Novel therapeutics for acute ulcerative colitis

Study of Novel Therapeutics for Acute Remedy of Colitis

This trial tests an oral (and sometimes IV) drug called BRS201 in adults with severe ulcerative colitis who have not improved with standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Drugs / interventions: Upadacitinib, Tofacitinib, prednisone
• Locations: 2 sites (Chestnut Hill, Massachusetts and 1 other locations)
• Trial ID: NCT06420492 on ClinicalTrials.gov

What this trial studies

This is an open-label phase 2 pilot testing BRS201 over a 12-week participation period with four weeks of active oral dosing (twice daily) and an optional IV dose. Participants will attend eight on-site visits for safety monitoring, blood draws, and collection of stool and urine samples, and may undergo flexible sigmoidoscopy at baseline and end of treatment. Eligible patients include adults with a confirmed diagnosis of UC for more than three months, extensive colonic involvement (≥15 cm), and an acute severe flare that has not responded to prednisone. Concomitant stable doses of certain biologics or JAK inhibitors are allowed if dosing has been stable for the required lead-in periods.

Who should consider this trial

Good fit: Adults with confirmed ulcerative colitis of at least three months' duration, ≥15 cm colonic involvement, currently experiencing an acute severe flare and who have failed an adequate course of prednisone are the ideal candidates.

Not a fit: Patients with mild disease, very recent diagnosis, unstable doses of permitted concomitant therapies, or contraindications to the drug or study procedures are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, BRS201 could provide a new treatment option to reduce symptoms and induce remission in adults with severe, treatment-refractory ulcerative colitis.

How similar studies have performed: BRS201 itself appears to be a novel agent with limited published clinical data, although other drug classes such as biologics and JAK inhibitors have shown benefit in refractory ulcerative colitis.

Eligibility criteria

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
* Patients with primary sclerosing cholangitis are eligible to enroll
* Patients will have failed 5 days of oral prednisone 30 mg or greater for 5 days and still having a SCCAI of \> 6
* Patients who are taking 20mg or less of oral prednisone and plan to stay at that dose during their participation in the study
* Accepted medications:

  * Anti-TNF agents are permissible if the patient has been taking them for at least 10 weeks and anticipates to maintain a steady for the duration of the study.
  * Rinvoq (Upadacitinib) is permissible if the subject has been taking this medication for at least 4 weeks and anticipates to maintain a steady dose for the duration of the study.
  * Xeljanz (Tofacitinib) is permissible if the subject has been taking this medication for at least 4 weeks and anticipates to maintain a steady dose for the duration of the study.
  * Other biologics are permissible if the subject has been taking the medication for at least 10 weeks and anticipates to maintain a steady dose for the duration of the study

Exclusion Criteria:

* History of uncontrolled hypertension with systolic BP \> 140 and systolic BP \> 90
* Chronic kidney disease as defined by GFR \<55mL/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:

  * Rinvoq (Upadacitinib): Subjects will be excluded from this study if their last dose of this medication was administered within 4 weeks. If subjects have stopped taking this medication and their last dose was administered more than 4 weeks prior to enrollment, they will be eligible for participation.
  * Xeljanz (Tofacitinib): Subjects will be excluded from this study if their last dose of this medication was administered within 4 weeks. If subjects have stopped taking this medication and their last dose was administered more than 4 weeks prior to enrollment, they will be eligible for participation.
  * Other Medications: Subjects will be excluded from this study if they stopped taking any other medications for ulcerative colitis within 8 weeks. If subjects have stopped taking the medication and their last dose was more than 8 weeks prior to enrollment, they will be eligible for participation.

Where this trial is running

Chestnut Hill, Massachusetts and 1 other locations

• Brigham and Women's Hospital — Chestnut Hill, Massachusetts, United States (Not_yet_recruiting)
• Brigham and Women's Hospital — Chestnut Hill, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Joshua Korzenik, MD

Conditions Ulcerative Colitis; Ulcerative Colitis Chronic Moderate; Ulcerative Colitis Chronic Severe