None listed
Conditions
Interventions
Biological/Vaccine, Non-Stem Cell : Patients with moderate to severe Crohn's disease will be randomized in a 1:1 ratio to receive either subcutaneous infliximab monotherapy or combination therapy wi
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients 18 years or older diagnosed with Crohn’s disease (19 years or older in the case of South Korea) 2.Patients with moderate to severely active Crohn’s disease with a Crohn’s Disease Activity Index (CDAI) of 220 to 450 and presence of endoscopic ulceration in the terminal ileum, colon or both. Minimal SES-CD is = 6 (colonic or ileocolonic disease) 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-mercaptopurin/6-thioguanin), methotrexate , adalimumab, vedolizumab or ustekinumab OR patients in need of immediate top-down treatment with infliximab at the discretion of the treating physician. 4.In the opinion of the investigator, the subject who 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 procedures. 6.Male or non-pregnant, non-lactating females. No wish to become pregnant in the coming 26 weeks.
Exclusion criteria
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 infliximab (intravenous or subcutaneous) 4. Previously unacceptable side effects or intolerance to all immunosuppressants (both thiopurines and methotrexate) 5. Treatment with adalimumab within 15 days and vedolizumab and 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 (Not applicable in Korea) 8. Ongoing participation in another interventional trial 9. Patients with ulcerative colitis or 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 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 HPV 17. History of cancer in the last 5 years with the exception of non-melanoma skin cancer 18. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures 19. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures 20. Patients unable to attend all study visits 21. Patients with a history of non-compliance with clinical study protocols 22. Contraindication for endoscopy 23. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer 24. Pregnancy or lactation 25. Patients whose weight exceeds 80kg at the screening visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients in corticosteroid-free clinical remission (as defined by CDAI<150) ;The proportion of patients in endoscopic response (a drop of at least 50% in SES-CD compared to baseline) | — |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of patients in endoscopic remission at week 26 (defined as the absence of ulcerations larger then 5 mm);Proportion of patients with endoscopic remission at week 26 (as measured by SES-CD=2);Proportion of patients with endoscopic response at week 26 (as measured by at least 50% reduction in the SES-CD as compared to baseline);Proportion of patients in corticosteroid-free clinical remission at week 26 (defined as a CDAI<150) ;The proportion of patients in CSF deep remission at week 26, as defined by corticosteroid-free clinical (CDAI<150) AND endoscopic remission (defined as the absence of ulcerations larger then 5 mm);Proportion of patients in clinical remission at week 2, 4, 8, 14 and 26 (defined as a CDAI<150);Proportion of patients achieving clinical response at week 2, 4, 8, 14 and 26 (defined as a CDAI-70) ;Proportion of patients achieving clinical response at week 26 (defined as a CDAI-100) ;Proportion of patients in symptomatic remission at week 2, 4, 8, 14 and 26 (defined as a PRO-2 [stool frequency and abdominal pain] <8) ;Proportion of patients achieving symptomatic response at week 2, 4, 8, 14 and 26 (defined as a PRO-2 -8);Time to symptomatic remission (defined as a PRO-2 [stool frequency and abdominal pain] <8);Proportion of patients in biochemical remission at week 8, 14 and 26 (CRP=5.0 mg/L and fecal calprotectin<250 mg/kg);Time to biochemical remission (CRP=5.0 mg/L and fecal calprotectin<250 mg/kg);Proportion of patients achieving minimally clinically important difference in quality of life at week 2, 4, 8, 14 and week 26 compared to baseline as assessed by the IBDQ and EQ-5D-5L questionnaire;Proportion of patients developing anti-drug antibodies (ADA) against IFX at week 2, 4, 8, 14 and 26 as measured by a drug-tolerant assay;IFX trough levels at week 2, 4, 8, 14 and 26;HLA haplotyping and genotyping for correlation with efficacy and ADA development(Implemented only in the Dutch patient group);DNA methylation analysis in association w | — |
Countries
Korea, Republic of
Contacts
Public ContactEun Ja Youn
Asan Medical Center
Outcome results
None listed