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A Study Evaluating the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Primary Sclerosing Cholangitis

Primary Purpose

Primary Sclerosing Cholangitis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Aramchol meglumine
Sponsored by
Galmed Research and Development, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis

Eligibility Criteria

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

Inclusion Criteria: Male or female age 18 years and above (inclusive at first screening visit) Established diagnosis of large duct PSC based on abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP) or Endoscopic retrograde cholangiopancreatography (ERCP) Alkaline phosphatase > 150 IU/l Stable inflammatory bowel disease therapy > 3months for IBD patients If receiving treatment with Ursodeoxycholic acid (UDCA; ursodiol), therapy is at a dose of <20 mg/kg/day, has been stable for at least 6 months before screening Ability to understand the nature of the study and to sign a written informed consent form (ICF) Exclusion Criteria: Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically Active Crohn's disease (CDAI > 40) or ulcerative colitis (Mayo IBD score > 4) or active non-hemorrhoidal rectal bleeding Small bowel resection > 100 cm Cirrhosis (clinically evident or by biopsy) Prior hepatic decompensation event Recent (< 6 weeks) acute cholangitis or hospitalization for PSC or IBD Bleeding diathesis or other contraindication for liver biopsy Known GI or hepatobiliary malignancy Prior liver transplantation Prior exposure to study drug Active untreated viral hepatitis or other concomitant liver disease

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    PSC patients administered with Aramchol meglumine

    PSC patients administered with placebo

    Arm Description

    Adult subjects with clinically diagnosed PSC that are administered with Aramchol meglumine

    Adult subjects with clinically diagnosed PSC that are administered with matching placebo

    Outcomes

    Primary Outcome Measures

    Change from Baseline in serum alkaline phosphatase (ALP)
    The change from Baseline to Week 48 in ALP levels

    Secondary Outcome Measures

    Change from Baseline in hepatobiliary fibrosis using the Nakanuma staging scale
    Change from Baseline to Week 48 in liver histology using the Nakanuma stage classification. A score of 0 is classified as stage 1 (no or minimal disease progression), while 1 score 5 or 6 is classified as stage 4 (advanced disease progression).
    Change from Baseline in Enhanced liver fibrosis (ELF)
    Change from Baseline to Week 48 in Enhanced liver fibrosis (ELF) test. Score below 7.7 indicate no to mild fibrosis, and score higher than 11.3 indicate cirrhosis.
    Change from Baseline in MRCP
    Change from Baseline to Week 48 in magnetic resonance cholangiopancreatography (MRCP)
    Change from Baseline in quantitative liver function using Gadoxetate clearance
    Change from Baseline to Week 48 in quantitative liver function using Gadoxetate clearance
    Change from Baseline in 5D-itch scale
    Change from Baseline to Week 48 in the 5 dimension itch scale (5d-itch scale) measuring pruritus (the 5 dimensions are degree, duration, direction, disability and distribution). Higher degree mean worse outcome <8 on rating scale mean no pruritus, and >22 on rating scale indicate severe pruritus
    Change from Baseline to Week 48 in Patient-Reported Outcomes Measurement Information System (PROMIS)-19 score
    Change from Baseline to Week 48 in the Patient-Reported Outcomes Measurement Information System (PROMIS)-19 questionnaire score. The average score for Physical Function is 50, with a score of 40 considered below average and a score of 60 considered above average
    Change from Baseline in the Mayo IBD symptom severity score
    Change from Baseline to Week 48 in the Mayo Inflammatory bowel disease (IBD) symptom severity score. A score of 3 to 5 points indicates mildly active disease and a score of 11 to 12 points indicates severely active bowel disease
    Change from Baseline in the revised Mayo risk score (rMRS)
    Change from Baseline to Week 48 in the revised Mayo risk score (rMRS). The score provide the estimated probability of survival (%) based on age, bilirubin, AST, and history of bleeding
    Change from Baseline in the UK-PSC score
    Change from Baseline to Week 48 in the united kingdom primary sclerosing cholangitis (UK-PSC) score. The score provide the estimated probability of survival (%) based on age, bilirubin, albumin, platelets, hemoglobin and ALP
    Change from Baseline in the PSC risk estimate tool (PREsTo)
    Change from Baseline to Week 48 in the PSC risk estimate tool (PREsTo). The tool consists of bilirubin, albumin, ALP, platelets, AST, hemoglobin, sodium, patient age and the number of years since PSC was diagnosed, and it predicts short-term and long-term need for liver transplantation or death.

    Full Information

    First Posted
    October 11, 2023
    Last Updated
    October 17, 2023
    Sponsor
    Galmed Research and Development, Ltd.
    Collaborators
    Virginia Commonwealth University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06095986
    Brief Title
    A Study Evaluating the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Primary Sclerosing Cholangitis
    Official Title
    A Proof of Concept, Prospective, Randomized, Placebo-controlled, Double-blind, Study to Evaluate the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Patients With Primary Sclerosing Cholangitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2024 (Anticipated)
    Primary Completion Date
    September 2025 (Anticipated)
    Study Completion Date
    December 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Galmed Research and Development, Ltd.
    Collaborators
    Virginia Commonwealth University

    4. Oversight

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

    5. Study Description

    Brief Summary
    The objectives of this study is to Evaluate the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Patients with Primary Sclerosing Cholangitis
    Detailed Description
    The objectives of this study are to: Establish the safety and tolerability of once daily (QD) Aramchol meglumine in patients with PSC Examine whether once daily (QD) Aramchol meglumine has any effect on serum alkaline phosphatase Provide a comprehensive readout of clinical efficacy following once daily (QD) Aramchol meglumine administration

    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
    Parallel Assignment
    Model Description
    Parallel group analysis
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    Double-blind
    Allocation
    Randomized
    Enrollment
    24 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    PSC patients administered with Aramchol meglumine
    Arm Type
    Active Comparator
    Arm Description
    Adult subjects with clinically diagnosed PSC that are administered with Aramchol meglumine
    Arm Title
    PSC patients administered with placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Adult subjects with clinically diagnosed PSC that are administered with matching placebo
    Intervention Type
    Drug
    Intervention Name(s)
    Aramchol meglumine
    Intervention Description
    Aramchol meglumine is derived from a weak acid (Aramchol) and an amino-sugar (meglumine)
    Primary Outcome Measure Information:
    Title
    Change from Baseline in serum alkaline phosphatase (ALP)
    Description
    The change from Baseline to Week 48 in ALP levels
    Time Frame
    48 weeks
    Secondary Outcome Measure Information:
    Title
    Change from Baseline in hepatobiliary fibrosis using the Nakanuma staging scale
    Description
    Change from Baseline to Week 48 in liver histology using the Nakanuma stage classification. A score of 0 is classified as stage 1 (no or minimal disease progression), while 1 score 5 or 6 is classified as stage 4 (advanced disease progression).
    Time Frame
    48 weeks
    Title
    Change from Baseline in Enhanced liver fibrosis (ELF)
    Description
    Change from Baseline to Week 48 in Enhanced liver fibrosis (ELF) test. Score below 7.7 indicate no to mild fibrosis, and score higher than 11.3 indicate cirrhosis.
    Time Frame
    48 weeks
    Title
    Change from Baseline in MRCP
    Description
    Change from Baseline to Week 48 in magnetic resonance cholangiopancreatography (MRCP)
    Time Frame
    48 weeks
    Title
    Change from Baseline in quantitative liver function using Gadoxetate clearance
    Description
    Change from Baseline to Week 48 in quantitative liver function using Gadoxetate clearance
    Time Frame
    48 weeks
    Title
    Change from Baseline in 5D-itch scale
    Description
    Change from Baseline to Week 48 in the 5 dimension itch scale (5d-itch scale) measuring pruritus (the 5 dimensions are degree, duration, direction, disability and distribution). Higher degree mean worse outcome <8 on rating scale mean no pruritus, and >22 on rating scale indicate severe pruritus
    Time Frame
    48 weeks
    Title
    Change from Baseline to Week 48 in Patient-Reported Outcomes Measurement Information System (PROMIS)-19 score
    Description
    Change from Baseline to Week 48 in the Patient-Reported Outcomes Measurement Information System (PROMIS)-19 questionnaire score. The average score for Physical Function is 50, with a score of 40 considered below average and a score of 60 considered above average
    Time Frame
    48 weeks
    Title
    Change from Baseline in the Mayo IBD symptom severity score
    Description
    Change from Baseline to Week 48 in the Mayo Inflammatory bowel disease (IBD) symptom severity score. A score of 3 to 5 points indicates mildly active disease and a score of 11 to 12 points indicates severely active bowel disease
    Time Frame
    48 weeks
    Title
    Change from Baseline in the revised Mayo risk score (rMRS)
    Description
    Change from Baseline to Week 48 in the revised Mayo risk score (rMRS). The score provide the estimated probability of survival (%) based on age, bilirubin, AST, and history of bleeding
    Time Frame
    48 weeks
    Title
    Change from Baseline in the UK-PSC score
    Description
    Change from Baseline to Week 48 in the united kingdom primary sclerosing cholangitis (UK-PSC) score. The score provide the estimated probability of survival (%) based on age, bilirubin, albumin, platelets, hemoglobin and ALP
    Time Frame
    48 weeks
    Title
    Change from Baseline in the PSC risk estimate tool (PREsTo)
    Description
    Change from Baseline to Week 48 in the PSC risk estimate tool (PREsTo). The tool consists of bilirubin, albumin, ALP, platelets, AST, hemoglobin, sodium, patient age and the number of years since PSC was diagnosed, and it predicts short-term and long-term need for liver transplantation or death.
    Time Frame
    48 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female age 18 years and above (inclusive at first screening visit) Established diagnosis of large duct PSC based on abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP) or Endoscopic retrograde cholangiopancreatography (ERCP) Alkaline phosphatase > 150 IU/l Stable inflammatory bowel disease therapy > 3months for IBD patients If receiving treatment with Ursodeoxycholic acid (UDCA; ursodiol), therapy is at a dose of <20 mg/kg/day, has been stable for at least 6 months before screening Ability to understand the nature of the study and to sign a written informed consent form (ICF) Exclusion Criteria: Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically Active Crohn's disease (CDAI > 40) or ulcerative colitis (Mayo IBD score > 4) or active non-hemorrhoidal rectal bleeding Small bowel resection > 100 cm Cirrhosis (clinically evident or by biopsy) Prior hepatic decompensation event Recent (< 6 weeks) acute cholangitis or hospitalization for PSC or IBD Bleeding diathesis or other contraindication for liver biopsy Known GI or hepatobiliary malignancy Prior liver transplantation Prior exposure to study drug Active untreated viral hepatitis or other concomitant liver disease
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yossi Gilgun-Sherki, PhD, MBA
    Phone
    +972543314054
    Email
    yossigs@galmedpharma.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Arun Sanyal, MD
    Organizational Affiliation
    The Sanyal Institute for Liver Disease & Metabolic Health at VCU
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Share the study protocol and SAP
    IPD Sharing Time Frame
    Study completion
    IPD Sharing Access Criteria
    Any person with access to ClinicalTrials.gov

    Learn more about this trial

    A Study Evaluating the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Primary Sclerosing Cholangitis

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