Proof of Concept Trial of Vamorolone in Pediatric Ulcerative Colitis

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Pediatric Ulcerative Colitis
• Intervention / Treatment: Drug: Vamorolone 4% suspension for oral dosing

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm	Drug: Vamorolone 4% suspension for oral dosing; vamorolone 6 mg/kg/day orally once daily for 8 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ReveraGen BioPharma, Inc.
• Investigators: Study Director: Laurie Conklin, MD, ReveraGen BioPharma

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: VBP15 UC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No