Treatment of UC With Novel Therapeutics (TURTLE)

Treatment of Ulcerative Colitis With Novel Therapeutics

This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with active mild ulcerative colitis. Participation in this study will take 12 weeks long and the study is structured as a crossover study in which participants will take the study drug for 4 weeks and a placebo drug for 4 weeks in a randomized order 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis; Ulcerative Colitis Mild
• Intervention / Treatment: Drug: BRS201; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 18
• 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:

• 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
• Disease activity based on calprotectin > 200
• Allowed medications: mesalamine and sulfasalazine
• Total Mayo score of > 5
• Patients with primary sclerosing cholangitis are eligible to enroll

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
• Use of rectal therapies
• Patients who have a confirmed malignancy or cancer within 5 years
• Congenital or acquired immunodeficiencies
• Other comorbidities including: Diabetes mellitus, systemic lupus
• High likelihood of colectomy in the next 2 months
• 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 azathioprine, 6-mercaptopurine, mycophenolate mofetil, tacrolimus, cyclosporine, thalidomide, interleukin-10, interleukin-11, and Omvoh or mirikizumab-mrkz) and biologics within the past six weeks including anti-TNF agents within the past six weeks, vedolizumab within the past six weeks, ustekinumab Risankizumab), a JAKi (tofacitinib or upadacitinib), or Velsipity (etrasimod) within the past 6 weeks. (The aim is to treat people who are having disease activity and just on mesalamine.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparator: 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 repeat the previous conditions of the group that proves to be the most effective.	Drug: BRS201; Groups 1, 2, and 3 will all contain 6 subjects each, with each subject receiving active study drug and placebo in a 2:1 randomized order; 4 will receive active treatment for the first for four weeks followed by placebo for four weeks, while the remaining 2 will receive placebo for four weeks followed by active treatment for four weeks.
Placebo Comparator: Placebo Comparator: Placebo Arm; In Group 1 of the study, subjects will take oral placebo 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 placebo 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 100mg dose of cyanocobalamin at initiation. In Group 3 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.	Drug: Placebo; Groups 1, 2, and 3 will all contain 6 subjects each, with each subject receiving active study drug and placebo in a 2:1 randomized order; 4 will receive active treatment for the first for four weeks followed by placebo for four weeks, while the remaining 2 will receive placebo for four weeks followed by active treatment for four weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalization of fecal calprotectin lab measurements	The primary endpoint for this study is the capacity of study drug to normalize fecal calprotectin levels from baseline (week 0) compared to end of active treatment (4 weeks).	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 levels and fecal calprotectin	8 weeks
Partial Mayo score	Change in partial Mayo scores from baseline to end of active treatment. The partial Mayo score measures disease activity on a scale of 0 to 9, where a higher score indicates more severe disease activity and a score of 1 or less indicated remission.	4 weeks
Measurement of sulfur metabolites in urine	Analysis of urine for measurement of thiosulfate, thiocyanate, nitrate and nitrite	8 weeks
Change in fecal calprotectin lab measurements	Change 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): August 1, 2025
• Study Completion (Estimated): December 31, 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: April 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 2.0)

Drug and device information, study documents

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