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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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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 |
Induction Study – Evaluate the efficacy and safety of a higher induction dose regimen of adalimumab versus standard induction dosing in inducing clinical revision at week 8 in subjects with moderately to severely active UC
Maintenance Study – Evaluate safety and efficacy of 44 weeks of three maintenance dosing regimens of adalimumab in achieving clinical remission at week 52 (from the Induction Study Baseline) in subjects with moderately to severely active UC who achieved clinical response at week 8 of the Induction Study. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
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E.3 | Principal inclusion criteria |
1)Subject is between the ages of 18 to 75 years
2) Diagnosis of UC for at least 90 days, confirmed by endoscopy (colonoscopy or flexible sigmoidoscopy) during during the Screening Period
3) Active ulcerative colitis with a Mayo Score of 6 – 12 points and endoscopy subscore of 2 – 3 despite concurrent treatment with oral corticosteroids or immunosuppressants or both |
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E.4 | Principal exclusion criteria |
1. Subject with Crohn's disease (CD) or indeterminate colitis (IC).
2. Current diagnosis of fulminant colitis and/or toxic megacolon.
3. Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
4. Chronic recurring infections or active TB |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for the Induction Study is: Proportion of subjects achieving clinical remission (defined as a Full Mayo score ≤ 2 with no subscore > 1) at Week 8.
The primary efficacy variable for the Maintenance Study is: Proportion of Week 8 responders (per Full Mayo score, defined as a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore [RBS] ≥ 1 or an absolute RBS of 0 or 1) achieving clinical remission (per Full Mayo score) at Week 52. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 8 for Induction Study, Week 52 for Maintenance Study |
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E.5.2 | Secondary end point(s) |
Secondary efficacy variables for the Induction Study are:
● Proportion of subjects achieving endoscopic improvement (endoscopic subscore of 0 or 1) at Week 8.
● Proportion of subjects with fecal calprotectin below 150 mg/kg at Week 8.
● Proportion of subjects with IBDQ response (increase of IBDQ ≥ 16 from Baseline) at Week 8.
● Proportion of subjects achieving clinical response (per Full Mayo score) at Week 8.
● Proportion of subjects achieving endoscopic subscore of 0 at Week 8.
Secondary efficacy variables for the Maintenance Study are:
● Proportion of Week 8 responders (per Full Mayo score) achieving endoscopic improvement (endoscopic subscore of 0 or 1) at Week 52.
● Proportion of Week 8 responders (per Full Mayo score) taking steroids at Baseline who are steroid-free for at least 90 days at Week 52.
● Proportion of Week 8 responders (per Full Mayo score) taking steroids at Baseline who are steroid-free for at least 90 days and in clinicalremission (per Full Mayo score) at Week 52.
● Proportion of Week 8 remitters (per Full Mayo score) achieving clinical remission (per Full Mayo score) at Week 52.
● Proportion of Week 8 remitters (per Full Mayo score) achieving endoscopic improvement (endoscopic subscore of 0 or 1) at Week 52.
● Proportion of Week 8 remitters (per Full Mayo score) taking steroids at Baseline who are steroid-free for at least 90 days at Week 52.
● Proportion of Week 8 remitters (per Full Mayo score) taking steroids at Baseline who are steroid-free for at least 90 days and in clinical remission (per Full Mayo score) at Week 52.
● Proportion of Week 8 responders (per Full Mayo score) with IBDQ response (increase of IBDQ ≥ 16 from Baseline) at Week 52.
● Proportion of Week 8 non-responders (per Full Mayo score) with clinical remission (per Full Mayo score) at Week 52.
● Proportion of Week 8 non-remitters (per Full Mayo score) with clinical remission (per Full Mayo score) at Week 52.
● Proportion of Week 8 responders (per Full Mayo score) achieving endoscopic subscore of 0 at Week 52.
● Proportion of Week 8 remitters (per Full Mayo score) achieving endoscopic subscore of 0 at Week 52. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
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 |
Other doses of adalimumab |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Israel |
Japan |
Switzerland |
United States |
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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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The end of study is defined as the date of the Last subject last visit, or the last follow-up contact, whichever is longer. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 4 |