E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn’s disease |
De ziekte van Crohn |
La maladie de Crohn |
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E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory bowel disease |
Chronische inflammatoire darmziekte |
la maladie inflammatoire chronique de l'intestin |
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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 assess the clinical effect of ustekinumab re-induction ≈6mg/kg IV followed by either 90 mg SC Q8W or 90 mg SC Q4W in patients with CD who show a secondary loss of response over time |
Het effect onderzoeken van een herintroductie van ustekinumab ~6mg/kg intraveneus, gevolgd door twee verschillende onderhoudsbehandelingen 90mg subcutaan elke 8 of elke 4 weken op klinische, biologische en farmacologische resultaten in patiënten met de ziekte van Crohn die initiëel beterschap ervaarden, maar deze over tijd terug verloren |
Examiner l’effet d’une réintroduction d’ustékinumab ~6 mg/kg par voie intraveineuse, suivie de deux traitements d’entretien différents 90 mg par voie sous-cutanée toutes les 8 semaines comparé à toutes les 4 semaines en terme de résultats cliniques, biologiques et pharmacologiques chez des patients atteints de la maladie de Crohn ayant connu une amélioration initiale, mais l’ayant perdue au fil du temps. |
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E.2.2 | Secondary objectives of the trial |
to assess the endoscopic and biochemical effects of, pharmacodynamic and pharmacokinetic aspects of, quality of life of patients treated with, asses safety and socio-economic impact of ustekinumab re-induction ≈6mg/kg IV followed by either 90 mg SC Q8W or Q4W in patients with CD who show a secondary loss of response over time |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 years 2. Diagnosis of Crohn’s disease for at least 3 months prior to visit 1 by endoscopic and/or radiologic examination. 3. Patient currently treated with UST, independent of previous biological exposure. 4. Patients treated with maintenance UST SC 90 mg Q8W (meaning after a minimum of 2 SC injections) 5. Documented primary response at any time point during induction (up to week 20) defined as a clinical response (physician discretion) AND confirmed by either any of the following: 1. A documented decrease in biomarkers based on a value during induction period compared to a value prior to UST induction (max. 3 months prior to start of UST induction) a. A decrease in CRP OR b. A decrease in FCP 2. A documented endoscopic improvement (evaluation during the induction period compared to an evaluation prior to UST induction (max. 6 months prior to start of UST induction) 6. Documented loss of response after induction (> week 16) assessed by the physician as moderate to severe active Crohn’s disease. The increase in symptoms reported by the patient is defined as: PRO-2 (AP > 1 AND SF > 3) AND confirmed by either any of the following: 1. Documentation of endoscopic lesions in at least one segment of the ileum or colon as assessed by ileocolonoscopy AND a documented increase in biomarkers based on an increased value compared to the lowest value obtained during induction or after week 16 UST induction. a. An increase in CRP and >5 mg/L OR b. An increase in FCP and > 250µg/mg 2. A documented relapse on endoscopy: Presence of mucosal ulcers in at least one segment of the ileum or colon and a SES-CD ≥ 6 (for patients with isolated ileitis ≥4), as assessed by ileocolonoscopy 7. Adequate contraception in female of reproductive age (oral contraception, intra uterine device, sterilisation or barrier method) 8. Have the capacity to understand and sign an informed consent form. 9. Be able to adhere to the study visit schedule and other protocol requirements. 10. All Crohn's Disease treatments stable for at least 2 weeks prior to baseline
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E.4 | Principal exclusion criteria |
1. Ongoing treatment with a. other concomitant biological (vedolizumab, anti-TNF) b. Steroids >20 mg prednisolone or equivalent at baseline (budesonide >6 mg; >5 mg beclomethasone dipropionate at baseline) c. Q4w ustekinumab 2. Women that are pregnant, nursing, or planning pregnancy 3. Have current signs or symptoms of infection confirmed by positive stool or blood testing (including gastrointestinal pathogens, TB, HIV, Hep B, Hep C). 4. Patients with a positive stool sample for gastrointestinal pathogen including Clostridium difficile. 5. Patients with an impassable stenosis even after attempt of endoscopic balloon dilation. 6. Patients with an abscess |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with steroid free clinical remission (PRO-2 remission: AP ≤ 1 AND SF ≤ 3) and FCP <250µg/g. |
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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) |
Proportion of patients with complete endoscopic remission (SES-CD <3) Proportion of patients with endoscopic remission (SES-CD <5) Proportion of patients with endoscopic response (≥50% decrease in SES-CD) Proportion of patients with clinical remission (PRO-2 remission: AP ≤ 1 AND SF ≤ 3) Proportion of patients with biomarker remission Proportion of patients with SAE in the different treatment arms
Proportion of patients with clinical remission (PRO-2 remission: AP ≤ 1 AND SF ≤ 3)
Proportion of patients with UST TC > 1.4 μg/mL
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 48
at week 8 after IV re-induction
at all timepoints of the study corresponding to each studyvisit ( week 4, 8, 12, 20, 28, 36, 44 and 48) |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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.8.2.4 | 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 | 16 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |