Crohn syndrome regional enteritis
Conditions
Interventions
Sponsors
AbbVie Deutschland GmbH & Co. KG
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female >= 18 and = 3 months prior to Baseline and confirmed by endoscopy during the Screening Period or endoscopy performed within 15 days of the Screening Visit. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the Investigator, must be available. 3. Average daily liquid/very soft stool frequency score >= 2.5 or average daily abdominal pain score >= 2.0. 4. CDAI >= 220 and = 6 (or >= 4 for subjects with disease limited to the ileum), confirmed by a central reader. • A video-recorded ileocolonoscopy performed within 15 days prior to Screening can be used for the local and central reader assessment. 6. Subject has inadequately responded to or experienced intolerance to previous treatment with immunomodulators (e.g., azathioprine, 6-mercaptopurine, or methotrexate) and/or an anti-TNF agent (e.g., infliximab, adalimumab, or certolizumab pegol). The clinical measures that defined inadequate response should be based on the physician/investigator clinical assessment. Note: Criteria for inadequate response to or experienced intolerance to previous treatment with immunomodulator or an anti-TNF agent defined as: • Signs and symptoms of persistently active disease despite a history induction regimen with one of the following agents: o At least a consecutive 90-day course of azathioprine, 6-mercaptopurine or injectable MTX prior to Baseline, with a stable dose for at least 28 days prior to Baseline of azathioprine >= 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 or higher 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. At least one 6-week induction with Infliximab: 5 mg/kg IV, 3 doses at least 2 weeks apart o At least one 4-week induction with Adalimumab: one 160 mg SC dose (or 80 mg SC dose in approved countries) followed by one 80 mg SC dose (or 40 mg SC dose in approved countries) followed by one 40 mg dose at least 2 weeks apart o At least one 4-week induction with Certolizumab pegol: 400 mg SC, 2 doses at least 2 weeks apart OR • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify) OR • History of intolerance of at least one TNF antagonist (including, but not limited to infusion related reaction, demyelination, congestive heart failure and infection) 7. Subject has a negative tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of anti-TB prophylaxis, prior to Baseline.
Exclusion criteria
Exclusion criteria: colitis. 2. Subject with previous exposure to JAK inhibitor (e.g., tofacitinib, baricitinib). 3. Subjects who discontinued biologic therapy such as Infliximab (REMICADE), Certolizumab pegol (CIMZIA), Adalimumab (HUMIRA), Vedolizumab (ENTYVIO), Natalizumab (TYSABRI) 30 mg/day within 7 days of Baseline; • Is receiving budesonide > 9 mg/day within 7 days of Baseline; • Has discontinued use of corticosteroid within 7 days of Baseline; • Has not been on stable doses of corticosteroid for at least 7 days prior to Baseline; or • Has been taking both oral budesonide and prednisone (or equivalent) simultaneously. 7. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 8. Subject on probiotics who has not been on stable dose for at least 14 days prior to Baseline. 9. Subject who previously or currently use Crohn's disease related antibiotics and meets one of the following criteria: • Has not been on stable doses for at least 14 days prior to Baseline; • Has discontinued Crohn's disease related antibiotics within 14 days of Baseline. 10. Subject received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline. 11. Subject has received therapeutic enema or suppository, other than required for endoscopy, within 7 days prior to Screening and/or during the Screening Period. 12. Subject who has had surgical bowel resection within the past 6 months or is planning any resection while enrolled in the study. 13. Subject with an ostomy, ileoanal pouch or symptomatic bowel stricture. 14. Subject with an abdominal or peri-anal abscess. 15. Subject who has short bowel syndrome. 16. Subject who previously received stem cell transplantation or Subject who previously received fecal microbial transplantation in the past 1 month. 17. Subject who received non-steroidal anti-inflammatory drugs (NSAIDs) (except topical NSAIDs and the use of low dose aspirin for cardiovascular (CV) protection) within 14 days prior to Screening and during the Screening Visit. 18. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit. 19. Subject currently receiving total parenteral nutrition (TPN) or plan to receive TPN at any time during the course of the study. 20. Subject with positive Clostridium difficile (C. difficile) toxin stool assay during the Screening Period. 21. Screening laboratory and other analyses show any of the following abnormal results: • Serum Aspartate Transaminase (AST) or Alanine transaminase (ALT) > 21.5 × upper limit of the reference range (ULN); • Estimated glomerular filtration rate by simplified 4-variable Modificatio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endpoint Definitions: The following definitions apply to the efficacy variables described below: • Remission: Endoscopic remission AND Clinical remission • Response: Endoscopic response AND Clinical response • Endoscopic remission: SES-CD 1 in any individual variable • Endoscopic response: SES-CD at least 25% reduction from baseline • Clinical remission: average daily stool frequency | — |
Secondary
| Measure | Time frame |
|---|---|
| The co-primary endpoints are: • Proportion of subjects who achieve endoscopic remission at Week 12/16. • Proportion of subjects who achieve clinical remission at Week 16. The secondary endpoints (Double-Blind Induction Treatment Period) include: • Proportion of subjects who achieve CDAI = 70 points from Baseline at Week 16. • Proportion of subjects who achieve clinical remission at Week 12. • Proportion of subjects who achieve remission at Week 16 (endoscopic remission at Week 12/16 and clinical remission at Week 16). • Proportion of subjects who achieve response at Week 16 (endoscopic response at Week 12/16 and clinical response at Week 16). • Proportion of subjects with endoscopic response at Week 12/16. • Proportion of subjects who achieve clinical response at Week 16. • Proportion of subjects with an average daily SF >= 2.5 AND average daily AP >= 2.0 at Baseline who achieve clinical remission at Week 16. • Proportion of subjects taking corticosteroids at Baseline who discontinued corticosteroid use and achieve CDAI = 70 points from Baseline at Week 52. • Change from Baseline in fecal calprotectin level at Week 52. • Change from Baseline in hs-CRP at Week 52. • Change in IBDQ from Baseline at Week 52. • Proportion of subjects with isolated ileal Crohn's disease who achieve remission at Week 52. • Change in EIMs from Baseline at Week 52. Additional endpoints include assessment of the above endpoints over time. | — |
Countries
The Netherlands
Outcome results
None listed