Scientific medical research comparing the effectiveness of Infliximab by injection in the abdominal tissiue (subcutaneous) monotherapy and infliximab subcutaneous injection with anti-inflammatory drugs in the treatment of moderate to severe chronic inflammatory bowel disease.

• Register: EUCTR
• Last refreshed on: 3 February 2025
• Main ID: EUCTR2021-000469-33-NL
• Date of registration: 25/03/2021
• Prospective Registration: Yes
• Primary sponsor: Amsterdam UMC location AMC
• Public title: Scientific medical research comparing the effectiveness of Infliximab by injection in the abdominal tissiue (subcutaneous) monotherapy and infliximab subcutaneous injection with anti-inflammatory drugs in the treatment of moderate to severe chronic inflammatory bowel disease.
• Scientific title: A Prospective Multicenter Randomized Controlled, 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. - DIRECT CD
• Date of first enrolment: 12/10/2021
• Target sample size: 158
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000469-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Monotherapy with remsima, and Combination Therapy with remsima and immunosupressive Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Krisztina Gecse
• Affiliation: Amsterdam UMC location AMC

• Name: Krisztina Gecse
• Affiliation: Amsterdam UMC location AMC

Key inclusion & exclusion criteria

Inclusion criteria:
Patients 18 years or older diagnosed with Crohn’s disease

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 or = 4 for isolated ileal disease.

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 IFX at the discretion of the treating physician.

In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.

The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure.

Male or non-pregnant, non-lactating females. No wish to become pregnant in the coming 26 weeks.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 138
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
Patients at imminent need of surgery as judged by the treating clinician

Patients with the short bowel syndrome, an ostomy or a symptomatic non-inflammatory stricture

Patients previously exposed to IFX (intravenous or subcutaneous)

Previously unacceptable side effects or intolerance to all immunosuppressants (both thiopurines and methotrexate)

Treatment with adalimumab within 15 days and vedolizumab and ustekinumab within 30 days

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)

Enteric pathogens (such as Salmonella, Shigella, Yersinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening

Ongoing participation in another interventional trial

Patients with Ulcerative Colitis or IBD-U

Patients with ongoing abdominal or undrained perianal abscess

Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma, which has been removed

Active or latent tuberculosis (screening according to national guidelines)

Cardiac failure in NYHA stage III-IV

History of demyelinating disease

Recent live vaccination (= 4 weeks)

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

History of cancer in the last 5 years with the exception of non-melanoma skin cancer

Male patients with EBV negative serology

A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures

Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures

Patients unable to attend all study visits

Patients with a history of non-compliance with clinical study protocols

Contraindication for endoscopy

Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer

Pregnancy or lactation or wish to become pregnant in the coming 26 weeks



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Biological Phenomena [G16]

Crohns disease

Intervention(s)

Trade Name: Remsima
Product Name: Remsima
Product Code: EMEA/H/C/002576
Pharmaceutical Form: Solution for infusion in pre-filled syringe

Trade Name: Puri Nethol
Product Name: Puri Nethol
Product Code: RVG00859
Pharmaceutical Form: Tablet

Trade Name: Imuran
Product Name: Imuran
Pharmaceutical Form: Tablet

Trade Name: Thiosix
Product Name: Thiosix
Product Code: RVG 114681
Pharmaceutical Form: Tablet

Trade Name: Ebetrex 15 mg = 0,75 ml, oplossing voor injectie in voorgevulde injectiespuit 20 mg/ml
Product Name: Ebetrex
Product Code: RVG 116648
Pharmaceutical Form: Injection

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week14, and week 26

Main Objective: The aim of this study is to investigate the efficacy of subcutaneous IFX in the treatment of moderate to severe Crohn’s disease with and without concomitant immunosuppression, as measured by the proportion of patients in corticosteroid-free clinical remisison (as defined by a CDAI<150) and endoscopic response (as defined by a SES-CD drop of at least 50%) at week 26. We hypothesize that subcutaneous IFX monotherapy is non-inferior to subcutaneous IFX with concomitant immunosuppression in inducing this combined primary endpoint of CSF clinical remission and endoscopic response by week 26.

Primary end point(s): Proportion of patients in corticosteroid-free clinical remission (as defined by CDAI<150) AND endoscopic response (a drop of at least 50% in SES-CD compared to baseline) at week 26

Secondary Objective: The proportion of patients in endoscopic remission at week 26 (defined as the absence of ulcerations larger then 5mm)

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 5mm)

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)

Secondary Outcome(s)

Secondary end point(s): The proportion of patients in endoscopic remission at week 26 (defined as the absence of ulcerations larger then 5mm)

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 5mm)

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/g)

Time to biochemical remission (CRP = 5.0 mg/L and fecal calprotectin < 250 mg/g)

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

DNA methylation analysis in association in objective response to IFX

Thiopurine metabolites at baseline, week 14 and week 26 (for patients randomized for the combination therapy group, only at baseline for those in the monotherapy group and with previous IS use)

Proportion of patients having IFX trough levels of > 5ug/ml at week 26

Proportion of patients achieving histological healing at week 26

Proportion of patients (of those with active perianal disease at baseline) in clinical remission and response of their perianal disease, as defined by the fistula drainage assessment (FDA) at week 26

Proportion of patients with extraintestinal manifestations at week 26 as compared to baseline

Adverse events

Timepoint(s) of evaluation of this end point: 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 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

If the patient has primary non-response at week 14 (as defined by the discretion of the treating physician), the patient will be considered a study failure and will be withdrawn from the study after EOS endoscopy

Secondary ID(s)

NL.76663.018.21

Source(s) of Monetary Support

Celltrion Healthcare Netherlands B.V.

Ethics review

Status: Approved
Approval date: 12/10/2021
Contact: