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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-524573-16-00 | EU Trial (CTIS) Number |
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Crohn's disease (CD) is a chronic and destructive inflammatory disease of the gastrointestinal tract characterized by phases of relapse and remission. Tumor necrosis factor (TNF) antagonists, anti-integrins and anti-interleukin (IL) 12/23 are the main therapeutic agents to obtain deep remission and prevent disability. Despite the significant advances these biologics represent in treating inflammatory bowel disease (IBD), many patients experience suboptimal responses, including primary non-response or a loss of effectiveness over time, often leading to treatment discontinuation. For all these medications, a dose-response relationship has been demonstrated and an increase in dose or dosing frequency is recommended. Dose escalation is now an essential therapeutic approach necessary in 30 to 50% of CD patients treated with biologics. This strategy, supported by international guidelines, allows for long-term efficacy to be maintained without compromising safety.
Guselkumab (GUS) is a monoclonal antibody targeting the p19 subunit of IL-23. In a recent phase III trial (GALAXI), GUS demonstrated superiority of both subcutaneous (SC) maintenance doses (200 mg every 4 weeks [q4w] and 100 mg every 8 weeks [q8w]) compared to placebo and ustekinumab. In the GALAXI phase III program, at least 30% of patients did not achieve clinical response after a 12-week intravenous induction, and almost 20% experienced a loss of response by week 44. In these patients, the benefit of an intensified dose of GUS (200 mg q4w) maintenance remains to be determined to guide clinicians in optimizing its use in clinical practice. The investigator aimed to evaluate the one-year effectiveness of GUS in CD in real-world settings and under optimal conditions allowing dose intensification.
Interventionnel, open multicenter study, the objectives are:
Primary Objective To evaluate the one-year effectiveness of GUS in CD in real-world setting.
Secondary Objectives
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Guselkumab Dose Optimization Strategy | Experimental | Participants with active Crohn disease receive guselkumab treatment as part of a treat-to-target strategy. During maintenance therapy, dose optimization may be performed according to clinical response criteria defined in the protocol. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Guselkumab | Drug | Guselkumab is a human monoclonal antibody targeting IL-23. In this study, patients receive guselkumab as part of a treat-to-target strategy. At week 12 (W12), patients are managed according to disease response: those with adequate response continue standard maintenance dosing, while non-responders are escalated to an intensified treatment regimen with adjusted dosing frequency. |
| Measure | Description | Time Frame |
|---|---|---|
| - Steroid free clinical remission (SFCR) associated with fecal calprotectin < 250 ug/g at Week 48 | Steroid-free clinical remission (SFCR), defined as clinical remission measured by the patient reprt outcome, PRO2 : abdominal pain ≤ 1 and stool frequency ≤ 3, without corticosteroid use at the time of assessment, combined with fecal calprotectin < 250 µg/g. | Week 48 +/- 12Weeks for the patients who are intensified between Week 32 and Week 48 |
| - Steroid free clinical remission (SFCR) associated with fecal calprotectin < 250 ug/g at Week 48 | Steroid free clinical remission measured by abdominal pain ≤ 1 and stool frequency ≤ 3 with feacal calprotection < 250 ug/g at Week 48 | Week 48 (+/-12Weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| - Morphological remission at Week 48 assessed using the same tool that was used for the patient's inclusion: endoscopy, MRI or IUS (major secondary endpoint), | Evaluation of the morphological remission at W48 by one of the morphological exams: endoscopy: SES-CD <3 points, MRI: bowel wall thickness ≤3 mm without contrast enhancement, IUS: bowel wall thickness ≤3 mm without color doppler signal | Week 48 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| MIRA RAAD | Contact | 0033 6 85 29 97 64 | mraad@getaid.org | |
| Marie Coisnon | Contact | 0033 6 08 95 94 11 | mcoisnon@getaid.org |
| Name | Affiliation | Role |
|---|---|---|
| Mathurin Fumery, Investigator | Hospital of Amiens, France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chu Amiens Picardie | Recruiting | Amiens | 80054 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38437854 | Background | Dolinger M, Torres J, Vermeire S. Crohn's disease. Lancet. 2024 Mar 23;403(10432):1177-1191. doi: 10.1016/S0140-6736(23)02586-2. Epub 2024 Mar 1. | |
| Background | 7. Panaccione R, Hart A, Steinwurz F et al. S1052 Efficacy and Safety of Subcutaneous Guselkumab Induction Therapy in Patients With Moderately to Severely Active Crohn's Disease: Results Through Week 48 From the Phase 3 GRAVITI Study. Am J Gastroenterology 119(10S):p S740-S741, October 2024 | ||
| Background | 6. Panaccione, R et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn's disease: results of the GALAXI 2 & 3 phase 3 studies. Oral presentation (Abstract #1057b) at Digestive Disease Week (DDW) 2024. May 2024. | ||
| 38877997 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 26, 2026 |
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All eligible patients will receive subcutaneous guselkumab (GUS) 400 mg every 4 weeks during the induction period at Weeks 0, 4, and 8.
At Week 12, treatment response will be assessed based on patient-reported outcomes (PRO2) and fecal calprotectin (FC):
In case of loss of response for the primary responders between Weeks 12 and 48 defined as an increase in FC > 25% with a minimum cutoff of 250 µg/g, or an FC value > 250 µg/g at Week 24, or objective disease activity confirmed by IUS, MRI, treatment will be intensified to GUS 200 mg every 4 weeks.
This response-driven treatment strategy explains the need for additional visits during the maintenance period.
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All participants receive guselkumab treatment with protocol-defined dose optimization based on clinical response after the induction period
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| SFCR associated with fecal calprotectin < 250 ug/g at Week 12, Week 24 and Week 48, | Evaluation of the clinical remission by PRO2: abdominal pain ≤ 1 and stool frequency ≤ 3, without corticoids associates with a biological remission defined by calprotectin < 250 ug/g | Week 12, Week 24 and Week 48 |
| Clinical remission at Week 12, Week 24 and Week 48 | Evaluation of the Clinical remission at the visits by the patient report outcome PRO2: abdominal pain ≤ 1 and stool frequency ≤ 3 | Week 12, Week 24 and Week 48 |
| Biomarker remission at Week 12, Week 24 and Week 48 | Evaluation of the biomarker remission: CRP < 5 g/L and fecal calprotectin <250 ug/g | Week 12, Week 24 and Week 48, |
| Need for GUS dose intensification (Week 12, Week 24 and Week 48) | Evaluation of the need of intensification at the visits if the FC increase (> 25% with a minimal cut-off of 250 ug/g) between W12 and W48 or by a FC > 250 µg/g at W24, or disease activity confirmed by : Endoscopy: SES-CD > 3 points or IUS: bowel wall thickness ≥ 3 mm and/or with color doppler signal, or MRI : bowel wall thickness ≥3 mm and/or with contrast enhancement. | Week 12, Week 24 and Week 48 |
| Serum levels of guselkumab (Week 12, Week 24 and Week 48) | Analysis of the serum level of guselkumab | Week 12, Week 24 and Week 48 |
| Neutralizing antibodies to guselkumab (Week 12, Week 24 and Week 48) | Evaluation of the neutralization antibodies to guselkumab | Week 12, Week 24 and Week 48 |
| Crohn's Disease-related hospitalization during study period (Week 12, Week 24 and Week 48) | Crohn's Disease-related hospitalization during study period | Week 12, Week 24 and Week 48 |
| -Change in the Short Inflammatory Bowel Disease Questionnaire(SIBD-Q) from baseline (Week 12, Week 24 and Week 48) | Analysis of the change in SIBD-Q (quality of life index) during the study Score range: 10 - 70 The higher the score, the better the patient's clinical status (i.e., greater likelihood of remission). | Week 12, Week 24 and Week 48 |
| Guselkumab persistence | Evaluation of the Guselkumab persistence during the study | Week 48 |
| Background |
| Gordon H, Minozzi S, Kopylov U, Verstockt B, Chaparro M, Buskens C, Warusavitarne J, Agrawal M, Allocca M, Atreya R, Battat R, Bettenworth D, Bislenghi G, Brown SR, Burisch J, Casanova MJ, Czuber-Dochan W, de Groof J, El-Hussuna A, Ellul P, Fidalgo C, Fiorino G, Gisbert JP, Sabino JG, Hanzel J, Holubar S, Iacucci M, Iqbal N, Kapizioni C, Karmiris K, Kobayashi T, Kotze PG, Luglio G, Maaser C, Moran G, Noor N, Papamichael K, Peros G, Reenaers C, Sica G, Sigall-Boneh R, Vavricka SR, Yanai H, Myrelid P, Adamina M, Raine T. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2024 Oct 15;18(10):1531-1555. doi: 10.1093/ecco-jcc/jjae091. No abstract available. |
| 29935327 | Background | Peyrin-Biroulet L, Danese S, Argollo M, Pouillon L, Peppas S, Gonzalez-Lorenzo M, Lytras T, Bonovas S. Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2019 Apr;17(5):838-846.e2. doi: 10.1016/j.cgh.2018.06.026. Epub 2018 Jun 20. |
| 34688373 | Background | Singh S, Murad MH, Fumery M, Sedano R, Jairath V, Panaccione R, Sandborn WJ, Ma C. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1002-1014. doi: 10.1016/S2468-1253(21)00312-5. Epub 2021 Oct 22. |
| 34051983 | Background | Feuerstein JD, Ho EY, Shmidt E, Singh H, Falck-Ytter Y, Sultan S, Terdiman JP; American Gastroenterological Association Institute Clinical Guidelines Committee. AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn's Disease. Gastroenterology. 2021 Jun;160(7):2496-2508. doi: 10.1053/j.gastro.2021.04.022. No abstract available. |
| May 6, 2026 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| C000588857 | guselkumab |
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