A Prospective Randomised Study of Treatment Selection Based on Epigenetic Markers Versus Standard of Care Treatment Selection in Adults With CROHN's Disease

NCT07363044 | Recruiting DMC

• 1 other identifier: RCT-01727
• Study Type: interventional
• Target: 378
• Locations: 4 countries
• Sites: 30

Brief Summary

This is a multicentre, prospective, randomised, controlled, open-label study to assess the efficacy, safety, and cost-effectiveness of epigenome-guided treatment selection compared to usual standard-of-care (SOC) treatment selection in patients initiating biologic therapy for the treatment of their active Crohn's Disease (CD).

Conditions

Crohn Disease (CD)

Outcome Measures

Primary Outcomes (1)

• To compare the efficacy of epigenome-guided treatment selection to usual SOC treatment selection for inducing clinical remission and endoscopic response at Week 26 in participants with active CD.

  Corticosteroid-free clinical remission (Harvey-Bradshaw Index \[HBI\] score ≤ 4) and endoscopic response (≥ 50% decrease from baseline in the Simple Endoscopic Score for Crohn's Disease \[SES-CD\])

  Baseline to Week 26

Secondary Outcomes (3)

• To explore the optimal threshold of EpiPredict results in predicting treatment response using data from participants assigned to the epigenome-guided treatment selection group

  Baseline to Week 26

• To compare the efficacy of epigenome-guided treatment selection to usual SOC treatment selection for improving clinical and endoscopic outcome measures at Week 26 in participants with active CD

  Baseline to Week 26

• To evaluate the cost-effectiveness of epigenome-guided treatment selection compared to usual SOC treatment selection

  Baseline to 24 Months

Other Outcomes (3)

• To assess the safety of a treatment based on epigenome-guided treatment selection compared to usual SOC treatment selection

  Baseline to Week 26

• To explore additional efficacy measures of epigenome-guided treatment selection compared to usual SOC treatment selection at Week 26 in participants with active CD.

  Baseline to Week 26

• In a subset (~30%) of participants, to evaluate response by intestinal ultrasound (IUS) in participants assigned to epigenome-guided treatment selection compared to usual SOC treatment selection

  Baseline to Week 26

Study Arms (2)

Investigator-Guided Treatment Arm

OTHER

Other: Investigator-Guided Treatment Arm

Epigenome-Guided Treatment Arm

EXPERIMENTAL

Device: Epigenome-Guided Treatment Arm

Interventions

Epigenome-Guided Treatment Arm DEVICE

Participants will receive UST or VDZ biologic therapy as indicated by an epigenome read-out of peripheral blood using a hybrid capture-based methylation assay. The assay and EpiPredict software will indicate the probability of response to VDZ and UST. The biologic with the predicted highest likelihood of success will be communicated to the investigator and the biologic initiated using standard dosing regimens.

Epigenome-Guided Treatment Arm

Investigator-Guided Treatment Arm OTHER

Assigned to UST or VDZ per conventional SOC and without the use or knowledge of epigenome results.

Investigator-Guided Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Participants must meet all of the following criteria for enrolment into the study:
• Aged 18 years or older at the time of informed consent.
• Documented diagnosis of ileal, ileocolonic, or colonic CD (may be confirmed at baseline study endoscopy).
• Active CD, as defined by HBI \> 6 and SES-CD ≥ 6 for colitis/ileocolitis and ≥ 4 for ileitis only.
• Eligible to receive either VDZ and/or UST therapy for the treatment of CD per the approved drug label requirements and in the opinion of the treating physician.
• Must meet all eligibility criteria for biologic therapy initiation as per local SOC, including absence of chronic/opportunistic infections as demonstrated by local protocols for human immunodeficiency virus, tuberculosis, active cytomegalovirus, hepatitis B and C, and Clostridioides difficile infection. Local vaccination protocols apply as per SOC.
• Nonpregnant and nonlactating. Participants of childbearing potential must agree to follow local SOC guidelines for use of biologics in pregnancy/lactation, including appropriate contraception, during the study; must agree to avoid becoming pregnant from the time of informed consent up until Week 26.
• If receiving nonbiologic therapies for inflammatory bowel disease, including thiopurines and methotrexate, must have initiated at least 3 months prior to screening and must be on a stable dose for at least 2 weeks prior to screening.
• If receiving oral corticosteroids, the participant is eligible if they meet all the following criteria:
• The dose is up to a maximum of prednisone ≤ 40 mg/day or budesonide ≤ 9 mg/day or equivalent.
• The dose has been stable for ≥ 2 weeks prior to screening.
• The participant is willing to initiate a corticosteroid taper within 2 weeks after initiating biologic treatment.
• In the opinion of the investigator, the participant is able to understand and comply with protocol requirements including treatment as assigned per the protocol.
• Able to participate fully in all aspects of this clinical study. Full comprehension of consent language and informed consent must be obtained from the participant, or the participant's legally acceptable representative, and documented

You may not qualify if:

• Participants who meet any of the following criteria are to be excluded from the study:
• Prior treatment with VDZ or UST.
• Prior treatment with more than 1 advanced therapy (eg, any biologic \[ie, anti- tumour necrosis factor (TNF), anti-interleukin, anti-integrin\]) or advanced oral small molecule \[ie, Janus kinase inhibitor\]) for CD.
• CD-related complications that in the opinion of the investigator would interfere with participation in the study, including but not limited to:
• Ileorectal anastomosis (rectum \< 15 cm), or a proctocolectomy.
• Short bowel syndrome.
• All ostomies.
• Symptomatic strictures in the bowel or symptomatic strictures in the ileum or ileocecal valve that have a stenosis.
• Suspected or diagnosed active intra-abdominal or perianal abscess that have not been appropriately treated.
• History or current diagnosis of ulcerative colitis (unless this diagnosis was made erroneously), indeterminate colitis, idiopathic colitis (ie, colitis not consistent with CD), microscopic colitis, or colonic mucosal dysplasia (excluding dysplasia in resected adenomas).
• Increased risk of infectious complications (eg, recent pyogenic infection, any congenital or acquired immunodeficiency, or past organ, bone marrow, or stem cell transplantation).
• Any topical rectal therapy for treatment of CD within 2 weeks prior to the screening endoscopy.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) as chronic treatment, except for cyclooxygenase-2logic selective NSAIDS (celecoxib).
• Faecal microbiota transplant (includes human microbiota-based therapeutics) within 4 weeks prior to randomisation.
• Any major surgery (in the investigator's opinion) performed within 8 weeks prior to randomisation or planned during the study.

Sponsors & Collaborators

• Horizon Europe: collaborator
• Stichting Amsterdam UMC: collaborator
• Alimentiv Inc.: lead
• The Leona M. and Harry B. Helmsley Charitable Trust: collaborator

Study Sites (30)

Imeldahospital

Bonheiden, Belgium

RECRUITING

AZ Klina

Brasschaat, Belgium

RECRUITING

H.U.B. - Hôpital Erasme

Brussels, Belgium

RECRUITING

Universitair Ziekenhuis Antwerpen (UZA)

Edegem, Belgium

RECRUITING

AZ Maria Middelares

Ghent, Belgium

RECRUITING

AZ Sint Lucas

Ghent, Belgium

RECRUITING

UZ Gent

Ghent, Belgium

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

Centre Hospitalier Universitaire (CHU) de Liege

Liège, Belgium

RECRUITING

Groupe sante CHC/Clique du MontLegia

Liège, Belgium

RECRUITING

AZ Oostende

Ostend, Belgium

RECRUITING

AZ Delta VZW

Roeselare, Belgium

RECRUITING

CHU UCL Namur asbl Site Godinne

Yvoir, Belgium

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Italy

RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

OLVG Oost

Amsterdam, Netherlands

RECRUITING

Maastricht UMC

Maastricht, Netherlands

RECRUITING

Radboudumc

Nijmegen, Netherlands

RECRUITING

Elisabeth-TweeSteden Ziekenhuis (ETZ)

Tilburg, Netherlands

RECRUITING

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

RECRUITING

Northern Care Alliance - Fairfield General Hospital

Bury, United Kingdom

RECRUITING

Cambridge University Hospitals NHS Trust

Cambridge, United Kingdom

RECRUITING

Hull University Teaching Hospital NHS Trust

Cottingham, United Kingdom

RECRUITING

The Dudley Group NHS Foundation Trust

Dudley, United Kingdom

RECRUITING

Cardiff & Vale UHB

Llandough, United Kingdom

RECRUITING

Guy's and St. Thomas' NHS Foundation Trust

London, United Kingdom

RECRUITING

King's College Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

RECRUITING

Hampshire Hospital NHS Foundation Trust

Winchester, United Kingdom

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Susan Archer

CONTACT

susan.archer@alimentiv.com

Lauren Schleicher

CONTACT

lauren.schleicher@alimentiv.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2026
• First Posted: January 23, 2026
• Study Start: February 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

GB (10); IT (1); BE (13); NL (6)