Purpose of this study
The purpose of this study is to clinically validate the predictive power and use of peripheral blood epigenetic profiles using an in vitro diagnostic medical device software for personalized treatment selection of approved biologics for Crohn’s disease (CD).
Background
Currently, there is no clinically validated biomarker for optimal treatment selection in CD. DNA methylation marks are promising biomarkers in CD and could guide patient-specific therapy for CD with precision medicine.
Inclusion criteria
- Aged 18 years or older at the time of informed consent.
- Documented diagnosis of ileal, ileocolonic, or colonic CD
- Active CD, as defined by HBI > 6 and SES-CD ≥ 6 for colitis/ileocolitis and ≥ 4 for ileitis only.
- Eligible to receive either vedolizumab and/or ustekinumab 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 standard of care
- Nonpregnant and nonlactating.
- 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.
Exclusion criteria
- Prior treatment with vedolizumab or ustekinumab
- Prior treatment with more than 1 advanced therapy 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 or a proctocolectomy, short bowel syndrome, all ostomies, symptomatic strictures, active abscess.
- History or current diagnosis of ulcerative colitis, indeterminate colitis, idiopathic colitis, microscopic colitis, or colonic mucosal dysplasia
Primary outcome measures
To compare the efficacy of epigenome guided treatment selection to investigator-guided treatment selection for inducing clinical remission and endoscopic response at Week 26 in participants with active CD. Primary endpoints are:
- Corticosteroid-free clinical remission (Harvey-Bradshaw Index (HBI) score ≤ 4)
- Endoscopic response (≥ 50% decrease from baseline in the Simplified Endoscopic Score for Crohn’s Disease (SES-CD))
Secondary objectives
- To explore the optimal threshold of EpiPredict results in predicting treatment response using data from participants assigned to the epigenome-guided treatment selection group.
- To compare the efficacy of epigenome- guided treatment selection to treatment selection for improving clinical and endoscopic outcome measures at Week 26 in participants with active CD.
- To assess, in the investigator-guided treatment selection group, the concordance between biologic received and the prediction by the EpiPredict software, stratified by response status at Week 26 for inducing clinical remission and endoscopic response in participants with active CD.
- To evaluate the cost-effectiveness of epigenome guided treatment selection compared to investigator-guided treatment selection
- To assess the safety of a treatment based on epigenome-guided treatment selection compared to usual SOC treatment selection.
Link to website: https://methylomic.eu/
Study locations in Europe
- The Netherlands
- Belgium
- Hungary
- Italy
- Slovenia
- United Kingdom