| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Ulcerative colitis |
| colitis ulcerosa |
|
| E.1.1.1 | Medical condition in easily understood language |
| ulcerative colitis |
| colitis ulcerosa |
|
| 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 | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045365 |
| E.1.2 | Term | Ulcerative colitis |
| E.1.2 | System Organ Class | 100000004856 |
|
| 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 objective of this study is to investigate whether intensive, personalized IFX dosing by using a pharmacokinetics driven dashboard system during the induction phase in patients with acute severe UC leads to increased treatment success (as defined by sustained clinical response and endoscopic response at week 6) as compared to the standard dosing. |
|
| E.2.2 | Secondary objectives of the trial |
-Proportion of patients in remission at week 6 and 26 as measured by the Mayo score
-Proportion of patients with response at week 6 and 26 as measured by the Mayo score
-Proportion of patients in clinical remission at week 6 and 26 as measured by the Simple Clinical Colitis Activity Index
-Proportion of patients in corticosteroid-free remission at week 26 as measured by the Simple Clinical Colitis Activity Index
-Proportion of patients with clinical remission measured by the Lichtiger scale at week 6 and 26
-Proportion of patients in biochemical remission at week 6 and 26
-Proportion of patients with endoscopic response as measured by the Mayo endoscopic subscore
-Proportion of patients with endoscopic remission at week 6 and 26 as measured by the UCEIS
-Proportion of patients with mucosal healing at week 6 and 26 as measured by the Mayo endoscopic subscore
-Proportion of patients with complete mucosal healing at week 6 and 26
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult UC patients (≥18 years)
2. Admission with acute severe UC (defined patients with bloody diarrhoea ≥ 6/day and any signs of systemic toxicity (pulse > 90/min, temperature > 37.8°C, haemoglobin < 105 g/l, erythrocyte sedimentation rate [ESR] > 30 mm/h, or C-reactive protein [CRP] > 30 mg/l)
3. Failure to intravenous steroid treatment as defined by the Oxford criteria (more than 8 stools/d or 3-8 stools/d and CRP≥45 on day 3 after starting iv steroid treatment)
4. Patients going through baseline endoscopy and biopsy sampling (including CMV) before starting on IFX treatment
5. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
6. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
7. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
|
|
| E.4 | Principal exclusion criteria |
1. Patients at imminent need of surgery as judged by the treating clinician
2. Previous use of IFX
3. Enteric pathogens (such as Salmonella, Shigella, Yershinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening
4. Active participation in another interventional trial
5. Patients with Crohn’s disease or IBD-U
6. Patients with abdominal abscess
7. Patients with colonic stricture
8. Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma, which has been removed
9. Active or latent tuberculosis (screening according to national guidelines)
10. Cardiac failure in NYHA stage III-IV
11. History of demyelinating disease
12. Recent live vaccination
13. Patients with ongoing acute/chronic infection (including but not limited to HIV, hepatitis B and C) with the exception of chronic herpes labialis or cervical HPV
14. History of cancer in the last 5 years with the exception of non-melanoma skin cancer
15. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures
16. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures
17. Patients unable to attend all study visits
18. Patients with a history of non-compliance with clinical study protocols
19. Contraindication for endoscopy
20. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer
21. Patients who received cyclosporine in the previous 14 days
22. Pregnancy and lactation
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Treatment success at week 6, defined as a combination of
• clinical response (defined as a Lichtiger score of < 10 points with a decrease of at least 3 points compared to baseline) AND
• endoscopic response (defined as a decrease of at least 2 points in the UCEIS at week 6 endoscopy compared to baseline)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Proportion of patients in remission at week 6 and 26 as measured by the Mayo score (Mayo score ≤ 2 with no individual subscore >1)
- Proportion of patients with response at week 6 and 26 as measured by the Mayo score (decrease in Mayo score ≥ 3 points and ≥30% from baseline and a decrease in the rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore of 0 or 1)
- Proportion of patients in clinical remission at week 6 and 26 as measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
- Proportion of patients in corticosteroid-free remission at week 26 as measured by the Simple Clinical Colitis Activity Index (SCCAI score ≤ 2)
- Proportion of patients with clinical remission measured by the Lichtiger scale at week 6 and 26 (Lichtiger score ≤ 3)
-Days in clinical response (defined as Lichtiger score of <10 points with a decrease of at least 3 points compared to baseline) and remission ( defined as Lichtiger score < 3) throughout week 0-6
- Proportion of patients in biochemical remission at week 6 and 26 (CRP ≤ 5.0 mg/L and fecal calprotectin < 250 mg/g)
- Proportion of patients with endoscopic response as measured by the Mayo endoscopic subscore (≥1 point improvement) at week 6 and 26
- Proportion of patients with endoscopic remission measured by the UCEIS (UCEIS 1 point on all descriptors)
- Proportion of patients with mucosal healing at week 6 and 26 as measured by the Mayo endoscopic subscore (eMayo 0 or 1)
- Proportion of patients with complete mucosal healing at week 6 and 26 as measured by the Mayo endoscopic subscore (eMayo 0)
- Degree of histological improvement at week 6 and 26 compared to baseline as defined by the Robarts histopathology index
- Proportion of patients reaching minimally clinically important difference in quality of life at week 6 and week 26 compared to baseline as assessed by the IBDQ and EQ-5D-5L questionnaire
- Colectomy rates at week 26
- Total IFX dosing (mg/kg) until week 26
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| same medicinal substance but as standard dosing |
|
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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