Proof of Concept Trial of Vamorolone in Pediatric Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT04348890
• Recruitment Status: Withdrawn
• First Posted: April 16, 2020
• Last Update Posted: September 29, 2020
• Sponsor: ReveraGen BioPharma, Inc.
• Information provided by (Responsible Party): ReveraGen BioPharma, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pediatric Ulcerative Colitis	Drug: Vamorolone 4% suspension for oral dosing	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Open-Label, Proof-of-Concept Study of Vamorolone in Children and Adolescents With Mild-Moderately Active Ulcerative Colitis
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: September 1, 2022
• Estimated Study Completion Date: September 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Clinical Remission [ Time Frame: 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 :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

ReveraGen BioPharma, Inc.

Investigators

• Study Director: Laurie Conklin, MD; ReveraGen BioPharma

More Information

• Responsible Party: ReveraGen BioPharma, Inc.
• ClinicalTrials.gov Identifier: NCT04348890
• Other Study ID Numbers: VBP15 UC-001
• First Posted: April 16, 2020
• Last Update Posted: September 29, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases