An Interventional Study to Evaluate Treating to a Target of Transmural Healing in Patients With Moderately to Severely Active Crohn's Disease
Transmural healing (TMH) is recognized as a potentially important measure of Crohn's disease (CD) activity but not a formal target. Observational studies suggest that TMH may be associated with better long-term outcomes. The study will evaluate TMH using noninvasive intestinal ultrasound (IUS), a patient-friendly technique that can be performed routinely in clinical practice. The aim of the study is to determine if treating to a target of corticosteroid-free (CS-free) IUS outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving CS-free endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD). Qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups. Group 1: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH. Group 2: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.
⁃ Participants must meet all of the following criteria for enrolment into the study:
• Adults aged 18 to 80 years, inclusive, at the time of consent;
• Moderately-to-severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease);
• CRP of ≥5 mg/L and/or FCal ≥250 μg/g at Screening;
• BWT on IUS of \>4.0 mm in the ileum or any colonic segment (excluding the rectum);
• Biologic-naïve or have previous exposure to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic;
• Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;
• Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study.
• Females unable to bear children must have documentation of such in the source records;
• Able to participate fully in all aspects of this clinical trial;
• Written informed consent must be obtained and documented.