Clinical trial NCT04131504: Precision Crohn's Disease Management Utilizing Predictive Protein Panels (ENvISION)
Official title: A Multi-Center, Prospective Study to Discover a Companion Diagnostic for Biologics Targeting TNF
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn's Disease
IBD
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
First posted: 2019-10-18
Enrollment: 239
Sex: ALL
Minimum age (years): 1
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Potential IBD participants will be recruited through the Division of Gastroenterology at each participating site.

Healthy volunteers will be recruited from through direct advertising methods approved by the IRB and formal local databases intended for recruitment.

Brief summary: Crohn's disease and ulcerative colitis affect about 1.6 to 3 million people in the United States with many of those being young children and adolescents. Physicians need better ways to inform decisions on therapy selection and recognize ongoing intestinal injury while on treatment.

The main reason for this research study is to see if a blood test or stool test, which measures specific proteins, taken just before starting a new treatment for Crohn's disease can predict a patient's ability to achieve complete intestinal healing. The investigators also want to see if the intensity of gut inflammation can be detected by measuring a separate set of proteins in the blood.

Detailed description: Despite the heterogeneity of CD phenotypes and a potentially aggressive course of inadequately treated CD, treatment selection for newly diagnosed patients is currently based on clinical factors which do not define CD sub-types. Now, with additional biologic therapies for CD, there is a critical need for individual biochemical analysis both pre-treatment, and following induction to assess the probability of durable remission. These data will inform decisions on continued dosing of the current biologic, or whether addition of combination therapy or switching to a therapy with an alternative mechanism of action will be more beneficial.

The Food \& Drug Administration (FDA) defines a companion diagnostic as a device that can identify patients most likely to benefit from a therapy or a device to monitor response with the purpose to adjust the treatment to achieve improved effectiveness.Our global aim is to develop a companion diagnostic (peripheral blood panel) that accurately predicts the probability of deep remission (clinical remission with MH) to anti-TNF and a protein (blood) biomarker panel that reproducibly distinguishes endoscopic MH from active (ulcerated) intestinal inflammation in patients with CD.

The long-term strategy is to utilize the "low-risk" anti-TNF specific module (protein panel) to personalize CD therapy. With the addition of new biologics for CD, patients with a low-risk inflammatory profile would not only be expected to achieve MH but also predicted to respond to treatment escalation strategies while avoiding or stopping the drug (if drug exposure is optimized) sooner in patients in which the protein profile predicts a low probability of deep remission with anti-TNF. As additional therapies are approved for pediatric CD, the priority would be to avoid anti-TNF in patients with a "high-risk" protein profile and specifically select therapies that target the patient's individual inflammatory signature. Additionally, the investigators expect the protein profile of patients failing to achieve deep remission to provide further insight into molecular mechanisms contributing to the continued inflammation and thereby directing the next therapeutic option.

Eligibility criteria: Phase I - Cross-sectional Study (CD and Suspected IBD)

Inclusion Criteria:

1. Age criteria: \> 1 year to \< 22 years of age
2. Diagnosis of Crohn's disease, anti-TNF naïve, and colonoscopy scheduled OR
3. Clinical suspicion for IBD (treatment naïve) and colonoscopy scheduled
4. Permission of parent/guardian and assent or consent of research participant

Exclusion Criteria:

1. Any prior treatment with an anti-TNF, such as infliximab, adalimumab, certolizumab or golimumab
2. Known diagnosis of ulcerative colitis (UC) or inflammatory bowel disease-unspecified (IBD-U)
3. Active or prior evidence of internal (abdominal/pelvic) penetrating fistula(e)
4. Active intra-abdominal abscess or perianal abscess
5. Active Clostridium difficile infection or other known enteric infection in last 2 weeks
6. Current ileostomy or colostomy, extensive small bowel resection, ileoanal pouch or short bowel syndrome
7. History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
8. Any condition that in the opinion of the PI will prevent the research participant from taking part in this study

Phase I - Cross-sectional Study (healthy volunteers)

Inclusion Criteria:

1. Age criteria: \> 1 year to \< 22 years of age
2. Any CCHMC patient
3. Permission of parent/guardian and assent or consent of research participant

Exclusion Criteria:

1. Known diagnosis of one or more of the following: irritable bowel syndrome, gastroesophageal reflux, constipation, BMI\>95% for age, small intestinal bacterial overgrowth (SIBO) or history of intestinal polyps
2. Received any antibiotic in the last 30 days or known viral or bacterial illness in the last 30 days
3. Any NSAID use in the last 14 days
4. History of an autoimmune disease (including diabetes, autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
5. Any condition that in the opinion of the PI will prevent the research participant from taking part in this study

Phase II - Longitudinal Study of Participants with CD

Inclusion Criteria:

1. Age criteria: \> 1 year to \< 22 years of age
2. Diagnosis of Crohn's disease with:

   1. Luminal inflammation (ulcerations in ileum and/or colon visible by ileocolonoscopy) and
   2. Endoscopic evidence of active Crohn's disease (up to 90 days prior to starting anti-TNF) OR if no colonoscopy within 90 days then fecal calprotectin ≥250 µg/g or fecal lactoferrin \>10 µg/g (\<90 days from starting anti-TNF)
3. Anti-TNF naïve
4. Starting infliximab or adalimumab (or either biosimilar)
5. Permission of parent/guardian and assent or consent of research participant

Exclusion Criteria:

1. Crohn's disease limited to esophagus, stomach, duodenum or jejunum
2. Prior treatment with infliximab, adalimumab, certolizumab or golimumab
3. Known diagnosis of Ulcerative colitis (UC) or inflammatory bowel disease-unspecified (IBD-U)
4. Active or prior evidence of internal (abdominal/pelvic) penetrating fistula(e)
5. Active intra-abdominal abscess or perianal abscess
6. Active Clostridium difficile infection or other known enteric infection in last 2 weeks
7. Current ileostomy or colostomy, extensive small bowel resection, ileoanal pouch or short bowel syndrome
8. History of autoimmune disease (including autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, psoriasis or juvenile idiopathic arthritis)
9. Contraindications to MRI scanning, such as metal implants/non-compatible medical devices or medical conditions
10. Any condition that in the opinion of the PI will prevent the research participant from taking part in this study

Primary outcomes:
measure: Sustained Deep Remission
timeFrame: 1 year
Secondary outcomes:
measure: End of Induction Outcomes: Clinical Response
timeFrame: Week 16
measure: End of Induction Outcomes: Clinical Remission
timeFrame: Week 16
measure: End of Induction Outcomes: Steroid Free Clinical Remission
timeFrame: Week 16
measure: End of Induction Outcomes: Fecal Biochemical Response
timeFrame: Week 16
measure: End of Induction Outcomes: Fecal Biochemical Remission
timeFrame: Week 16
measure: End of Induction Outcomes: Blood CRP Biochemical Remission
timeFrame: Week 16
measure: End of Induction Outcomes: Blood CD64 Biochemical Remission
timeFrame: Week 16
measure: Week 52 Outcomes: Endoscopic Response
timeFrame: 1 year
measure: Week 52 Outcomes: Endoscopic Remission
timeFrame: 1 year
measure: Week 52 Outcomes: Minimal Endoscopic Activity
timeFrame: 1 year
measure: Week 52 Outcomes: Complete Intestinal Healing
timeFrame: 1 year
measure: Week 52 Outcomes: Sustained, Steroid-free Clinical Remission
timeFrame: 1 year
measure: Week 52 Outcomes: Clinical Remission
timeFrame: 1 year
measure: Week 52 Outcomes: Clinical Remission and Endoscopic Response
timeFrame: 1 year
measure: Week 52 Outcomes: Clinical Remission and Minimal Endoscopic Activity
timeFrame: 1 year
measure: Week 52 Outcomes: Treatment Response
timeFrame: 1 year
measure: Week 52 Outcomes: Transmural ileal healing
timeFrame: 1 year
measure: Week 52 Outcomes: Transmural colonic healing
timeFrame: 1 year
measure: Week 52 Outcomes: Total Bowel Transmural healing
timeFrame: 1 year
measure: Week 52 Outcomes: Fecal Biochemical Remission
timeFrame: 1 year
measure: Week 52 Outcomes: Deep Fecal Biochemical Remission
timeFrame: 1 year
measure: Week 52 Outcomes: CRP Biochemical Remission
timeFrame: 1 year
measure: Week 52 Outcomes: CD64 Biochemical Remission
timeFrame: 1 year
measure: Week 52 Outcomes: PGA Remission
timeFrame: 1 year
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Phillip Minar, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: