Ulcerative Colitis, Ulcerative Colitis Chronic Moderate, Ulcerative Colitis Chronic Severe
Conditions
Brief summary
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 8 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.
Interventions
DRUGBRS201
Groups 1, 2, 3, and 4 will all contain 5 subjects each, with each subject receiving active study drug for four weeks.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label study in which everyone will receive active treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sulfur Metabolism | 4 weeks | The primary measure of dose response will be urinary measures of sulfur metabolism including a \> 50% reduction from pretreatment levels sulfate, and thiosulfate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma nitrite, nitrate, or nitrosothiol | 8 weeks | Correlation between changes in plasma nitrite, nitrate or nitrosothiol level in relation to calprotectin |
| Normalization of fecal calprotectin lab measurements | 8 weeks | 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. |
| Reduction in fecal calprotectin lab measurements | 4 weeks | Reduction in fecal calprotectin to \< ULN at the end of active treatment |
| Simple Clinical Colitis Activity Index (SCCAI) | 12 weeks | 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. |
| Tissue Analysis | 4 weeks | Analysis of tissue metabolomics and proteomics at day 0 vs day 28; |
| Mitochondria evaluation | 12 weeks | Changes in mitochondria on EM evaluation |
| Urine Assays | 12 weeks | Urine levels for thiosulfate, thiocyanate, nitrate and nitrite; |
| Mayo Score | 4 weeks | 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). |
Countries
United States
Contacts
Primary ContactJoshua Korzenik, MD
Backup ContactSiani Ellis
Outcome results
None listed