Proof of Concept Trial of Vamorolone in Pediatric Ulcerative Colitis

Phase 1

Withdrawn

• Conditions: Pediatric Ulcerative Colitis
• Interventions: Drug: Vamorolone 4% suspension for oral dosing

• Registration Number: NCT04348890
• Lead Sponsor: ReveraGen BioPharma, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-13
• Study First Submitted QC: 2020-04-13
• Study First Posted: 2020-04-16
• Status Verified: 2020-09
• Study Start: 2020-09-01
• Last Update Submitted: 2020-09-25
• Last Update Posted: 2020-09-29
• Primary Completion: 2022-09-01
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Vamorolone 4% suspension for oral dosing	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Safety (adverse events)	From day 1 through 30 days after last dose
Change in osteocalcin, P1NP, CTX	From baseline to week 8 and week 12	Bone biomarkers
Change in serum CCL22	Baseline to Week 8 and Week 12
Change in serum trefoil factor 3	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 serum C-reactive protein	Baseline to Week 8 and Week 12
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
Mayo Score Rectal Bleeding Score of 0	Week 12
Change in fecal calprotectin	Baseline to Week 8 and Week 12
Change in serum miRNA 146b	Baseline to Week 8 and Week 12