Clinical trial NCT06113913: Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
Official title: Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
Crohn Disease
Ulcerative Colitis
Keywords: remission
infliximab
Lead sponsor: Belgian Inflammatory Bowel Disease Research and Development (BIRD) VZW
Sponsor class: OTHER
Collaborators: name: Celltrion
First posted: 2023-11-02
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: • The proportion of patients that maintain steroid-free clinical and biological remission by week 52 without treatment optimization after switch to SC infliximab (composite endpoint)
timeFrame: week 52
Secondary outcomes:
measure: • The proportion of patients that maintain steroid-free clinical and biological remission by week 52 with treatment optimization
timeFrame: week 52
measure: • The proportion of patients that maintain steroid-free clinical and biological remission by week 52 (with or without treatment optimization)
timeFrame: week 52
measure: • The proportion of patients that maintain steroid-free clinical and biological remission by week 8, by week 24 (without treatment optimization)
timeFrame: week 8 and week 24
measure: • The proportion of patients that maintain steroid-free clinical remission by week 8, by week 24, by week 52 (without treatment optimization)
timeFrame: week 8, week 24 and week 54
measure: • The proportion of patients that maintain steroid-free biological remission by week 8, by week 24, by week 52 (without treatment optimization)
timeFrame: week 8, week 24 and week 52
measure: • The proportion of patients switching back to IV infliximab by week 8, by week 24, by week 52
timeFrame: week 6, week 24 and week 52
measure: • Time to an objectified clinical relapse
timeFrame: over 52 weeks
measure: • Time to treatment optimization
timeFrame: over 52 weeks
measure: • Time to treatment discontinuation
timeFrame: over 52 weeks
measure: • Patients experience and satisfaction score with switching to SC therapy by week 8, week 24 and by week 52.
timeFrame: week 8, week 24 and week 52
measure: • The proportion of eligible patients willing to switch and effectively switching to SC therapy
timeFrame: week 0
measure: • Identification of reasons for willing or not willing to switch to SC therapy
timeFrame: week 0
measure: • Identification of reasons for treatment optimization (clinical disease activity, biological disease activity, endoscopic disease activity, radiological disease activity, and/or other)
timeFrame: over 52 weeks
measure: • Identification of reasons for treatment discontinuation (clinical disease activity, biological disease activity, endoscopic disease activity, radiological disease activity, adverse events, pregnancy, patient's request, and/or other)
timeFrame: over 52 weeks
measure: • The number and type of (serious) adverse events by week 52 or 54
timeFrame: week 52
Other outcomes:
measure: The association of infliximab trough level and antibody level (if available) at screening to the maintenance of clinical and biological remission after switch to SC infliximab.
timeFrame: Between week 0 and week 52
measure: The association of the IV dosing schedule to the maintenance of clinical and biological remission after switch to SC infliximab.
timeFrame: Between week 0 and week 52
measure: The total cost of infliximab therapy
timeFrame: Between week 0 and week 52
measure: The quality-adjusted life years
timeFrame: Between week 0 and week 52
measure: The total cost to quality-adjusted life year ratio
timeFrame: Between week 0 and week 52
Locations:
city: Gent
country: Belgium
facility: AZ Maria Middelares
state: Oost-Vlaanderen
city: Oostende
country: Belgium
facility: AZ Oostende
state: West-Vlaanderen
city: Antwerp
country: Belgium
facility: Universitair ziekenhuis Antwerpen
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Brussel
country: Belgium
facility: Erasme
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Gent
country: Belgium
facility: AZ Sint-Lucas Gent
city: Gent
country: Belgium
facility: Universitair ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitair ziekenhuis Leuven
city: Lier
country: Belgium
facility: Heilig Hart ziekenhuis Lier
city: Liège
country: Belgium
facility: CHU Liège - Sart Tilman
city: Sint-Niklaas
country: Belgium
facility: VITAZ
city: Tongeren
country: Belgium
facility: AZ Vesalius
city: Tournai
country: Belgium
facility: CHwapi
Study officials:
affiliation: Department of Gastroenterology, VITAZ Sint-Niklaas
name: Tom Holvoet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology Heilig Hartziekenhuis Lier
name: Annick Moens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: