Study of Novel Therapeutics for Acute Remedy of Colitis (SHARC)

This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with acute ulcerative colitis. Patients who qualify are adults who have not responded to treatments for their severe ulcerative colitis. Participation in this study will take 12 weeks long and the study is structured as an open-label pilot study in which participants will take the study drug for 4 weeks in the form of an oral medication. Participation may also involve receiving an IV dose of the medication. The study will require participants to attend 7 study visits, all of which will be conducted at a study site. Participation will involve taking an oral medication twice daily, tracking the medication in a log, and getting blood drawn and giving a stool and urine sample for a few lab tests throughout the study. Participants may also undergo a flexible sigmoidoscopy at the beginning and end of the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis; Ulcerative Colitis Chronic Moderate; Ulcerative Colitis Chronic Severe
• Intervention / Treatment: Drug: BRS201

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joshua Korzenik, MD; Phone Number: 617 732-6389; Email: jkorzenik@bwh.harvard.edu
• Study Contact Backup: Name: Siani Ellis; Phone Number: 617-396-7703; Email: sellis13@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital
      • Principal Investigator: Joshua Korzenik, MD
      • Contact: Sophie Mitchell; Email: smitchell22@bwh.harvard.edu
      • Contact: Siani Ellis; Phone Number: 617-396-7703; Email: sellis13@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Severe outpatient or hospitalized for an acute UC flare
• Ability to give consent
• Patients with a confirmed diagnosis of UC for > 3 months
• History of ≥ 15 cm of colonic involvement as confirmed by colonoscopy
• Total Mayo score of > 6
• Patients with primary sclerosing cholangitis are eligible to enroll
• Patients will have failed 3 days of IV steroids or 5 days of oral prednisone 30 mg or greater for 5 days and still having a SCCAI of > 6
• Anticipated to be administered ustekinumab, vedolizumab or 6-MP/azathioprine as their subsequent medication.

Exclusion Criteria:

• History of uncontrolled hypertension with systolic BP > 140 and systolic BP > 90
• Chronic kidney disease as defined by GFR <60mL/min
• Impaired hepatic function (transaminases elevated > 2.5 x ULN) unless due to PSC
• Evidence of C. difficile (Negative test result within 1 month is acceptable)
• Infectious Colitis or drug induced colitis
• Crohn's Disease or Indeterminate colitis
• Decompensated liver disease
• Patients who are pregnant or breastfeeding
• Patients who have a confirmed malignancy or cancer within 5 years
• Congenital or acquired immunodeficiencies
• Other comorbidities including: Diabetes mellitus, systemic lupus
• Participation in a therapeutic clinical trial in the preceding 30 days or simultaneously during this trial
• Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease
• Prohibited medications: Vitamin C, prednisone, immune modulators (including but not limited to, mycophenolate mofetil, tacrolimus, cyclosporine, thalidomide, interleukin-10 and interleukin-11) and anti-TNF agents within the past six weeks
• Patients are planned to be started on a fast- acting medication including an anti-TNF agent (infliximab, adalimumab, golimumab, certolizumab), on a JAKi (upadacitinib, tofacitinib)

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: BRS201 Arm; In Group 1 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks. In Group 2 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks. Subjects will also receive a one time 2.5g dose of study drug at initiation. In Group 3 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks. Subjects will also receive one 2.5g dose of study drug at initiation and a second 2.5g intravenous dose of study drug at week 2.

Drug: BRS201; Groups 1, 2, and 3 will all contain 5 subjects each, with each subject receiving active study drug for four weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mayo Score	The primary endpoint for this study is change in Total Mayo Score with improvement being a reduction in 3 points and remission being a score of 0 or 1 from day 0 to end of week 4 (at second flexible sigmoidoscopy).	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simple Clinical Colitis Activity Index (SCCAI)	Clinical symptoms assessed by SCCAI which measures patient reported outcomes on a scale of 0 to 19, where a higher score indicates more severe activity and active disease is a score of 5 or more.	12 weeks
Plasma nitrite, nitrate, or nitrosothiol	Correlation between changes in plasma nitrite, nitrate or nitrosothiol level in relation to calprotectin	8 weeks
Normalization of fecal calprotectin lab measurements	The capacity of study drug to normalize fecal calprotectin levels from baseline (week 0) compared to end of active treatment (4 weeks) and at week 6.	8 weeks
Reduction in fecal calprotectin lab measurements	Reduction in fecal calprotectin to < ULN at the end of active treatment	4 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

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: Unknown (Pending approval)

Drug and device information, study documents

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