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

Study Overview
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Brief Summary
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The objectives of this study is to Evaluate the Safety, Tolerability, and Efficacy of Aramchol Meglumine in Patients with Primary Sclerosing Cholangitis

Detailed Description
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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

Official Title
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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

Conditions
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Primary Sclerosing Cholangitis

Intervention / Treatment
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* Drug: Aramchol meglumine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group analysis
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PSC patients administered with Aramchol meglumine<br>Adult subjects with clinically diagnosed PSC that are administered with Aramchol meglumine | Drug: Aramchol meglumine<br>* Aramchol meglumine is derived from a weak acid (Aramchol) and an amino-sugar (meglumine)<br>|
| Placebo Comparator: PSC patients administered with placebo<br>Adult subjects with clinically diagnosed PSC that are administered with matching placebo | Drug: Aramchol meglumine<br>* Aramchol meglumine is derived from a weak acid (Aramchol) and an amino-sugar (meglumine)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in serum alkaline phosphatase (ALP) | The change from Baseline to Week 48 in ALP levels | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 48 weeks | 
| 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. | 48 weeks | 
| Change from Baseline in MRCP | Change from Baseline to Week 48 in magnetic resonance cholangiopancreatography (MRCP) | 48 weeks | 
| Change from Baseline in quantitative liver function using Gadoxetate clearance | Change from Baseline to Week 48 in quantitative liver function using Gadoxetate clearance | 48 weeks | 
| 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 | 48 weeks | 
| 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 | 48 weeks | 
| 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 | 48 weeks | 
| 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 | 48 weeks | 
| 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 | 48 weeks | 
| 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. | 48 weeks |