Detoxification of the Liver In PSC (Dolphin)

NCT05835505 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025P000196
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a clinical trial being done to investigate the efficacy of drug BRS201 (hydroxocobalamin) as a treatment in patients with primary sclerosing cholangitis. Participation in this study will take 8 weeks long and the study is structured as a cross-over 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 9 study visits, all of which will be remote. Participation will involve taking an oral medication twice daily, tracking the medication in a log, and getting blood drawn and giving a stool sample for a few lab tests throughout the study. For the lab tests, a research nurse will visit the participant in-home for the convenience of the participant.

Conditions

Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (1)

• Alkaline Phosphatase (ALP) Test Result

  The primary endpoint for this study is the capacity of BRS201 to normalize alkaline phosphatase levels from baseline (week 0) compared to end of active treatment (4 weeks).

  4 weeks

Study Arms (2)

BRS201 Arm

ACTIVE COMPARATOR

In Group 1 of the study, subjects will take oral study drug at 1.2g twice daily, PO (2.4g daily) for 4 weeks. In Group 2 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) for 4 weeks. In Group 3 of the study, subjects will take receive a one-time 5g IV dose of the study drug using the FDA-approved IV product followed by the oral study drug at 2g twice daily, PO (4g daily) for 4 weeks. In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.

Drug: BRS201

Placebo Arm

PLACEBO COMPARATOR

In Group 1 of the study, subjects will take oral placebo at 1.2g twice daily, PO (2.4g daily) for 4 weeks. In Group 2 of the study, subjects will take oral placebo at 2g twice daily, PO (4g daily) for 4 weeks. In Group 3 of the study, subjects will take receive a one-time 5g IV dose of the study drug using the FDA-approved IV product followed by the oral placebo at 2g twice daily, PO (4g daily) for 4 weeks. In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.

Drug: Placebo

Interventions

BRS201 DRUG

Groups 1, 2, 3, and 4 will all contain 7 subjects each, with each subject receiving active study drug and placebo in a randomized order; half will receive the placebo first for four weeks followed by active treatment for four weeks, while the other half will receive active treatment for four weeks followed by placebo for four weeks.

BRS201 Arm

Placebo DRUG

Groups 1, 2, 3, and 4 will all contain 7 subjects each, with each subject receiving active study drug and placebo in a randomized order; half will receive the placebo first for four weeks followed by active treatment for four weeks, while the other half will receive active treatment for four weeks followed by placebo for four weeks.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of PSC for at least 6 months based upon cholangiography (ERCP or MRCP) demonstrating intrahepatic and/or extrahepatic biliary strictures, beading or irregularity consistent with PSC.
• ALP \> 1.5 times the upper limit of normal (ULN) at screening.
• Subject must either be on a stable dose of ursodeoxycholic acid for \> 6 months prior to screening or have been discontinued \> 4 weeks prior to screening (enrollment of patients who are on UDCA will be limited to 60% of all enrolled patients).

You may not qualify if:

• Anticipated need for liver transplant within one year as determined by Mayo PSC risk score
• Evidence of decompensated liver disease such as variceal bleeding, ascites, or hepatic encephalopathy.
• Evidence of advanced liver disease including MELD score \> 10, bilirubin \> 3.0, platelet count \< 100,000; or INR \> 1.4
• Concomitant chronic liver disease including alcohol related liver disease, chronic hepatitis B or C infection, haemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency, non-alcoholic steatohepatitis, autoimmune hepatitis, or primary biliary cholangitis
• Secondary causes of sclerosing cholangitis
• Patients who have a confirmed malignancy or cancer within 5 years except non-melanoma skin cancers
• Treatment with any investigational agents, within two months or 5 half-lives of the investigational product, whichever is longer.
• Active illicit drug or more than moderate alcohol consumption.
• Evidence of bacterial cholangitis within 6 months of enrollment
• In patients with Ulcerative Colitis, or, if Crohn's disease, a need for additional therapy at time of screening.
• Chronic kidney injury (eGFR \< 60)
• Pregnancy or lactation
• Uncontrolled hypertension with a systolic BP \> 140 and a systolic BP \> 90
• Prohibited medications: current use of vitamin C and prednisone
• Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, 02467, United States

RECRUITING

MeSH Terms

Conditions

Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Joshua A Korzenik, MD

  Brigham and Womens Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sophie Mitchell, BS

CONTACT

5089363674; smitchell22@bwh.harvard.edu

Siani Ellis, BS

CONTACT

6177325500; pscresearch@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blinded study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Crohn's and Colitis Center

Model Details: This a crossover study in which everyone will have a period of time on the active medication and a period of time on the placebo.

Study Record Dates

• First Submitted: April 18, 2023
• First Posted: April 28, 2023
• Study Start: December 12, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (1)