Subcutaneous Infliximab After A Previous Intravenous Dose Optimization

NCT ID: NCT06113913

Last Updated: 2024-07-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-09
• Study Completion Date: 2026-11-30

Brief Summary

The goal of this clinical trial is to learn about the treatment with subcutaneous infliximab in patients with inflammatory bowel disease (IBD) that were previously treated with an optimized dose of intravenous infliximab.

The main question it aims to answer is:

• Is switching to a weekly dose of subcutaneous infliximab (120 mg) associated with a better outcome compared to the standard fortnightly administration of 120 mg subcutaneous infliximab in patients who received an optimized intravenous dosing schedule?

Participants will switch from intravenous infliximab to subcutaneous infliximab and will be randomized to the intervention arm (Subcutaneous infliximab weekly) or the interventional comparison arm (subcutaneous infliximab bi-weekly). Participants will follow daily clinical practice in the monitoring for clinical and biological remission.

The participants that are willing to switch to subcutaneous infliximab will be compared to a group of participants not willing to switch. These participants will continue to be treated with their optimized intravenous dose of infliximab.

Detailed Description

Inflammatory bowel diseases (IBD) are a group of immune mediated disorders primarily targeting the gastro-intestinal tract and consist of two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC) that share similarities in both clinical presentation, pathophysiology and treatment. A small proportion of IBD patients cannot be correctly characterized in one of those categories and is referred to as IBD type unclassified (IBDU), which is often classified under UC for clinical research purposes. TNF inhibitors are one of the most frequently prescribed biological therapies and remain an important part of the therapeutic arsenal with international guidelines recommending their use in moderate-to-severe CD and UC when conventional treatments have failed.

Infliximab, a chimer monoclonal antibody against tumor necrosis factor (TNF), was the first anti-TNF agent to be approved for treating IBD as early as 1999. After losing its product patent in 2013, several biosimilars of infliximab have been commercialized including CT-P13. Originally only available in an intravenous (IV) formulation, a subcutaneous (SC) formulation of CT-P13 has been registered for treating moderate-to-severe CD and UC as well. However, many questions on the use of these subcutaneous formulations of infliximab in daily clinical practice remain unanswered, especially in patients who previously required IV dose optimization of infliximab.

The primary objective of the AMARETTO trial is to compare clinical and biological outcome between a regimen with SC infliximab every week and SC infliximab every other week among patients who were in clinical and biological remission with an optimized IV schedule when they switched to SC infliximab.

The secondary objectives of this study are:

• To compare treatment optimization and discontinuation between a regimen with SC inflixmab every week and SC infliximab every other week among patients who were in clinical and biological remission with an optimized IV schedule when they switched to infliximab SC.
• To evaluate the willingness and the experience of patients switching to SC infliximab.
• To compare clinical and biological outcome, as well as treatment optimization and discontinuation between a regimen with SC infliximab (every week or every other week) and IV infliximab among patients who were in clinical and biological remission with an optimized IV schedule.

This study is a national, multicenter, randomized, open-label, prospective, pragmatic trial in Belgium. The trial design is as follows:

• All subjects will undergo screening procedures. The screening visit of eligible patients will include the review of inclusion and exclusion criteria, and the informed consent form procedure. After screening, if the patient fulfils all inclusion and none of the exclusion criteria, and is willing to participate, the gastroenterologist will record the characteristics of patients and of the disease, medical and surgical history, current and past IBD treatments physical examination, the PRO-2 score about the last 3 days before the visit, blood analysis, stool analysis and patients will be asked to fill in a questionnaire about health-related quality of life.
• Afterwards the patients will visit the gastroenterologist 4 times in one year (week 0, week 8, week 24 and week 52, however the specific weeks can vary depending on the IV dosing schedule). During these visits a physical examination will be done, the PRO-2 score based on the 3 previous days before the visit will be calculated, a blood analysis and stool analysis will be done, the concomittant medication will be collected and patients will be asked to answer the questionnaire about the health related quality of life.

NOTE: patients that switch to subcutaneous infliximab will be asked to collect all at home administrations in a diary and to additionnaly answer a questionnaire about the satisfaction of switching to subcutaneous infliximab.

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional (SC infliximab, weekly)

Participants will switch from an optimized dose of intravenous infliximab to an optimized dose of subcutaneous infliximab. This means the participants will inject 120 mg subcutaneous infliximab every week.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

Weekly administration of subcutaneous infliximab.

Interventional comparator (SC infliximab, bi-weekly)

Participants will switch from an optimized dose of intravenous infliximab to subcutaneous infliximab. This means the participants will inject 120 mg subcutaneous infliximab every other week.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

Bi-weekly administration of subcutaneous infliximab.

Intravenous comparator (IV infliximab, optimized dosing schedule)

Participants not willing to switch will continue treatment with intravenous infliximab at the same dosing schedule as before.

Group Type: ACTIVE_COMPARATOR

Infliximab

Intervention Type: DRUG

Optimized dosing schedule of intravenous infliximab.

Interventions

Infliximab

Weekly administration of subcutaneous infliximab.

Intervention Type: DRUG

Infliximab

Bi-weekly administration of subcutaneous infliximab.

Intervention Type: DRUG

Infliximab

Optimized dosing schedule of intravenous infliximab.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any Screening procedures.
• Patients with a previously documented CD, UC, IBDU diagnosis confirmed by clinical, endoscopic, histological, and/or radiological criteria
• Males and females ≥18 years old.
• Patients must be in steroid-free clinical remission at Screening defined as a rectal bleeding score of 0 and a stool frequency score of ≤1 for patients with UC / IBDU, or an average daily abdominal pain score ≤1 and a liquid stool frequency score ≤2.8 for patients with CD (based on the 3 days before the screening visit, excluding the day of or the day before an eventual endoscopy with bowel preparation) and this without the need for any type of steroids in the previous eight weeks.
• Patients must be in biological remission at screening defined as a CRP <10 mg/L and a fecal calprotectin <250 µg/g.
• Patients receiving IV infliximab for at least 26 consecutive weeks.
• Patients receiving a stable IV infliximab dosing schedule for at least 20 weeks.
• Patients receiving an average IV infliximab dose per 8 weeks based on the two most recent IV administration of more than 8 mg/kg, but not more than 22 mg/kg
• Patients who speak and read fluently Dutch, French or English.

Exclusion Criteria

• Male or female ≤ 18 years
• Patients with an ileorectal anastomosis, an ileal pouch-anal anastomosis or an ostomy
• Patients participating in an interventional clinical trial with an Investigational Medicinal Product (IMP) or device
• Patients previously treated with SC infliximab
• Patients with active perianal fistulizing disease
• Patients with microscopic colitis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celltrion

INDUSTRY

Sponsor Role: collaborator

Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tom Holvoet, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology, VITAZ Sint-Niklaas

Annick Moens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology Heilig Hartziekenhuis Lier

Locations

AZ Maria Middelares

Ghent, Oost-Vlaanderen, Belgium

Site Status: RECRUITING

AZ Oostende

Ostend, West-Vlaanderen, Belgium

Site Status: RECRUITING

Universitair ziekenhuis Antwerpen

Antwerp, , Belgium

Site Status: RECRUITING

Imeldaziekenhuis

Bonheiden, , Belgium

Site Status: RECRUITING

AZ Sint-Jan Brugge

Bruges, , Belgium

Site Status: NOT_YET_RECRUITING

Erasme

Brussels, , Belgium

Site Status: RECRUITING

Ziekenhuis Oost-Limburg

Genk, , Belgium

Site Status: RECRUITING

AZ Sint-Lucas Gent

Ghent, , Belgium

Site Status: RECRUITING

Universitair ziekenhuis Gent

Ghent, , Belgium

Site Status: RECRUITING

Universitair ziekenhuis Leuven

Leuven, , Belgium

Site Status: RECRUITING

Heilig Hart ziekenhuis Lier

Lier, , Belgium

Site Status: RECRUITING

CHU Liège - Sart Tilman

Liège, , Belgium

Site Status: RECRUITING

VITAZ

Sint-Niklaas, , Belgium

Site Status: RECRUITING

AZ Vesalius

Tongeren, , Belgium

Site Status: RECRUITING

CHwapi

Tournai, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Ingrid Arijs, Phd

Role: CONTACT

ingrid.arijs@birdgroup.be

+32499317005

Jolien De Rechter

Role: CONTACT

jolien.de.rechter@birdgroup.be

+32498748400

Facility Contacts

Nina Van Heddegem

Role: primary

Louise Vandenbroucke

Role: primary

Aranzazu Amezaga

Role: primary

Peter Bossuyt

Role: primary

Barbara Willandt

Role: primary

Anneline Cremer

Role: primary

Clara Caenepeel

Role: primary

Sophie Claeys

Role: primary

Triana Lobaton

Role: primary

Marc Ferrante

Role: primary

Annick Moens

Role: primary

Catherine Reenaers

Role: primary

Tom Holvoet

Role: primary

Annelies Posen

Role: primary

Maxence Lefebvre

Role: primary

Related Links

http://www.birdgroup.be/en

BIRD website

Other Identifiers

BIRD2023001

Identifier Type: -

Identifier Source: org_study_id