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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Aramchol meglumine

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

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yossi Gilgun-Sherki, PhD, MBA; Phone Number: +972543314054; Email: yossigs@galmedpharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female age 18 years and above (inclusive at first screening visit)
2. Established diagnosis of large duct PSC based on abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP) or Endoscopic retrograde cholangiopancreatography (ERCP)
3. Alkaline phosphatase > 150 IU/l
4. Stable inflammatory bowel disease therapy > 3months for IBD patients
5. 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
6. Ability to understand the nature of the study and to sign a written informed consent form (ICF)

Exclusion Criteria:

1. Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically
2. Active Crohn's disease (CDAI > 40) or ulcerative colitis (Mayo IBD score > 4) or active non-hemorrhoidal rectal bleeding
3. Small bowel resection > 100 cm
4. Cirrhosis (clinically evident or by biopsy)
5. Prior hepatic decompensation event
6. Recent (< 6 weeks) acute cholangitis or hospitalization for PSC or IBD
7. Bleeding diathesis or other contraindication for liver biopsy
8. Known GI or hepatobiliary malignancy
9. Prior liver transplantation
10. Prior exposure to study drug
11. Active untreated viral hepatitis or other concomitant liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Galmed Research and Development, Ltd.
• Collaborators: Virginia Commonwealth University
• Investigators: Principal Investigator: Arun Sanyal, MD, The Sanyal Institute for Liver Disease & Metabolic Health at VCU

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: AM-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No