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 |
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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 | 20.0 |
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 |
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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 investigate the exposure-response relationship of ustekinumab upon IV and SC administration through intensive sampling and identify the best time point to measure ustekinumab during induction to predict long-term outcome and the best time point during maintenance to maintain this outcome |
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E.2.2 | Secondary objectives of the trial |
To investigate which covariates influence the ustekinumab concentration upon IV and SC administration Additional objectives: 1. Identify biomarkers that can predict treatment outcome 2. Investigate if ustekinumab can be found in the faeces after the first IV infusion and if its presence correlates with treatment outcome 3. Compare blood sampling via DBS with volumetric absorptive micro sampling |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• At least 18 years old at inclusion • Established diagnosis of Crohn’s disease with clinical disease activity (Harvery-Bradshaw index (HBI) > 4) and endoscopic activity (Simple Endoscopic Score for Crohn’s disease (SES-CD)≥ 6 or SES-CD ≥ 4 in patients with ileitis only) • Adequate contraception in female of reproductive age (oral contraception, intra uterine device, sterilisation or barrier method) • Participants must sign an informed consent form indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
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E.4 | Principal exclusion criteria |
• Patients who previously received ustekinumab or an anti-IL23 antibody • Patients with ostomies • Women that are pregnant, nursing, or planning pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in ustekinumab concentrations between patients with an endoscopic response (defined as minimal 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD) from baseline) and patients without endoscopic response |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 24 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Difference in ustekinumab concentration between patients achieving a certain outcome (see list below) and patients not achieving that outcome (the list is unranked) List of outcomes: • Clinical response defined as reduction in Harvery-Bradshaw index (HBI) of ≥3 from baseline • Clinical remission defined as reduction in HBI ≤4 • Biological response defined as a minimal 50% decrease in C-reactive protein (CRP) from baseline or CRP < 5, in patients with CRP ≥ 5 at baseline • Biological remission defined as a CRP < 5, in patients with CRP ≥ 5 at baseline • Minimal 50% decrease in faecal calprotectin from baseline by week 8 • Faecal calprotectin < 250 µg/g by week 24 • Endoscopic remission defined as SES-CD ≤ 3 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 24 weeks of treatment unless specified otherwise in the endpoints |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluate if there is an association between the drug concentration in the blood (instead of the administered dose) and therapeutic response, at different time points during treatment --> can measured drug concentrations be used to predict outcome? |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |