Crohn's disease / Regional enteritis
Conditions
Interventions
Investigational Products: Adalimumab (40 mg/0.8 mL)
Double-Blind Induction:
Subjects will be randomized to receive one of 2 double-blind adalimumab
Induction Study regimens.
Doses:
(Higher Inducti
Sponsors
AbbVie Deutschland GmbH & Co. KG
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Males and females >= 18 and = 3 months prior to Baseline and confirmed by endoscopy during the Screening period or endoscopy performed within 45 days before Baseline, with exclusion of current infection, dysplasia, and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the Investigator, must be available. 3. Simplified Endoscopic Score for Crohn's Disease (SES-CD) >= 6, excluding the presence of narrowing component, or SES-CD >= 4, excluding the presence of narrowing component, for patients with disease limited to the ileum, on a screening endoscopy or endoscopy performed within 45 days before Baseline, confirmed by a central reader. 4. Crohn's Disease Activity Index (CDAI) >= 220 and 10 and = 6 mg/day, dose has been stable for at least 7 days prior to Baseline and the duration of the current steroid course has been at least 14 days prior to Baseline; * For subjects with a dose = 1.5 mg/kg/day or 6-MP >= 1 mg/kg/day (rounded to the nearest available tablet or half tablet formulation or a documented 6-TGN level of at least 230 pmol/8 × 108 RBC to clarify a therapeutic level was achived on the current dosing regimen) or MTX >= 15 mg/week (subcutaneous [SC]/Intramuscular [IM]), or a dose that is the highest tolerated by the subject (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time. Note: If a subject is taking both an oral corticosteroid and an immunosuppressant listed above, BOTH of the drugs need to meet the above criteria. Oral MTX use is allowed during the study (at a stable dose for 28 days prior to Baseline) however current or prior use of oral MTX is not sufficient for inclusion into the study. or, * Concurrent therapy with oral corticosteroids or immunosuppressants (azathioprine, 6-MP or SC/IM MTX) is not required for subjects not currently taking these medications who were previously treated during the past 1 year and have confirmed documentation of failure to respond, or were previously treated during the past 5 years and ha
Exclusion criteria
Exclusion criteria: 1. Subject with a current diagnosis of ulcerative colitis (UC) or indeterminate colitis. 2. Subject on azathioprine, 6-mercaptopurine (6-MP), methotrexate (MTX), or another immunosuppressant (e.g., thalidomide) who: * Has not been on these medications for at least 42 days prior to Baseline; or * Has not been on stable doses of these medications for at least 28 days prior to Baseline; or * Has discontinued these medications within 14 days of Baseline. 3. Subject on oral aminosalicylates who: * Has not been on stable doses of these medications for at least 28 days prior to Baseline; or * Has discontinued use of aminosalicylates within 14 days of Baseline. 4. Subject on oral corticosteroid > 40 mg/day (prednisone or equivalent) or subjects on budesonide > 9 mg/day; or * Subject taking an oral corticosteroid (excluding budesonide): o dose > 10 mg/day, but has not been on a stable dose for at least 7 days prior to Baseline; or o dose > 10 mg/day, but has not been on a current steroid course for at least 14 days prior to Baseline; or o dose = 6 mg/day, but has not been on a stable dose for at least 7 days prior to Baseline; or o dose >= 6 mg/day, but has not been on a current steroid course for at least 14 days prior to Baseline; or o dose < 6 mg/day dose but has not been on a stable dose of at least 10 days prior to Baseline; or o dose < 6 mg/day but the current course has not been at least 14 days in duration prior to Baseline; or Has been taking both oral budesonide and prednisone (or equivalent) simultaneously, with the exception of inhalers. 5. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 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 a symptomatic bowel stricture. 8. Subject with an abdominal or peri-anal abscess. 9. Subject with an ostomy or ileoanal pouch. 10. Subject who has short bowel syndrome. 11. Subject has received therapeutic enema or suppository, other than required for endoscopy, within 14 days prior to Screening and/or during the Screening period. 12. Subject with prior exposure to medications that have a potential or known association with progressive multifocal leukoencephalopathy (PML) including participation in a clinical trial of investigational agents targeting white cell trafficking (e.g., natalizumab [Tysabri®], rituximab [Rituxan®], efalizumab [Raptiva®]). Prior exposure to any anti-tumor necrosis factor (TNF) agent other than infliximab (including etanercept [Enbrel®], golimumab [Simponi®] or certolizumab pegol [Cimzia®]). Prior exposure to ustekinumab (Stelara®), tofacitinib (Xeljanz®) or vedolizumab (Entyvio®). 13. Subject who received any investigational agent or procedure within 30 days or 5 half-lives prior to Baseline, whichever is longer. 14. Subject who previously received treatment with adalimumab or previously participated in an adalimumab clinical study. 15. Subject receiv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy Endpoints: Subjects participating in the Induction Study randomized to the higher adalimumab induction dose regimen will be compared to those subjects randomized to the standard adalimumab induction regimen. Subject data from the Maintenance Study will be used for exploratory analyses. Co-Primary Induction Study Efficacy Endpoints: - Proportion of subjects who achieve a CDAI 50% SESCD from Baseline [or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline]) at Week 12. Pharmacokinetic: Blood samples will be collected for measurement of serum adalimumab concentration just prior to dosing at Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 26, Week 40, and Week 56/Premature Discontinuation and anti-adalimumab antibody (AAA) just prior to dosing at Baseline, Week 4, Week 12, Week 26, Week 40, and Week 56PD. Blood samples will also be collected for measurement of infliximab serum levels and Human Anti Chimeric Antibodies (HACA) just prior to dosing at Baseline. Exploratory Research Using Intestinal Mucosal Biopsy Samples (Optional): Optional intestinal biopsies will be collected with consent at Screening, Week 12, and Week 56 or at premature discontinuation. The purpose of these samples is to test potential biomarker signatures and new drug targets for IBD. Assessments will include but may not be limited to nucleic acids, proteins, metabolites or lipids. Safety: Safety analyses will be performed on all subjects who receive at least one dose of study drug. Incidence of adverse events, changes in vital signs, physical examination results, and clinical laboratory data will be assessed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Ranked Secondary Endpoints: 1. Proportion of subjects with sustained clinical remission (CDAI = 70 points from Baseline) at Week 4. 12. Proportion of subjects with clinical response (decrease in CDAI >= 70points from Baseline) at Week 12. 13. Proportion of subjects achieving response in IBDQ Bowel Symptom domain (increase of IBDQ bowel symptom domain score >= 8) at Week 4. 14. Proportion of subjects achieving response in IBDQ Bowel Symptom domain (increase of IBDQ bowel symptom domain score >= 8) at Week 12. 15. Proportion of subjects achieving response in IBDQ fatigue item (increase of IBDQ fatigue item score >= 1) at Week 12. Endpoints for Exploratory Maintenance Study: • Proportion of subjects who achieve endoscopic improvement (SES-CD | — |
Countries
Netherlands
Outcome results
None listed