Comparison of Vedolizumab Treatment to Adalimumab Dose Intensification in Crohn's Disease Patients With Loss of Response or Biomarker Activity to Adalimumab on First Line With Therapeutic Drug Concentration.

NCT ID: NCT06180382

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-31
• Study Completion Date: 2027-01-31

Brief Summary

A substantial fraction of IBD patients with an initial response to infliximab or adalimumab later experience re-emerging active disease despite ongoing anti-Tumour Necrosis Factor (TNF) agents maintenance therapy. The optimal intervention in patients with secondary loss-of-response (LOR) is still poorly defined, as there are still scant data on how best to choose the next intervention from among dose-intensification, switch to another anti-TNF or switch out of the anti-TNF class. Moreover, according to STRIDE 2 recommendations and CALM study, optimize patients based solely on lack of biological remission (CRP, calprotectin) can be discuss. If CALM study has showed that the intervention arm based on regular monitoring fecal calprotectin, CRP and/or CDAI to optimize patients under adalimumab was significantly associated to an increase rate of mucosal healing that the standard of care strategy based on only clinical activity, TDM was not available to guide drug optimization strategy.

Detailed Description

To address these issues, for IFX or ADA therapy, several studies have proposed some algorithms according to which interventions are based on a combined assessment of IFX or ADA drug level and antibodies-to-IFX or ADA (ATI or AAA) levels at the time of therapeutic failure. Thus, IFX or ADA levels, classified as therapeutic or sub-therapeutic, and detectable or undetectable antibodies, are used to assess if LOR is likely due to immunogenicity, to non-immune-mediated pharmacokinetic problems or due to pharmacodynamic issues, and to guide interventions accordingly.

In the last AGA recommendations, the authors suggested that in case of secondary LOR under anti TNF drug with therapeutic levels to switch to another class (such as vedolizumab). However, recent studies showed that optimization of dose regimen of the same anti-TNF in these patients may still be associated with clinical response in 25% of patients. Indeed, in a recent bicentric, retrospective and non-randomized study, the investigators showed that IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class was significantly better than optimizing ADA, in term of time without discontinuation of treatment.

Conditions

Crohn's Disease

Study Design

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

Study Groups

Adalimumab with optimisation

Patients with Crohn's disease will be included. They will have Adalimumab with optimisation as treatment.

Group Type: EXPERIMENTAL

Adalimumab

Intervention Type: DRUG

Administration of adalimumab with optimisation either 80 mg every 14 days by subcutaneous injection, or the same dose of 40 mg every 7 days.

Vedolizumab

Patients with Crohn's disease will be included. They will have Vedolizumab as treatment.

Group Type: EXPERIMENTAL

Vedolizumab

Intervention Type: DRUG

Strategy B: administration of vedolizumab 300mg by infusion at baseline, 14 days, 42 days and 60 days, followed by a dose of 108mg every fortnight by subcutaneous injection.

Interventions

Adalimumab

Administration of adalimumab with optimisation either 80 mg every 14 days by subcutaneous injection, or the same dose of 40 mg every 7 days.

Intervention Type: DRUG

Vedolizumab

Strategy B: administration of vedolizumab 300mg by infusion at baseline, 14 days, 42 days and 60 days, followed by a dose of 108mg every fortnight by subcutaneous injection.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Major patient and having given consent to participate in the study
• Patients with Crohn's disease who have responded primary to Adalimumab princeps or similar bio with loss of response to Adalimumab (40 mg every two weeks) with therapeutically adequate levels of ADA (> 7.5 μg/mL).
• Patient affiliated to or entitled under a social security scheme

Exclusion Criteria

• Pregnant woman
• Patient unable to perform MRI or VCE or ileocolonoscopy or ultrasound less than one month before inclusion
• Previous or current use of vedolizumab or ustekinumab for Crohn's disease or participation in a biological study
• Concomitant use of immunomodulators
• Patients on corticosteroid therapy
• History of cancer
• History of human immunodeficiency virus (HIV), immunodeficiency syndrome, central nervous system (CNS) demyelinating disease (including myelitis), neurological symptoms suggestive of demyelinating disease, chronic recurrent infection, active tuberculosis (received or untreated), severe infections such as sepsis and opportunistic infections
• Patient with ileoanal pouchitis or ileorectal anastomosis
• Patient with short small bowel syndrome as determined by investigator
• Patients receiving total parenteral nutrition (TPN)
• Patients receiving enteral nutrition
• Patient under legal protection or unable to give consent
• Hemorrhagic rectocolitis or indeterminate colitis
• Patients treated with concomitant immunosuppressive agents
• Patient treated with an optimized dose of adalimumab
• Primary non-responder to Adalimumab
• Patient previously treated with infliximab or ustekinumab before adalimumab
• Severe relapse defined by CDAI > 330
• Patient with anoperineal Crohn's disease
• Crohn's disease patient with transient or permanent stoma.

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

Sponsors

Takeda France

INDUSTRY

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mathilde BARRAU, MD

Role: PRINCIPAL_INVESTIGATOR

CHU de Saint-Etienne

Locations

APHP - Hôpital Bicêtre

Le Kremlin-Bicêtre, Paris, France

Site Status: RECRUITING

CHU Amiens

Amiens, , France

Site Status: RECRUITING

CHRU Lille

Lille, , France

Site Status: RECRUITING

Chu Limoges

Limoges, , France

Site Status: RECRUITING

APHM

Marseille, , France

Site Status: RECRUITING

CHU Montpellier

Montpellier, , France

Site Status: RECRUITING

Hôpital de l'Archet II

Nice, , France

Site Status: RECRUITING

Assistance Publique - Hôpitaux de Paris

Paris, , France

Site Status: RECRUITING

CHU Bordeaux

Pessac, , France

Site Status: RECRUITING

Ch Lyon Sud

Pierre-Bénite, , France

Site Status: RECRUITING

CHU Rennes

Rennes, , France

Site Status: RECRUITING

CHU de Saint-Etienne

Saint-Etienne, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Mathilde BARRAU, MD

Role: CONTACT

mathilde.barrau@chu-st-etienne.fr

(0)477829626 ext. +33

Florence RANCON, project manager

Role: CONTACT

florence.rancon@chu-st-etienne.fr

(0)477829458 ext. +33

Facility Contacts

Aurélien AMIOT, PhD

Role: primary

Mathurin FUMERY, PhD

Role: primary

Maria Nachury, MD

Role: primary

Sophie GEYL, MD

Role: primary

Mélanie SERRERO, MD

Role: primary

Romain Altwegg, PhD

Role: primary

Xavier Hebuterne, PhD

Role: primary

Mathieu UZZAN, MD

Role: primary

David LAHARIE, PhD

Role: primary

Stéphane NANCEY, PhD

Role: primary

Guillaume BOUGUEN, PhD

Role: primary

Mathilde BARRAU, MD

Role: primary

mathilde.barrau@chu-st-etienne.fr

(0)477829626 ext. +33

Other Identifiers

2023-508154-25-00

Identifier Type: OTHER

Identifier Source: secondary_id

23CH214

Identifier Type: -

Identifier Source: org_study_id