InDuctIon TREatment with SubCuTaneous Infliximab for Crohn's Disease

NCT06059989 | Recruiting Phase 3

• 1 other identifier: NL76663.018.21
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Inflammatory Disease; Disease Crohn; Bowel Disease

Keywords

Crohn's disease; Biological; Subcutaneous

Outcome Measures

Primary Outcomes (1)

• Crohn's disease activity index <150 (-10 to 480) AND endoscopic response , where the higher score means worse outcome .

  The proportion of patients in corticosteroid-free clinical remission.

  at week 0 and 26

Secondary Outcomes (15)

• Endoscopic remission

  week 0 and 26

• Simple Endoscopic score for Crohn's disease ≤2 ( 0-60) where a higher score means worse outcome

  week 0 and 26

• Crohn's disease activity index <150 (-10 to 480) where a higher score is a worse outcome

  week 0, 2, 4, 8, 14 and 26

• Crohn's disease activity index improved with 70 points (-10 to 480) where a higher score is a worse outcome.

  week 0, 2, 4, 8, 14 and 26

• Crohn's disease activity index improved by100 points( -10 to 480) where a higher score is a worse outcome

  at week 26

Study Arms (2)

Monotherapy

EXPERIMENTAL

Group 1: Monotherapy group Patients randomized to IFX monotherapy start with subcutaneous IFX 240mg at week 0 and 2 and then from week 4, 120mg s.c.EOW.

Drug: Infliximab subcutaneous

Combination therapy

EXPERIMENTAL

Group 2: Combination therapy group Patients randomized to IFX combination therapy start with subcutaneous IFX 240mg at week 0 and 2 and then from week 4, 120mg s.c. EOW. Patients randomized to IFX combination therapy also receive Immunosuppressives EOW.

Drug: Infliximab subcutaneous; Drug: Immunosuppressive Agents

Interventions

Infliximab subcutaneous DRUG

Mono and combination therapy group

Also known as: Remsima 120mg solution s.c.

Combination therapy; Monotherapy

Immunosuppressive Agents DRUG

Combination group only

Also known as: 6-mercaptopurine 1-1.5 mg/kg oral, or, if already on oral azathioprine or thioguanine continuous dosing 2-2.5mg/kg, or 20mg once daily respectively, In case of adverse events or investigator's individual consideration, instead of thiopurine, methotrexate 15 mg/week s.c. (or oral) in combination with oral folic acid 5 mg/week

Combination therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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.
• 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.

You may not qualify if:

• 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 or vedolizumab or 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 Inflammatory bowel disease unclassified (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). Except when the latter has been treated appropriately according to national guidelines.
• Cardiac failure in the New York heart Association (NYHA) stage III-IV
• History of demyelinating disease
• Recent live vaccination (≤ 4 weeks)

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Celltrion: collaborator

Study Sites (1)

Amsterdam UMC AMC

Amsterdam, North Holland, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Crohn Disease; Intestinal Diseases

Interventions

CT-P13; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines

Study Officials

• Dr. G D'Haens, Phd MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  STUDY DIRECTOR

Central Study Contacts

Dr. K. Gecse, MD

CONTACT

+31-20-566-4401; k.b.gecse@amsterdamumc.nl

E Clasquin, MSc

CONTACT

e.clasquin@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Docter IBD specialist

Model Details: 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.

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: September 29, 2023
• Study Start: November 25, 2021
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 10, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)