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 | 18.1 |
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 efficacy, safety and pharmacokinetics after dose escalation for the subjects who lost response to adalimumab in Japanese patients with Crohn's disease. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject ≥ 15 years of age at the time of informed consent.
Subject with Crohn's disease who received induction treatment of commercially available Humira® (160 mg initially and 80 mg at 2 weeks after initial dose), achieved CR-70 at 4 weeks after initial dose, and then lost response during maintenance treatment with Humira® 40 mg eow.
– Definition of lost response: increased CDAI ≥ 50 compared to the timepoint with lowest CDAI score after initiation of Humira® treatment and absolute CDAI score ≥ 200
– Subject must satisfy the definition of lost response at both Screening and Week 0.
Subject with CRP ≥ 1 mg/dL at Screening.
If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and for 150 days after the last dose of study drug.
Subject has a negative TB Screening Assessment. If the subject has evidence of a latent TB infection; the subject must initiate and complete a minimum of 21 days of an ongoing TB prophylaxis (in such case, screening period can be prolonged until 21 days past after initiation of prophylaxis and study drug is administered) or have documented completion of a full course of TB prophylaxis, prior to Week 0. |
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E.4 | Principal exclusion criteria |
Subject with suspicion of colitis other than Crohn's disease.
Subject with an ostomy or ileoanal pouch. (Subjects with a previous ileo-rectal anastomosis are not excluded).
Subject using oral corticosteroid not on a stable for at least 14 days prior to Week 0 or discontinued use within 14 days of Week 0, or received injection of corticosteroids (other than topical use) within 28 days of Week 0.
For subject using immunomodulators (AZA, 6-MP or MTX), initiated those within 90 days of Week 0 or not on a stable dose for at least 28 days prior to Week 0 or discontinued use within 28 days of Week 0.
Subject with abscess or suspicion of abscess, or subject with infection(s) requiring treatment with intravenous (iv) anti-infectives within 28 days prior to Week 0 or oral anti-infectives within 14 days prior to Week 0. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the proportion of the subjects who achieved CR-50 (CDAI decrease ≥ 50 from Week 0) at Week 8. |
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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) |
1) Proportion of the subjects who achieved remission (CDAI < 150) at each visit
2) Proportion of the subjects who achieved CR-50 at each visit (Week 8 is primary endpoint)
3) Proportion of the subjects who achieved CR-70 (CDAI decrease from Week 0 ≥ 70) at each visit
4) Proportion of the subjects who achieved CR-100 (CDAI decrease from Week 0 ≥ 100) at each visit
5) Change in CRP from Week 0 at each visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 4 Weeks up to Week 52 |
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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 | 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 | No |
E.6.10 | Pharmacogenetic | No |
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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |