Efficacy of CROWN in Repair and Maintenance of the Intestinal Mucosa in Patients With CD Receiving Anti-TNF Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate CROWN's efficacy in supporting the repair and maintenance of the intestinal mucosa of patients with moderately to severely active Crohn's Disease receiving anti-Tumor Necrosis Factor (TNF) therapy (infliximab, adalimumab, certolizumab)

Detailed Description
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The purpose of this study is to evaluate the effectiveness of an orally administered nutritional intervention (CROWN) in subjects with Crohn's Disease (CD) to support Standard Of Care (SOC) treatment in the repair and maintenance of the intestinal mucosa over a 24 week period. SOC is defined as having been on a stable maintenance dose of an anti-Tumor Necrosis Factor (TNF) agent within 24 weeks of its initiation.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effectiveness of a Nutritional Intervention in Improving the Intestinal Mucosal Health Status in Subjects With Crohn's Disease (CD) Receiving Anti-TNF Therapy

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: CROWN
* Drug: CROWN Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Crohn's Disease patient who has derived clinical benefit from the Standard of Care therapy, but continues to have evidence of incomplete healing of the intestinal mucosa. Adults (18-85 years of age) with a known history of symptomatic CD confirmed by endoscopy or radiology CDAI score ≤ 350 Active endoscopic disease (SES-CD score ≥ 6) documented during the study screening phase or SES-CD score ≥ 4 if isolated ileal disease On a stable dose of infliximab, adalimumab, or certolizumab therapy for 8 weeks prior to randomization as part of SOC Able to consume oral nutrition for up to 24 weeks consisting of two 4 oz (120 ml) servings daily Able to understand the informed consent process, willing to follow study instructions and likely to complete all required visits and procedures, including the use of an electronic device to collect study data, home computer or tablet and internet access to complete online food frequency questionnaire, and undergo 2 endoscopies in a 6 month period Exclusion Criteria: Subjects with one or more of the following criteria are excluded from participation in the study: If female, subject is pregnant, nursing, or planning to become pregnant during the study period or is of childbearing potential and unable or unwilling to use a reliable form of contraception during the study Fistula known to be contributing to diarrhea Recent or current history of bowel obstruction Stricturing disease with evidence of bowel dilation proximal to stricture on imaging Anticipated need for gastrointestinal surgical therapy in the next 6 months Current treatment with a systemic corticosteroid at dose greater than 20 mg of prednisone (or equivalent) at screening Change in any antimetabolite therapy within 8 weeks prior to randomization Current treatment with antibiotics for CD (ciprofloxacin, metronidazole) at screening Current ostomy Serious infection, neoplasia or other medical conditions which would interfere with participation in the study, in the opinion of the Investigator Evidence of Clostridium difficile infection in the previous 4 weeks History of non-compliance with clinical protocols Active participation in another CD trial or received an investigational product within the past 4 weeks Diagnosis of celiac disease Known sensitivity to milk or soy protein In the Investigator's opinion, subject has any condition or situation which makes the subject unsuitable for study participation, may put the subject at significant risk, or may confound the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CROWN<br>CROWN: A nutritionally based therapy with a high protein content, formulated as a powder. Twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks | Drug: CROWN<br>* A nutritionally based therapy, formulated as a powder, administered twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks<br>|
| Placebo Comparator: CROWN Placebo<br>Placebo: An appearance and volume matched formulated powder. Twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks | Drug: CROWN Placebo<br>* Placebo, formulated as a powder, administered twice a day, preferable 1 hour before or more than 2 hours after meals, for up to 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simple Endoscopic Score - Crohn's Disease (SES-CD) | Measuring intestinal health improvement is the Week 24 change from baseline in Simple Endoscopic Score - Crohn's Disease (SES-CD) | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma amino acid level | Change from baseline in plasma amino acid levels | Week 12 and at Week 24 | 
| Quality of Life Score - Inflammatory Bowel Disease Questionnaire (IBDQ) | Change from baseline in quality of life score in IBDQ | Weeks 12 and 24 | 
| Quality of Life Score - Work Productivity Activity Index - Crohn's Disease(WPAI-CD) | Change from baseline in quality of life score in WPAI-CD | Weeks 12 and 24 | 
| Inflammatory biomarkers | Proportion of subjects with a normalization of inflammatory biomarkers (C-Reactive Protein (CRP) and fecal calprotectin) | Week 24 | 
| Endoscopic response | Proportion of subjects with endoscopic response based on SES-CD score, defined as a decrease in the SES-CD of at least 3 points from baseline, and no worsening of either component of the PRO2 (abdominal pain or liquid or soft stool frequency) | Week 24 | 
| Corticosteroid-free | Proportion of subjects who are corticosteroid-free | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Digestive System Diseases, Gastrointestinal Diseases, Intestinal Diseases, mucosal healing, inflammatory bowel disease, Medical Food, Nutritional intervention