Pediatric Ulcerative Colitis
Conditions
Brief summary
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.
Interventions
DRUGVamorolone 4% suspension for oral dosing
vamorolone 6 mg/kg/day orally once daily for 8 weeks.
Sponsors
ReveraGen BioPharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Mayo Score Rectal Bleeding Score of 0 | Week 12 | — |
| Change in fecal calprotectin | Baseline to Week 8 and Week 12 | — |
| Safety (adverse events) | From day 1 through 30 days after last dose | — |
| Change in serum C-reactive protein | Baseline to Week 8 and Week 12 | — |
| Cushingoid appearance | Week 8 and Week 12 | Physician reported, yes or no |
| Week 8 response | Baseline to 8 Weeks and 12 Weeks | Decrease in PUCAI score by 20 points or more (lower scores indicate less severe disease activity) |
| Change in Mayo Score Stool Frequency subscore | Baseline to 8 Weeks and 12 Weeks | Score ranges from 0-3, with lower scores indicating less severe disease activity |
| Change in Mayo rectal bleeding score | Baseline to 8 Weeks and 12 Weeks | Scores range from 0-3, with lower scores indicating less severe disease activity |
| Mayo Score Stool Frequency subscore of 0 or 1 | Week 12 | — |
| Change in osteocalcin, P1NP, CTX | From baseline to week 8 and week 12 | Bone biomarkers |
Outcome results
None listed