| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Crohn's Disease |
|
| 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 | 10011401 |
| E.1.2 | Term | Crohn's disease |
|
| 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 demonstrate the safety and efficacy of adalimumab and to assess the pharmacokinetics (PK) of adalimumab administered by SC injection in pediatric subjects with moderate to severe CD. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects between the ages of 6 and 17, inclusive prior to Baseline dosing.
2. Subjects with a diagnosis of CD for greater than 12 weeks prior to Screening, confirmed by endoscopy or radiologic evaluation.
3. PCDAI score of > 30 despite concurrent treatment with an oral corticosteroid, and/or azathioprine or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined on page 27 of the study protocol.
4. If female, subjects who are sexually active and are of child-bearing potential should be practicing an approved method of birth control throughout the study and for 150 days after study completion. Examples of approved methods of birth control include the following:
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD)
● Oral, parenteral or intravaginal contraceptives for 12 weeks prior to study drug
administration
● A vasectomized partner
5. Parent or legal guardian as required has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject's parent or legal guardian has had the opportunity to ask questions. Subjects will be included in all discussions in order to obtain verbal/and or written assent.
6. Adequate cardiac, renal and hepatic function as determined by the principal investigator and demonstrated by Screening laboratory evaluations and physical examination results that are within normal limits.
7. Parent or legal guardian must be willing to actively supervise storage and administration of study drug and to ensure that the time of each dose is accurately recorded in the subject's diary.
8. For subjects that have previously received infliximab, the subjects must have had an initial response and then discontinued use due to a loss of response or must have discontinued use due to intolerance to the medication (see Appendix A for definitions). |
|
| 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, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV) infection, any immunodeficiency syndrome, central nervous system (CNS) demyelinating disease or active TB (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections.
3. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the investigator and Medical Monitor.
4. Subject with symptomatic known obstructive strictures.
5. Subject who has had surgical bowel resections within the past 24 weeks of the Baseline visit or is planning any resection at any timepoint while enrolled in the study.
6. Subject with an ostomy or ileoanal pouch. (Subjects with a previous ileo-rectal anastomosis are not excluded).
7. Subject who has short bowel syndrome as determined by the investigator.
8. Subject who is currently receiving total parenteral nutrition (TPN).
9. Females who are pregnant or are currently breast-feeding.
10. Subject who has received any investigational chemical agent in the past 30 days or 5 half-lives prior to Baseline (whichever is longer).
11. Subject who has received any investigational biological agent in the past 16 weeks or 5 half-lives prior to Baseline (whichever is longer).
12. Subject who has had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Baseline for all non-Crohn's related infections.
13. Subject with a history of clinically significant drug or alcohol abuse in the last year.
14. Subjects with a poorly controlled medical condition such as: uncontrolled diabetes, recurrent infections, unstable ischemic heart disease, moderate to severe 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.
15. Subjects with positive C. difficile stool assay.
16. Subject who has previously used infliximab within 8 weeks of Baseline.
17. Subject who has previously used infliximab and has not clinically responded at any time ("primary non-responder") unless subject experienced a treatment limiting reaction to infliximab.
18. Previous treatment with any other anti-TNF agent except infliximab.
19. Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.
20. Screening laboratory and other analyses show abnormal results. (Please see page 31 of the study protocol for details).
21. Subjects on azathioprine, 6 MP, or MTX who have not been on these medications for at least 8 weeks prior to Baseline and on stable doses of these medications for at least 4 weeks prior to Baseline. Subjects who have been on azathioprine, 6 MP, or MTX who have discontinued these medications within 8 weeks of Baseline.
22. Subjects on aminosalicylates, or Crohn's-related antibiotics (fluoroquinolones such as ciprofloxacin or nitroimidazole derivatives such as metronidazole) who have not been on stable doses of these medications for at least 4 weeks prior to Baseline. In addition, subjects on aminosalicylates or Crohn's-related antibiotic treatments who have discontinued these medications within 4 weeks of Baseline.
23. Subjects on prednisone > 40 mg/day (or equivalent) or subjects on < 10 mg/day prednisone and subjects who were not on a stable dose for at least two weeks prior to Baseline. In addition, subjects who discontinued prednisone (or equivalent) within two weeks of Baseline.
24. Subjects on growth hormone who have not been on a stable dose for at least 12 weeks prior to Baseline. Subjects must consent to remain on a stable dose through the duration of the study.
25. Subjects on budesonide > 9 mg/day and subjects who were not on stable doses for at least 2 weeks prior to Baseline. In addition, subjects who discontinued budesonide within 2 weeks of Baseline.
26. Subjects currently taking both budesonide and prednisone (or equivalent).
27. Subjects who have undergone therapeutic enemas within 2 weeks prior to Baseline.
28. Subjects who have been on cyclosporine (intravenous [IV], oral), tacrolimus (any form), or mycophenolate mofetil within 28 days of Baseline.
29. Subjects who have been on Kineret (Anakinra) must discontinue use 2 days prior to Baseline.
30. Subjects with any prior exposure to Tysabri (natalizumab).
31. Subjects with known hypersensitivity to the excipients of adalimumab as stated in the label.
32. Subjects with a previous history of dysplasia of the gastrointestinal tract.
33. Subjects that weigh < 17 kg at Screening.
34. Subject is not in compliance with Section 5.2.3 (Prior and Concomitant Therapy). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficay endpoint for this study is the proportion of subjects who are in clinical remission at Week 26, as measured by the PCDAI in the ITT population. PCDAI clinical remission is defined as PCDAI score less than or equal to 10. |
|
| 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 | 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 | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Double-blind study with open-label induction regimen. Parallel group dosing according to body weight |
|
| 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 |
| Different dose of the same IMP |
|
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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 | Yes |
| 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
|
|
| 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 | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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