| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe Crohn's Disease (Harvey Bradshaw Index score greater or equal to7). |
|
| 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 | 10013099 |
| E.1.2 | Term | Disease Crohns |
|
| 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 evaluate and delineate the safety and efficacy profile of adalimumab (Humira pre-filled syringe or Humira pre-filled PEN) when administered to subjects with moderate to severe Crohn's Disease. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Diagnosis of moderate to severe Crohn's Disease confirmed by endoscopy or radiologic evaluation for greater than 4 months (16 weeks).
2. Inadequate response to conventional therapy for Crohn's Disease in the opinion of and as documented by the treating physician.
3. Harvey Bradshaw Index score greater or equal to 7.
4. Males and females greater or equal to 18 and less than or equal to 75 years of age at the Baseline visit.
5. If female, subject is either not of child bearing potential, defined as post menopausal for at least (1) year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control during the study and for 150 days after the last dose:
·Condoms, sponge, foam, jellies, diaphragm, intrauterine device, subdermal implantation
·Oral or parenteral contraceptives (including hormonal vaginal devices and transdermal patches) for three months prior to study drug administration
·A vasectomized partner
6.If female, subject is not breast-feeding throughout the study and for 150 days after the last dose.
7. Subject or his/her legal representative has voluntarily signed and dated an informed consent approved by and compliant with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
8. Adequate cardiac, renal and hepatic function as determined by the principal investigator and demonstrated by Screening laboratory evaluations, questionnaires, and physical examination results that are within normal limits.
9. Subjects must be able to self-inject study medication or have a designee or healthcare professional who can inject the study medication.
|
|
| E.4 | Principal exclusion criteria |
1. History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma − in-situ of the cervix.
2. History of listeria, human immunodeficiency virus (HIV), chronic or active Hepatitis B, an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease or active TB.
3. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
4. Subject with symptomatic known obstructive strictures.
5. Subjects with abscess or suspicion of abscess, defined as fever and/or anal pain.
6. Subject who has had surgical bowel resections within the past 6 months or is planning any resection at any time point while enrolled in the study.
7. Subject with an ostomy or ileoanal pouch.
8. Subject who has short bowel syndrome as determined by the investigator.
9. Subject who is currently receiving total parenteral nutrition (TPN).
10. Females who are pregnant or will not discontinue breast-feeding.
11. Subject who has received any investigational chemical agent in the past 30 days or 5 half-lives prior to Baseline (whichever is longer).
12. Subject who has received any investigational biological agent within 5 half-lives prior to Baseline.
13. Subject who has an active infection or has had systemic antibiotic, antiviral, or antifungal treatment within 3 weeks prior to Baseline for infection. Subjects are allowed to be on ciprofloxacin or metronidazole for their non-infectious Crohn's symptoms.
14. Subject with a history of clinically significant drug or alcohol abuse in the last year.
15. Subjects with a poorly controlled medical condition such as: uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or the sponsor, would put the subject at risk by participation in the protocol.
16. Subjects with positive C. difficile stool assay.
17. Subject who has previously used infliximab or any anti-TNF within 8 weeks of Baseline.
18. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
19. Screening laboratory and other analyses show any of the following abnormal results:
● Electrocardiogram (ECG) - with clinically significant abnormalities;
● Aspartate transaminase (AST) or alanine transaminase (ALT) >1.75 x the upper limit of the reference range;
● Total bilirubin greater or equal to 3 mg/dL;
●Serum creatinine >1.6 mg/dL;
20. Subjects on Imuran® (azathioprine), 6 MP, or MTX who have not been on stable doses of these medications for at least 4 weeks prior to Baseline. Additionally, for subjects on those medications, subjects must have been on azathioprine, 6 MP, or MTX for at least 12 weeks prior to Baseline. Moreover, subjects who have been on azathioprine, 6 MP, or MTX who have discontinued these medications within 12 weeks of Baseline are excluded.
21. Subjects on aminosalicylates, mesalamine, sulfasalazine, or Crohn's related antibiotics who have not been on stable doses of these medications for at least 4 weeks prior to Baseline. In addition, subjects on aminosalicylates, sulfasalazine or Crohn's related antibiotics who have discontinued these medications within 4 weeks of Baseline are excluded.
22. Subjects on prednisone >40 mg/day (or equivalent) and subjects who were not on stable doses for two weeks prior to Baseline. In addition, subjects who discontinued prednisone (or equivalent) within 2 weeks of Baseline are excluded.
23. Subjects on budesonide >9 mg/day and subjects who were not on stable doses of budesonide for at least 2 weeks prior to Baseline. In addition, subjects who discontinued budesonide within 2 weeks of Baseline are excluded.
24. Subjects currently taking both budesonide and prednisone (or equivalent) are excluded.
25. Subjects who have been on cyclosporine (iv, oral), tacrolimus (any form) or Mycophenolate mofetil within 8 weeks of Baseline are excluded.
26. Subjects with any prior exposure to Tysabri® (natalizumab).
27. Subjects with known hypersensitivity to the excipients of adalimumab as stated in the label.
28. Subject is not in compliance with Prior Therapy requirements |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety endpoints will include assessments of adverse events, laboratory data, physical exams and vital signs throughout the study.
Efficacy Endpoints are changes in Harvey-Bradshaw Index total score, SIBDQ, and WPAI assessed from Baseline to Weeks 2, 4, 8, 12 and 20. For efficacy evaluation, the Harvey-Bradshaw Index total score, assessment of draining fistulas, SIBDQ, WPAI, assessment of extra-intestinal manifestations and unscheduled outpatient visits, emergency room visits and hospitalization. Each variable will be assessed at Weeks 2, 4, 8, 12 and 20.
|
|
| 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 | 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 | No |
| 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 33 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 200 |
| 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 |
|
| 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
|
| last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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