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 |
The primary objective of this study is to assess the efficacy and safety of two adalimumab induction regimens in achieving clinical remission (CDAI < 150) at Week 4 and endoscopic response defined as decrease in SES-CD > 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline) at Week 12, in subjects with moderately to severely active Crohn's disease and evidence of mucosal ulceration at Baseline.
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E.2.2 | Secondary objectives of the trial |
• To assess the safety and efficacy of two adalimumab induction regimens in reducing signs and symptoms of Crohn's disease at Week 12. • To assess the efficacy and safety of two adalimumab maintenance regimens in reducing signs and symptoms of Crohn's disease at Week 56. • To assess pharmacokinetics (PK) and immunogenicity of two adalimumab induction regimens following subcutaneous (SC) administration.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1)Subject is between the ages of 18 to 75 years 2) Diagnosis of Crohn's disease (CD) for at least 90 days, confirmed by endoscopy during the Screening Period or endoscopy performed within 45 days before Baseline. 3) Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 at Baseline despite concurrent or prior treatment with a full oral corticosteroids and/or immunosuppressants
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E.4 | Principal exclusion criteria |
1) Subject with ulcerative colitis or indeterminate colitis 2) Subject who has had surgical bowel resections within the past 6 months or is planning resection 3) Subject with an ostomy or ileoanal pouch 4) Subject with bowel stricture or abdominal or peri-anal abscess 5) Subject who has short bowel syndrome 6) Chronic recurring infections or active TB |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who achieve clinical remission at Week 4 and proportion of subjects with endoscopic response (decrease > 50% SES-CD from Baseline [or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline]) at Week 12. |
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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 subjects with clinical remission at weeks 4 and 12 • Proportion of subjects with CDAI < 150 at Week 4 and endoscopic response at Week 12 • Proportion of subjects with clinical remission at week 12 • Among subjects on corticosteroids at baseline, proportion of subjects who discontinued corticosteroid use and achieved clinical remission at week 12 • Proportion of subject with endoscopic remission (SES-CD ≤ 4 and at least a 2 point reduction versus baseline and no subscore greater than 1 in any individual variable) at Week 12 • Change from Baseline in fecal calprotectin level at Week 4. • Proportion of subjects with hs-CRP < 5 mg/L and fecal calprotectin < 250 µ/g at Week4. • Proportion of subjects with CDAI < 150, hs-CRP < 5 mg/L, and fecal calprotectin 250 µg/g at Week 4. • Proportion of subjects with CDAI < 150, hs-CRP < 5 mg/L, SES-CD ≤ 4 and at least a 2 point reduction versus baseline and no subscore greater than 1 in any individual variable, and fecal calprotectin < 250 µg/g at Week 12. • Proportion of subjects who achive an SES-CED ≤ 2 at Week 12. • Proportion of subjects with clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 4. • Proportion of subjects with clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 12. • Proportion of subjects achieving response in IBDQ Bowel Symptom domain (increase of IBDQ bowel symptom domain score ≥ 8) at Week 4. • Proportion of subjects achieving response in IBDQ Bowel Symptom domain (increase of IBDQ bowel symptom domain score ≥ 8) at Week 12. • Proportion of subjects achieving response in IBDQ fatigue item (increase of IBDQ fatigue item score ≥ 1) at Week 12. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 4 and 12 depending on 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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 |
two adalimumab induction and maintenance regimens are compared |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
European Union |
Israel |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |