E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to severely active ulcerative colitis. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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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 assess the efficacy and safety of adalimumab for the induction and maintenance of clinical remission in subjects with moderately to severely active ulcerative colitis. |
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics (PK) of adalimumab following subcutaneous administration. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female 18 years of age. 2. Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline. 3. Diagnosis of active ulcerative colitis confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy during the Screening Period, with exclusion of infection. 4. Active ulcerative colitis with a Mayo Score of 6-12 points and endoscopy subscore of 2-3 despite concurrent treatment with oral corticosteroids and/or immunosuppressants as defined below: ●Stable (± 5 mg) corticosteroid dose (prednisone of ³ 20 mg/day or equivalent) for at least 14 days prior to Baseline or maintenance corticosteroid dose (prednisone of ³ 10 mg/day and < 20 mg/day or equivalent) for at least 40 days prior to Baseline. ●At least a 90 day course of azathioprine or 6-MP prior to Baseline, with a dose of azathioprine ³ 1.5 mg/kg/day or 6-MP ³ 1 mg/kg/day (rounded to the nearest available tablet formulation), or a dose that is the highest tolerated by the subject (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time. Subject must be on a stable dose for at least 28 days prior to Baseline.
Concurrent therapy will not be required for subjects who were previously treated with corticosteroids or immunosuppressants (azathioprine or 6-MP) during the past 5 years and in the judgment of the investigator have failed to respond to or could not tolerate their treatment. 5. Subjects may be included if they have previously used an anti-TNF agent (except adalimumab) and discontinued its used due to a loss of response or intolerance to the agent. 6. Must be able to self-administer or has caregiver who can reliably administer subcutaneous injections. 7. Must be able and willing to give written informed consent and to comply with the requirements of this study protocol. 8. Female subjects must be either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion: ●Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD) ●Oral or parenteral contraceptives for 90 days prior to study drug administration ●A vasectomized partner The results of the serum pregnancy test performed at the Screening Visit and urine pregnancy test performed at the Baseline Visit must be negative. 9. Judged to be in generally good health by the investigator.
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E.4 | Principal exclusion criteria |
1. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or is planning bowel surgery. 2. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study. 3. Received cyclosporine, tacrolimus, mycophenolate mofetil, or methotrexate within 60 days prior to Baseline. 4. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 5. Received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to the Screening Visit and during the Screening Period. 6. Current diagnosis of fulminant colitis and/or toxic megacolon. 7. Subject with disease limited to the rectum (ulcerative proctitis). 8. Current diagnosis of indeterminate colitis. 9. Current diagnosis and/or history of Crohn's disease. 10. Currently receiving total parenteral nutrition (TPN). 11. Subject using aminosalicylates for less than 90 days prior to Baseline or not on a stable dose for at least 28 days prior to Baseline or discontinued use within 28 days of Baseline. 12. Subject with positive Clostridium difficlie (C. difficile) stool assay. 13. Subject who has previously used infliximab or any anti-TNF agent within 56 days of Baseline. 14. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded at any time ('primary non-responded') unless subject experienced a treatment limiting reaction. 15. Persistent chronic or active non-UC related infections requiring treatment with intravenous (iv) antibiotics, antivirals, or ntifungals within 30 days prior to Baseline or oral antibiotics, antivirals, or antifungals within 14 days prior to Baseline. 16. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy/flexible sigmoidoscopy shows evidence of dysplasia or a malignancy, subject may not be enrolled in the study. 17. History of listeria, histoplasmosis, chronic or active Hepatitis B infection, human immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system (CNS) demyelinating disease, or untreated tuberculosis (TB). 18. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study. There should be at least a 150-day period between the last dose of study drug and either conception or initiation of breast-feeding in women of childbearing potential. 19. Poorly controlled medical condition, such as uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accident and any other condition, which in the opinion of the investigator, would put the subject at risk by participation in the protocol. 20. Received any investigational agent within 30 days or 5 half lives prior to Baseline (whichever is longer). 21. History of clinically significant drug or alcohol abuse during the past year. 22. Subjects with known hypersensitivity to the excipients of adalimumab as stated in the label. 23. Subject with any prior exposure to Tysabri® (natalizumab). 24. Subject currently taking both budesonide and prednisone (or equivalent) simultaneously.
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E.5 End points |
E.5.1 | Primary end point(s) |
The co-primary efficacy endpoint is the proportion of subjects who achieve remission at Week 8 and proportion of subjects who achieve remission at 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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 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) | 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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
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 | Information not present in EudraCT |
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 |
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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.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |