Proof of Concept Trial of Vamorolone in Pediatric Ulcerative Colitis

Study Overview
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Brief Summary
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This is a Phase I/II, multi-center, open-label proof-of-concept study of vamorolone. Twenty participants with a flare of mild or moderately active Ulcerative Colitis (defined as a Pediatric Ulcerative Colitis Activity Index [PUCAI] 10-60) will be enrolled and receive vamorolone 6 mg/kg/day orally once daily for 8 weeks.

Official Title
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A Phase I/II Open-Label, Proof-of-Concept Study of Vamorolone in Children and Adolescents With Mild-Moderately Active Ulcerative Colitis

Conditions
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Pediatric Ulcerative Colitis

Intervention / Treatment
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* Drug: Vamorolone 4% suspension for oral dosing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has provided written informed consent/Health Insurance Portability and Accountability Act (HIPAA) authorization prior to any study-related procedures; Subject has current mild to moderately active ulcerative colitis, defined as a PUCAI score of 10-60. Subject is ≥ 4 years old and <18 years old at the time of enrollment. Subject has had 1) a colonoscopy demonstrating endoscopic and histologic inflammation, and/or; 2) a fecal calprotectin > 250 mcg/g, in the preceding 1 month. Subject is willing and able to comply with scheduled visits, study drug administration plan, and study procedures. Subject has not started a new immunomodulator or biologic in the preceding 2 months. If subject is taking an immunomodulator and/or biologic, the dose has not been changed in the last 2 months Subject has a positive varicella IgG titer, or history of at least 2 documented varicella vaccines Exclusion Criteria: Subject is currently being treated or has received previous treatment with oral or rectal glucocorticoids (including budesonide) in the past month Subject has an allergy or hypersensitivity to the study medication or to any of its constituents Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator Subject is taking any other investigational drug currently or has taken any other investigational drug within 3 months prior to the start of study treatment Clinically significant abnormal biochemical and hematological parameters, including: Neutrophil count < 1000 cells/mm3 Platelet count ≤ 130 cells/mm3 Creatinine ≥ 1.2 x the upper limit of normal Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2x the upper limit of normal Conjugated bilirubin greater than 1.2. mg/dL Has active infection with enteric pathogens (including C. difficile) Has a positive PPD, Quantiferon Gold, or Interferon-gamma assay Is pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br> | Drug: Vamorolone 4% suspension for oral dosing<br>* vamorolone 6 mg/kg/day orally once daily for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Pediatric Ulcerative Colitis Activity Index score <10 and no additional therapy or colectomy). The PUCAI is scored from 0-85, lower numbers indicate less severe disease activity. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (adverse events) |  | From day 1 through 30 days after last dose | 
| Change in osteocalcin, P1NP, CTX | Bone biomarkers | From baseline to week 8 and week 12 | 
| Cushingoid appearance | Physician reported, yes or no | Week 8 and Week 12 | 
| Week 8 response | Decrease in PUCAI score by 20 points or more (lower scores indicate less severe disease activity) | Baseline to 8 Weeks and 12 Weeks | 
| Change in Mayo Score Stool Frequency subscore | Score ranges from 0-3, with lower scores indicating less severe disease activity | Baseline to 8 Weeks and 12 Weeks | 
| Change in Mayo rectal bleeding score | Scores range from 0-3, with lower scores indicating less severe disease activity | Baseline to 8 Weeks and 12 Weeks | 
| Mayo Score Stool Frequency subscore of 0 or 1 |  | Week 12 | 
| Mayo Score Rectal Bleeding Score of 0 |  | Week 12 | 
| Change in fecal calprotectin |  | Baseline to Week 8 and Week 12 | 
| Change in serum C-reactive protein |  | Baseline to Week 8 and Week 12 | 
| Change in serum CCL22 |  | Baseline to Week 8 and Week 12 | 
| Change in serum miRNA 146b |  | Baseline to Week 8 and Week 12 | 
| Change in serum trefoil factor 3 |  | Baseline to Week 8 and Week 12 |