Optimal Care With Guselkumab in Crohn's Disease / OPTIM Study A Prospective Open Label Interventional, Multicenter Study

NCT07616687 | Recruiting Phase 4

• 2 other identifiers: GETAID-2025-032025-524573-16-00
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Crohn Disease (CD); Intensification

Keywords

Crohn's disease; Intensification; Guselkumab

Outcome Measures

Primary Outcomes (2)

• - 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)

Secondary Outcomes (10)

• - 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),

  Week 48

• SFCR associated with fecal calprotectin < 250 ug/g at Week 12, Week 24 and Week 48,

  Week 12, Week 24 and Week 48

• Clinical remission at Week 12, Week 24 and Week 48

  Week 12, Week 24 and Week 48

• Biomarker remission at Week 12, Week 24 and Week 48

  Week 12, Week 24 and Week 48,

• Need for GUS dose intensification (Week 12, Week 24 and Week 48)

  Week 12, Week 24 and Week 48

Study Arms (1)

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.

Drug: Guselkumab

Interventions

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.

Guselkumab Dose Optimization Strategy

Eligibility Criteria

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

You may qualify if:

• \- Patients with a diagnosis of CD according to ECCO guidelines,
• years of age or older at the time of informed consent,
• Absence of contraindication to guselkumab,
• Active disease according to PRO2 (abdominal pain \> 1 or stool frequency \> 3), and faecal calprotectin \> 250 ug/g,
• Objective active disease documented within ≤ 2 months by endoscopy or by MRI when not contraindicated, orby IUS),
• Not currently participating in any interventional research.
• Patient naïve or exposed to one or more advanced therapy, in accordance with the approved indication for guselkumab in Crohn's disease.
• Females of childbearing potential must have a negative serum pregnancy test at the baseline Visit.

You may not qualify if:

• \- Patient under legal protection,
• Previous exposure to an anti-IL23
• Combination of advanced therapy with GUS,
• Patient with ostomy,
• Pregnant or breastfeeding woman,
• Patient with perianal CD predominant disease.
• Active clinically significant infection or HIV, Hep B, Hep C, or active tuberculosis

Sponsors & Collaborators

• Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives: lead

Study Sites (1)

Chu Amiens Picardie

Amiens, 80054, France

RECRUITING

Related Publications (7)

• 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.

  PMID: 38437854 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.

  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.

  PMID: 38877997 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.

  PMID: 29935327 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.

  PMID: 34688373 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.

  PMID: 34051983 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Interventions

guselkumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Mathurin Fumery, Investigator

  Hospital of Amiens, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MIRA RAAD

CONTACT

0033 6 85 29 97 64; mraad@getaid.org

Marie Coisnon

CONTACT

0033 6 08 95 94 11; mcoisnon@getaid.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: All participants receive guselkumab treatment with protocol-defined dose optimization based on clinical response after the induction period
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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): * Primary responders, defined as a decrease ≥ 30% in PRO2 and ≥ 25% in FC, will receive GUS 100 mg every 8 weeks as maintenance therapy. * Primary non-responders, defined as the absence of a ≥ 30% decrease in PRO2 or a ≥ 25% decrease in FC at Week 12, will directly receive GUS 200 mg every 4 weeks as maintenance therapy. 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.

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: June 1, 2026
• Study Start: June 18, 2026
• Primary Completion (Estimated): March 15, 2029
• Study Completion (Estimated): March 15, 2029
• Last Updated: June 30, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)