>8.9 U/ml RBC) or normal TPMT genotype (*1/*1).
6. Naïve to thiopurine treatment
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E.4 | Principal exclusion criteria |
1. Biologic treatment (anti-TNF, vedoluzimab etc) within the last three months prior the study
2. Concurrent participation in another interventional therapy study.
3. Females who are pregnant or breastfeeding
4. Females of childbearing age and potential who are not willing or capable to use acceptable methods of contraception (oral contraceptives, condoms, diaphragms, intrauterine devices) during the entire study and for up to 3 months after the end-of-study evaluation.
5. Male patients who do not use acceptable barrier methods of contraception (condoms) during the entire course of the study and up to 3 months after the end-of-study evaluation.
6. Inability to follow the treatment protocol (as judged by the investigator)
7. Current treatment with Allopurinol.
8. Patients with gout that needs medical treatment.
9. Estimated GFR < 50 ml/ml
10. Persistent alanine aminotransferase U/L (ALT) above upper limit of the normal range.
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E.5 End points |
E.5.1 | Primary end point(s) |
Steroid and biologic treatment free remission defined as Clinical remission (HBI ≤4 or SCCAI ≤2 ) at week 26 and no need for escalation of IBD therapy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To compare:
Time to remission
Steroid and biologic treatment free remission defined as Clinical remission (HBI ≤4 or SCCAI ≤2 ) at week 52 and no need for escalation of IBD therapy.
Clinical response after week 26 and week 52 (defined as Δ3 in HBI or Δ3 in SCCAI)
The proportion of patients with Fecal calprotectin <200 μg/g (<350 μg/g if Buhlman method is used) at week 26 and 52 .
Quality of life after 52 weeks using Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and short health scale (SHS).
The proportion of patients who reach therapeutics levels of E-6TGN levels (230-450 pmol/L) at week 6 and week 26.
Adverse events defined as any untoward or unfavourable medical occurrence in a human subject
Effects on intestinal permeability and microbiota
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 weeks, 26 weeks, 52 weeks |
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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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
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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At week 52 or at withdrawal |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |