E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn's disease |
Ziekte van Crohn |
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E.1.1.1 | Medical condition in easily understood language |
Crohn's disease |
Ziekte van Crohn |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Key objective of this study is to demonstrate non-inferiority of disease activity guided adalimumab injection interval lengthening compared to usual care (continued dosing) in maintaining remission in CD at 48 weeks of follow-up. |
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E.2.2 | Secondary objectives of the trial |
- The proportion of patients in remission with interval extension at 48 weeks. - The proportion of persistent flares (persistent flare is defined as >8 weeks HBI increase ≥ 5, FC >250 µg/g and/or CRP >5 mg/L) between the interval extension and usual care groups. - To compare quality of life maintenance between interval extension and usual care groups. - To compare disease activity (HBI) every 3 months during the follow-up of 48 weeks between interval extension and usual care. - To identify factors, which are linked to successful interval extension (e.g. baseline patient and treatment characteristics, FC, CRP, adalimumab trough levels and antibodies to adalimumab). - To compare development of serious adverse events (SAEs) between interval extension and usual care.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18 or older • Diagnosis of colonic and/or distal ileal CD • Sustained steroid-free clinical remission for >12 months whilst being treated with adalimumab at a stable dose • Adalimumab dosed at 40 mg every 2 weeks • Full clinical response and disease control, all three criteria below need to be fulfilled prior to enrollment: - Absence of active inflammatory intestinal or extra-intestinal symptoms, as judged by both patient and physician - Fecal calprotectin (FC) < 150 µg/g and CRP <5 mg/L - Harvey Bradshaw Index (HBI) <5
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E.4 | Principal exclusion criteria |
• Absence of written informed consent • Concomitant corticosteroid usage • Need for IBD-related surgery • Actively draining peri-anal fistula • Pregnancy or lactation • Other significant medical conditions that might interfere with this study (such as current/recent malignancy, immunodeficiency syndromes and psychiatric illness) • Impossibility to measure outcomes, e.g. planned relocation, language issues, short life expectancy
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in cumulative incidence of persistent exacerbations (>8 weeks) between the dose reduction and usual care groups at 48-week follow-up. |
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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) |
• Cumulative incidence of patients with transient flare (duration ≤8 weeks) • Disease activity measured by Harvey-Bradshaw Index (HBI) and fecal calprotectin (FC) • PROM: PRO-2 (abdominal pain and stool frequency). • Adalimumab trough levels • Anti-adalimumab antibody levels • Adverse event rates (including injection site reactions and infections) • Quality of life (via SIBDQ) • Costs from a health care and societal perspective (via EQ-5D-5L, iMTA PCQ and iMTA MCQ) - (S)AE's
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will be seen every 3 months. |
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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 | 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 | 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 | 5 |
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 trial is ended when all patients had their last trial 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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |