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).
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.
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.
Ileorectal anastomosis (rectum < 15 cm), or a proctocolectomy.
Short bowel syndrome.
Parallel
Epigenome-Guided Treatment Arm
DeviceParticipants 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.
Investigator-Guided Treatment Arm
Other interventionAssigned to UST or VDZ per conventional SOC and without the use or knowledge of epigenome results.
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 \[SES-CD\])
To explore the optimal threshold of EpiPredict results in predicting treatment response using data from participants assigned to the epigenome-guided treatment selection group
Receiver-operating characteristic curve area analysis will be used Predicted likelihood of success of reaching corticosteroid-free clinical remission and endoscopic response
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
Endoscopic response (≥ 50% decrease from baseline in SES-CD score) Endoscopic remission (SES-CD ≤ 3) Clinical remission (HBI ≤ 4) Corticosteroid-free clinical remission Clinical response (decrease in HBI ≥ 3 points from baseline) Corticosteroid-free deep remission (HBI ≤ 4 and SES-CD ≤ 3)
To evaluate the cost-effectiveness of epigenome-guided treatment selection compared to usual SOC treatment selection
Societal costs as measured by the modified iMTA Medical Cost Questionnaire and modified iMTA Productivity Cost Questionnaire questionnaires Quality of life-years as measured by the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) questionnaire
To assess the safety of a treatment based on epigenome-guided treatment selection compared to usual SOC treatment selection
Adverse events CD-related complications, hospitalisations, and/or surgeries
To explore additional efficacy measures of epigenome-guided treatment selection compared to usual SOC treatment selection at Week 26 in participants with active CD.
Achieving a minimally clinically important difference in patient-reported health-related quality of life (HRQOL) compared to baseline as measured by the EQ-5D-5L Clinical remission (HBI ≤ 4) Clinical response (decrease in HBI ≥ 3 points from baseline) Clinical remission (Crohn's Disease Activity Index \[CDAI\] score of \< 150) over time Time to symptomatic remission (HBI ≤ 4) No drainage on gentle finger compression in participants with draining fistulas Extra-intestinal manifestations Histologic response, as defined in the statistical analysis plan (SAP) Histologic remission, as defined in the SAP Whether the participant achieved 25%, 50%, and 75% reduction from baseline in the Robarts Histopathology Index (RHI) score Serum trough concentrations of biologic drug Biochemical remission CRP ≤ 5.0 mg/L and/or fecal calprotectin \[FC\] \< 250 µg/g) Change in the Symptoms and Impact Questionnaire-CD (SIQ-CD) score
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
Proportion of participants with IUS response (defined as by reduction in bowel wall thickness \[BWT \> 25%\] or \[\> 2.0 mm\] or \[\> 1.0 mm and one colour Doppler signal (CDS) reduction\]) Proportion of participants with transmural remission (defined by BWT ≤ 3 mm and normal/0 CDS) Proportion of participants with transmural remission and endoscopic remission
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Alimentiv Inc.
Lead sponsor
The Leona M. and Harry B. Helmsley Charitable Trust
Collaborator
Horizon Europe
Collaborator
Stichting Amsterdam UMC
Collaborator
