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

Primary Sclerosing Cholangitis Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06095986
• Other study ID #: AM-002
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: December 2026

Study information

• Verified date: October 2023
• Source: Galmed Pharmaceuticals Ltd
• Contact: Yossi Gilgun-Sherki, PhD, MBA
• Phone: +972543314054
• Email: yossigs[@]galmedpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: December 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Aramchol meglumine
Aramchol meglumine is derived from a weak acid (Aramchol) and an amino-sugar (meglumine)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Galmed Research and Development, Ltd.	Virginia Commonwealth University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in serum alkaline phosphatase (ALP)	The change from Baseline to Week 48 in ALP levels	48 weeks
Secondary	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
Secondary	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
Secondary	Change from Baseline in MRCP	Change from Baseline to Week 48 in magnetic resonance cholangiopancreatography (MRCP)	48 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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