A Multicenter Randomized, Open-label Study to Compare the Efficacy of Subcutaneous Infliximab Monotherapy With Subcutaneous Infliximab and Concomitant Immunosuppression in the Treatment of Moderate to Severe Crohn's Disease

NL76663.018.21

Study Design: A Prospective Multicenter Randomized Controlled, Open-label Non-inferiority Study to Investigate the Efficacy of Subcutaneous (SC) Infliximab (IFX) with and without Immunomodulators during Induction treatment in Moderate to Severe Crohn's Disease. Primary endpoint: The proportion of patients in corticosteroid-free clinical remission (as defined by a Crohn's disease activity index (CDAI)\<150) and endoscopic response (as defined by a simple endoscopic score for Crohn's disease (SES-CD) drop of at least 50%) at week 26. Accrual and feasibility: This study will enroll 158 subjects at approximately 20 sites in the Netherlands (peripheral and academic hospitals). The estimated enrollment is 0.5 patient/centre/month leading to an inclusion duration of 16 months once all centres are open. The first enrolment is anticipated in Q1 2021. Treatment, dosage and administration: Eligible patients will be randomized to receive SC IFX monotherapy (240mg at week 0 and week 2 and then 120mg every other week (EOW) OR SC IFX (240mg at week 0 and week 2 and then 120mg EOW) in combination with immunosuppression.

2021-11-25

2024-01-01

2024-07-01

Recruiting

Early phase I

158

Inclusion Criteria: 1. Patients 18 years or older diagnosed with Crohn's disease 2. Patients with moderate to severely active Crohn's disease with a Crohn's Disease Activity Index (CDAI) of 250 to 450 and presence of endoscopic ulceration in the terminal ileum, colon or both. Minimal SES-CD is ≥ 6 or ≥ 4 for isolated ileal disease. 3. Patients who had no response or loss of response to or have had intolerable side effects to one or more to the following: glucocorticoids, thiopurines (azathioprine/6-mercaptopurine/6-thioguanin), methotrexate , adalimumab, vedolizumab or ustekinumab OR patients in need of immediate top-down treatment with IFX at the discretion of the treating physician. 4. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 5. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure. 6. Male or non-pregnant, non-lactating females. No wish to become pregnant in the coming 26 weeks. Exclusion Criteria: 1. Patients at imminent need of surgery as judged by the treating clinician 2. Patients with the short bowel syndrome, an ostomy or a symptomatic non-inflammatory stricture 3. Patients previously exposed to IFX (intravenous or subcutaneous) 4. Previously unacceptable side effects or intolerance to all immunosuppressants (both thiopurines and methotrexate) 5. Treatment with adalimumab or vedolizumab or ustekinumab within 30 days 6. Patients who have had a primary non-response to adalimumab or had intolerable class-related side effects (as evaluated at the discretion of the treating physician) 7. Enteric pathogens (such as Salmonella, Shigella, Yersinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening 8. Ongoing participation in another interventional trial 9. Patients with Ulcerative Colitis or Inflammatory bowel disease unclassified (IBD-U) 10. Patients with ongoing abdominal or undrained perianal abscess 11. Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma, which has been removed 12. Active or latent tuberculosis (screening according to national guidelines). Except when the latter has been treated appropriately according to national guidelines. 13. Cardiac failure in the New York heart Association (NYHA) stage III-IV 14. History of demyelinating disease 15. Recent live vaccination (≤ 4 weeks) 16. Patients with ongoing acute/chronic infection (including but not limited to HIV, hepatitis B and C) with the exception of chronic herpes labialis or cervical human papillomavirus (HPV) 17. History of cancer in the last 5 years with the exception of non-melanoma skin cancer 18. Male patients with Epstein-Barr virus (EBV) negative serology 19. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures 20. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures 21. Patients unable to attend all study visits 22. Patients with a history of non-compliance with clinical study protocols 23. Contraindication for endoscopy 24. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer 25. Pregnancy or lactation or wish to become pregnant in the coming 26 weeks

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "Prospective Multicenter Randomized Controlled, Open-label Non-inferiority Study to Investigate the Efficacy of Subcutaneous Infliximab with and without Immunomodulators during Induction treatment in Moderate to Severe Crohn's Disease.", 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 158, 'type': 'ESTIMATED'}}

2023-09-29