Subcutaneous infliximab after a previous intravenous dose optimization (AMARETTO trial)
- Conditions
- Ulcerative colitis (UC), Inflammatory bowel disease type unclassified (IBDU) and Crohn's disease (CD)
- Registration Number
- 2023-508166-15-00
- Lead Sponsor
- Belgian IBD Research and Development
- Brief Summary
To compare clinical and biological outcome between a regimen with subcutaneous infliximab every week and subcutaneous infliximab every other week among patients who were in clinical and biological remission with an optimized intravenous schedule when they switched to subcutaneous 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.
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 275
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 dosing schedule for at least 20 weeks.
Patients receiving an average IV infliximab per eight weeks based on the two most recent IV administrations of more than 8 mg/kg, but not more than 22 mg/kg.
Patients who speak and read fluently Dutch, French or English.
Patients who is able to voluntary give their written informed consent.
Male or female < 18 years
Patients with an ileorectal anastomosis, an ileal pouch-anal anastomosis or an ostomy (transient or permanent)
Patients participating in an interventional clinical trial with an Investigational Medicinal Product (IMP) or device.
Patients previously treated with subcutaneous infliximab.
Patients with active perianal fistulizing disease.
Patients with microscopic colitis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The proportion of patients that maintain steroid-free clinical and biological remission by week 52 without treatment optimization after switch to subcutaneous infliximab. The proportion of patients that maintain steroid-free clinical and biological remission by week 52 without treatment optimization after switch to subcutaneous infliximab.
- Secondary Outcome Measures
Name Time Method The proportion of patients that maintain steroid-free clinical and biological remission by week 52 with treatment optimization. The proportion of patients that maintain steroid-free clinical and biological remission by week 52 with treatment optimization.
The proportion of patients that maintain steroid-free clinical and biological remission by week 52 (with or without treatment optimization). The proportion of patients that maintain steroid-free clinical and biological remission by week 52 (with or without treatment optimization).
The proportion of patients that maintain steroid-free clinical and biological remission by week 8, by week 24 (without treatment optimization). The proportion of patients that maintain steroid-free clinical and biological remission by week 8, by week 24 (without treatment optimization).
The proportion of patients that maintain steroid-free clinical remission by week 8, by week 24, by week 52 (without treatment optimization). The proportion of patients that maintain steroid-free clinical remission by week 8, by week 24, by week 52 (without treatment optimization).
The proportion of patients that maintain steroid-free biological remission by week 8, by week 24, by week 52 (without treatment optimization). The proportion of patients that maintain steroid-free biological remission by week 8, by week 24, by week 52 (without treatment optimization).
The proportion of patients switching back to IV infliximab by week 8, by week 24, by week 52. The proportion of patients switching back to IV infliximab by week 8, by week 24, by week 52.
Time to (objectified) clinical relapse (or treatment optimization or treatment discontinuation). Time to (objectified) clinical relapse (or treatment optimization or treatment discontinuation).
Time to objectified clinical relapse (or treatment optimization or treatment discontinuation). Time to objectified clinical relapse (or treatment optimization or treatment discontinuation).
Time to treatment optimization (or treatment discontinuation). Time to treatment optimization (or treatment discontinuation).
Time to treatment discontinuation. Time to treatment discontinuation.
Time to clinical relapse (patients that undergo treatment optimization or treatment discontinuation without clinical relapse will be regarded as lost to follow-up from that timepoint). Time to clinical relapse (patients that undergo treatment optimization or treatment discontinuation without clinical relapse will be regarded as lost to follow-up from that timepoint).
Time to objective clinical relapse (patients that undergo treatment optimization or treatment discontinuation without objective clinical relapse will be regarded as lost to follow-up from that timepoint). Time to objective clinical relapse (patients that undergo treatment optimization or treatment discontinuation without objective clinical relapse will be regarded as lost to follow-up from that timepoint).
Patients experience and satisfaction with switching to SC therapy by week 8, week 24, by week 52. Patients experience and satisfaction with switching to SC therapy by week 8, week 24, by week 52.
The proportion of eligible patients willing to switch and effectively switching to SC therapy. The proportion of eligible patients willing to switch and effectively switching to SC therapy.
Baseline characteristics linked to willingness of switching and effectively switching to SC therapy. Baseline characteristics linked to willingness of switching and effectively switching to SC therapy.
Reasons for willing or not willing to switch to SC therapy. Reasons for willing or not willing to switch to SC therapy.
Reasons for treatment optimization (clinical disease activity, biological disease activity, endoscopic disease activity, radiological disease activity, and/or other). Reasons for treatment optimization (clinical disease activity, biological disease activity, endoscopic disease activity, radiological disease activity, and/or other).
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). 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).
The number and type of (serious) adverse events by week 52. The number and type of (serious) adverse events by week 52.
Trial Locations
- Locations (18)
Ziekenhuis Aan De Stroom
🇧🇪Antwerp, Belgium
AZ Sint-Lucas & Volkskliniek
🇧🇪Gent, Belgium
Ziekenhuis Oost Limburg
🇧🇪Genk, Belgium
Az Maria Middelares Gent
🇧🇪Gent, Belgium
Heilig-Hartziekenhuis Lier
🇧🇪Lier, Belgium
Onze-Lieve-Vrouwziekenhuis
🇧🇪Aalst, Belgium
Az St-Jan Brugge-Oostende A.V.
🇧🇪Brugge, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
CHU De Liege
🇧🇪Liege, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Scroll for more (8 remaining)Ziekenhuis Aan De Stroom🇧🇪Antwerp, BelgiumClara ThienpontSite contact032852739clara.thienpont@zas.be