Precision Crohn's Disease Management Utilizing Predictive Protein Panels (ENvISION)

Crohn's Disease Clinical Trial

— ENvISION  

Official title:

A Multi-Center, Prospective Study to Discover a Companion Diagnostic for Biologics Targeting TNF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04131504
• Other study ID #: 2019-0730
• Status: Completed
• Start date: October 16, 2019
• Est. completion date: October 31, 2023

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 239
• Est. completion date: October 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 22 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• IBD

Intervention

Drug:
• Infliximab
No standard dosing regimen will be used and the dose will be determined by the treating physician
• Adalimumab
No standard dosing regimen will be used and the dose will be determined by the treating physician

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	The Leona M. and Harry B. Helmsley Charitable Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Deep Remission	Sustained Deep Remission, defined as meeting all of the following at 1 year (check all that apply): no wPCDAI score of =12.5 on two consecutive visits between week 30-52; wPCDAI at week 52 is <12.5; off prednisone between weeks 30-52; endoscopic remission (SES-CD<3)	1 year
Secondary	End of Induction Outcomes: Clinical Response	Improvement of >17.5 points from baseline wPCDAI and/or Week 16 wPCDAI= <12.5 points	Week 16
Secondary	End of Induction Outcomes: Clinical Remission	wPCDAI <12.5 at Week 16	Week 16
Secondary	End of Induction Outcomes: Steroid Free Clinical Remission	wPCDAI <12.5 and off prednisone by Week 16	Week 16
Secondary	End of Induction Outcomes: Fecal Biochemical Response	Fecal calprotectin improved >50% from baseline stool (+/- 30 days from Week 16)	Week 16
Secondary	End of Induction Outcomes: Fecal Biochemical Remission	Fecal calprotectin <250µg/g at Week 16 (+/- 30 days)	Week 16
Secondary	End of Induction Outcomes: Blood CRP Biochemical Remission	CRP <0.5 mg/dL at Week 16	Week 16
Secondary	End of Induction Outcomes: Blood CD64 Biochemical Remission	nCD64 <4.5 at Week 16	Week 16
Secondary	Week 52 Outcomes: Endoscopic Response	50% reduction in SES-CD score from baseline SES-CD (if performed)	1 year
Secondary	Week 52 Outcomes: Endoscopic Remission	SES-CD <3	1 year
Secondary	Week 52 Outcomes: Minimal Endoscopic Activity	SES-CD <6 with no individual SES-CD subscore >1	1 year
Secondary	Week 52 Outcomes: Complete Intestinal Healing	SES-CD = 0	1 year
Secondary	Week 52 Outcomes: Sustained, Steroid-free Clinical Remission	wPCDAI <12.5 for all visits from weeks 30-52, off prednisone	1 year
Secondary	Week 52 Outcomes: Clinical Remission	wPCDAI <12.5 and off prednisone at last study visit	1 year
Secondary	Week 52 Outcomes: Clinical Remission and Endoscopic Response	wPCDAI <12.5 at week 52 and SES-CD>50% reduction from baseline	1 year
Secondary	Week 52 Outcomes: Clinical Remission and Minimal Endoscopic Activity	wPCDAI <12.5 at week 52 and SES-CD<6 with no individual SES-CD subscore >1	1 year
Secondary	Week 52 Outcomes: Treatment Response	continues on anti-TNF without surgery, hospitalization and off prednisone by week 16	1 year
Secondary	Week 52 Outcomes: Transmural ileal healing	ileum subscore stage 0 (score = 0) or stage 1 (score 1-3)	1 year
Secondary	Week 52 Outcomes: Transmural colonic healing	all segments of colon subscore stage 0 (score=0) or stage 1 (score 1-3)	1 year
Secondary	Week 52 Outcomes: Total Bowel Transmural healing	total ileum and colonic subscore is not greater than stage 1 on either individual score	1 year
Secondary	Week 52 Outcomes: Fecal Biochemical Remission	fecal calprotectin <250 µg/g at week 52	1 year
Secondary	Week 52 Outcomes: Deep Fecal Biochemical Remission	fecal calprotectin <150 µg/g at week 52	1 year
Secondary	Week 52 Outcomes: CRP Biochemical Remission	CRP <0.5 mg/dL at week 52	1 year
Secondary	Week 52 Outcomes: CD64 Biochemical Remission	nCD64 <4.5 at week 52	1 year
Secondary	Week 52 Outcomes: PGA Remission	physician-rated PGA is quiescent and subject is off prednisone	1 year