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Detoxification of the Liver In PSC (Dolphin) (DOLPHIN)

Primary Purpose

Primary Sclerosing Cholangitis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
BRS201
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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). Exclusion Criteria: 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 Patients with a history of kidney stones Congenital or acquired immunodeficiencies Other comorbidities including: diabetes mellitus, systemic lupus An episode of acute cholangitis within 4 weeks of screening

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Interventional Arm

    Placebo Arm

    Arm Description

    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 4g 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.

    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 4g 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.

    Outcomes

    Primary Outcome Measures

    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).

    Secondary Outcome Measures

    Full Information

    First Posted
    April 18, 2023
    Last Updated
    April 18, 2023
    Sponsor
    Brigham and Women's Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05835505
    Brief Title
    Detoxification of the Liver In PSC (Dolphin)
    Acronym
    DOLPHIN
    Official Title
    Detoxification of the Liver in Primary Sclerosing Cholangitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    September 1, 2025 (Anticipated)
    Study Completion Date
    December 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Brigham and Women's Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study is a clinical trial being done to investigate the efficacy of drug BRS201 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Primary Sclerosing Cholangitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Model Description
    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.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    This is a double-blinded study.
    Allocation
    Randomized
    Enrollment
    28 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Interventional Arm
    Arm Type
    Active Comparator
    Arm Description
    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 4g 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.
    Arm Title
    Placebo Arm
    Arm Type
    Placebo Comparator
    Arm Description
    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 4g 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.
    Intervention Type
    Drug
    Intervention Name(s)
    BRS201
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Alkaline Phosphatase (ALP) Test Result
    Description
    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).
    Time Frame
    4 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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). Exclusion Criteria: 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 Patients with a history of kidney stones Congenital or acquired immunodeficiencies Other comorbidities including: diabetes mellitus, systemic lupus An episode of acute cholangitis within 4 weeks of screening

    12. IPD Sharing Statement

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    Detoxification of the Liver In PSC (Dolphin)

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