| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10011401 |
|
| 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 that tight control of disease activity using stringent criteria based on CDAI, hs-CRP, fecal Calprotectin, and corticosteroid use improves the rate of mucosal healing at Week 56, as compared to management using less stringent criteria based on CDAI and corticosteroid use. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the pharmacokinetics (PK) of adalimumab following subcutaneous administration. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Males and females ≥ 18 and ≤ 75 years of age at the Baseline visit. 2. Diagnosis of colonic or ileocolonic CD confirmed using imaging technology or endoscopy not more than 4 years prior to Baseline. 3. CDAI score of ≥ 220 and ≤ 450 at the Baseline visit. 4. Sum of deep ulcerations, superficial ulcerations, surface involved by disease, surface involved by ulceration CDEIS (Crohn`s disease Endoscopic Index of Severity)subscores in at least one non ileal segment > 6, with presence of ulcers, AND total CDEIS > 8, at the Screening visit. 5. hs-CRP ≥ 5 mg/L at the Screening visit. 6. Fecal Calprotectin ≥ 250 μg/g at the Screening visit. 7. 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 and foam, jellies with diaphragm or intrauterine device (IUD). IUDs may fail during azathioprine treatment. Alternative or additional contraceptive measures are advised, if azathioprine is initiated. • Oral or parenteral contraceptives for 3 months prior to study drug administration. • A vasectomized partner. 8. Male subjects must agree to use an acceptable form of birth control, listed above at the start of azathioprine administration and for 90 days after last dose of azathioprine. Males should also commit to inform his partner(s) about it and to report any pregnancy to the investigator. 9. If female, subject is not breast-feeding throughout the study and for 150 days after last dose. 10. Subjects or his/her legal representative have 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). 11. Adequate cardiac, renal and hepatic function as determined by the Principal Investigator and demonstrated by Screening laboratory evaluations, questionnaires and physical examination results that do not indicate an abnormal clinical condition which would place the subject at undue risk and thus preclude subject participation in the study. 12. Subjects must be able to self-inject and orally administer study medication or have a designee or Healthcare Professional who can assist. |
|
| E.4 | Principal exclusion criteria |
| •Previous or current biologic use for Crohn`s disease or participation in a biologic study. • Previous or current use of immunomodulators for Crohn`s disease or participation in an immunomodulator study. •Systemic corticosteroid or budesonide use for Crohn`s disease within 6 months of Screening. •Greater than one previous course of corticosteroid (systemic corticosteroid or budesonide). •Systemic corticosteroid or budesonide use for Crohn`s disease in the previous 2 years before Screening for > 6 months. •Subjects not on stable doses of aminosalicylates, or CD-related antibiotics for at least 4 weeks prior to Baseline. Subject must consent to remain on stable doses throughout the entire trial. •Subjects on topical therapy for Crohn`s disease. •Deficient or low Thiopurine methyltransferase (TPMT) activity (≤ 67mU/L). •Montreal Classification B3 or Montreal classification B2 with symptoms of obstruction. •Stricturing on ileocolonoscopy at Screening regardless of symptoms. •Greater than one major surgery for Crohn`s disease in the medical history, or planned surgery for Crohn`s disease. •History of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix. 1•History of listeriosis, histoplasmosis, human immunodeficiency virus (HIV), chronic or active Hepatitis B, an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease (including myeletis), neurologic symptoms suggestive of demyelinating disease, chronic recurring infection, active TB (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections. PPD test positive at Screening ≥ 5 mm. • Subjects with a current diagnosis of ulcerative colitis or indeterminate colitis as determined by the Investigator and Abbott Medical Monitor. •Subjects with an ostomy, or ileoanal pouch (subject with previous ileo-rectal anastomosis are not excluded), draining fistula, abscess. • Subjects who have short bowel syndrome as determined by the Investigator. •Subjects who are currently receiving total parenteral nutrition (TPN) or enteral nutrition via a tube for complete nutrition. •Females who are pregnant, considering becoming pregnant or will not discontinue breast feeding. •Subjects who have received any investigational chemical or biological agent in the past 30 days or 5 half-lives prior to Baseline (whichever is longer). •Subjects who have had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Baseline for all non–Crohn`s-related infections. •Subjects with a history of clinically significant drug or alcohol abuse in the last year. •Subjects with a poorly controlled medical condition or with positive C. difficile stool assay at Screening. • Screening laboratory and other analyses show any of the following abnormal results: Electrocardiogram (ECG) – with clinically significant abnormalities; AST or ALT > 2 � the upper limit of the reference range; Total bilirubin ≥ 3 mg/dL; Serum creatinine > 1.6 mg/dL. •Subjects who have undergone therapeutic enemas within 2 weeks prior to Baseline or who have been on cyclosporine (intravenous, oral), tacrolimus or Mycophenolate mofetil or with known hypersensitivity to the excipients of adalimumab as stated in the label. • Subjects with a previous history of dysplasia of the gastrointestinal tract, or found to have dysplasia in any biopsy performed during the Screening endoscopy. •Subjects that took non-steroidal anti-inflammatory drugs (NSAIDS) within 14 days prior to Screening. •Current use of allopurinol. • Subjects with a contraindication to an MRI •Impaired renal function at screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is the proportion of subjects with mucosal healing (CDEIS < 4) and no deep ulcerations on ileocolonoscopy (absence of all deep ulcerations in all segments explored in CDEIS) at Week 56. |
|
| 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 | 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 |
|
| 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 | Yes |
| 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 | 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 |
| diverso algoritmo di trattamento |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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