Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease

Study Sites: Approximately 27 pediatric clinical centers in North America Study Period: Planned enrollment period - 3 years Planned duration of the study: 5 years Primary Study Objective: Identify clinical, radiologic, genomic, immune, microbial and transcriptomic factors associated with complete intestinal healing (CH) in the context of optimized anti-TNF therapy in children with newly diagnosed CD Secondary Study Objective: Identify clinical, radiologic, genomic, immune, microbial and transcriptomic factors associated with endoscopic healing only, transmural healing by MRE only, endoscopic response only, transmural response only, clinical remission, fecal calprotectin normalization, in the context of optimized anti-TNF therapy in children with newly diagnosed CD Study Design: Prospective multicenter open label single arm clinical trial with 2-phase enrollment Sample Size: Phase 1: 900; Phase 2: 550

Phase 1 Inclusion Criteria

• Age ≥ 6 years and < 18 years at enrollment
• Suspected diagnosis of CD
• Stool culture if performed that is negative for routine enteric pathogens (Salmonella, Shigella, Campylobacter, E. coli 0157:H7) and Clostridium difficile toxin in patients presenting with diarrhea. If history of C. difficile then a minimum of 6 weeks duration from treatment start and negative repeat stool for C. difficile toxin.
• Parent/guardian consent and patient assent
• Ability to remain in follow-up for up to 6 months of initial observation followed by a minimum of 52 weeks after possible start of anti-TNF therapy

Phase 1 Exclusion Criteria

• Diagnosis of CD following abdominal resectional surgery/appendectomy at initial presentation
• Investigator judgment that patient has high likelihood (>50%) of needing bowel resection within 3 months of diagnosis (i.e., presentation with perforation, bowel obstruction from stricture)
• Use of any oral CS for non-gastrointestinal indication within the four weeks prior to diagnostic assessment and biosampling (e.g., asthma)
• Use of any investigational drug within the past four weeks prior to diagnostic assessment and sampling
• Pregnancy
• Patients with poorly controlled medical conditions (e.g. diabetes, congestive heart failure)
• Previous treatment with immunomodulators within one year of enrollment or anti-TNF therapy within two years of enrollment for other medical conditions (e.g., juvenile idiopathic arthritis)
• Previous treatment with non-anti TNF biologics or small molecules for non-IBD indications in the past 6 months, with the exception of dupilumab (Dupixent) for asthma, eczema, or eosinophilic esophagitis
• Inability to have MRE because of claustrophobia or other reasons

Phase 2 Inclusion Criteria

• Met all eligibility criteria for Phase 1 and participated in Phase 1
• Diagnosed with macroscopic CD involving the terminal ileum and/or colon by endoscopic evaluation and/or MRE
• MRE imaging within 6 weeks of ileocolonoscopy and no more than 4 weeks after starting initial therapy (TT). A limited 'research protocol' MRE is acceptable in participants who have undergone a clinical CTE during their initial diagnostic evaluation; see Manual of Procedures for details.
• Received at least one of the following as initial therapy upon diagnosis:

• Corticosteroids
• Immunomodulator
• Aminosalicylic acids (5-ASA)
• Defined nutritional therapy
• Anti-TNF (adalimumab or infliximab)
• Commenced adalimumab or infliximab anti-TNF therapy guided by ROADMAB™ CDST as first therapy or within 180 days of diagnosis (TD), with or without concomitant immunomodulator

6 a. Had ileal and rectal biopsies, OR b. Ileal biopsies are not obtained secondary to inflammatory or structural changes at the ileocecal valve or distal ileum that prevent ileal intubation. To be acceptable for Phase 2, the following additional criteria must be met: b1. Gross inflammation or obvious narrowing at the IC valve or distal ileum as documented by the video colonoscopy, AND b2. MRE documentation of TI inflammation with or without narrowing, OR c. Ileal biopsies are not obtained secondary to inflammatory or structural changes due to colonic CD.

• Parent/guardian consent and patient assent 8. Ability to remain in follow-up for a minimum of 52 weeks after start of anti-TNF therapy

Phase 2 Exclusion Criteria

• Diagnosis of CD using video capsule endoscopy only with normal ileocolonoscopy and normal MRE
• Orofacial CD only
• Esophageal, gastric, duodenal, and/or jejunal CD only
• Severe complex fistulizing perianal disease +/- abscess, or perianal disease requiring surgical intervention or likely to require on-going surgical intervention possibly including diversion. The placement of a seton is not exclusionary. Incision and drainage of a perirectal abscess is also not exclusionary.
• Perianal CD only with no evidence of luminal disease
• Internal fistulizing disease at diagnosis
• Initial IBD treatment with non-anti-TNF biologic or small molecule therapy
• Received any anti-TNF agent other than adalimumab or infliximab
• Investigator judgment that patient unlikely to return for clinical, endoscopic or MRE follow-up
• Inability to have MRE because of claustrophobia or other reasons
• Video of baseline endoscopy not available for central reading, unless otherwise approved by the Clinical Coordinating Center (Adequate photo documentation required)
• Underwent bowel resection within 3 months of diagnosis (TD)