Study to Compare the Efficacy & Safety of Ursoplus Capsules vs. UDCA vs. Placebo Among Chronic Liver Disease Patients (URSO-003)

Multi-Center, Randomized, Control, Phase IV Trial to Compare the Efficacy & Safety of Ursoplus® Capsules (UDCA 250mg & Silymarin 140mg) Versus UDCA Alone Versus Placebo Among Compensated Chronic Liver Diseased Patients

This study aims to compare the efficacy & safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA alone versus Placebo among Compensated Chronic Liver Diseased Patients

Study Overview

• Status: Recruiting
• Conditions: Chronic Liver Disease
• Intervention / Treatment: Drug: Ursoplus; Drug: UDCA 250mg; Other: Placebo

Detailed Description

Research Question:

Compare the efficacy & safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA alone versus Placebo among Compensated chronic liver diseased patients

Primary Objective:

To assess the efficacy of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA 250mg alone and versus Placebo in the reduction of total serum bilirubin, Direct serum bilirubin and elevated liver Enzymes from baseline to End of Treatment (EOT)

Secondary Objectives:

• To assess the efficacy of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA 250 mg alone and versus Placebo in reducing the degree of steatosis as measured by Vibration-controlled transient elastography with Controlled Attenuation Parameter (CAP)
• To assess the safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA 250 mg alone and versus Placebo among compensated Chronic Liver Diseased Patients
• To describe improvement in quality of life for patients after treatment

A study population of 297 patients suffering from compensated chronic Liver Disease, who will be randomized according to Vibration-controlled transient elastography in screening visit into 2 groups:

• Group 1: with non-cirrhosis, F0, F1 and F2.
• Group 2: with advanced fibrosis and cirrhosis, F3 and F4.

Each group will receive either Ursoplus® capsules (UDCA 250mg & Silymarin 140mg), or UDCA alone or Placebo, through Stratified random sampling.

Duration for enrollment: 6 months Total duration of the study/subject will be approximately: 6 months for treatment and follow-up visits including the screening visit

Subjects will be enrolled for a duration of 6 months including the screening visit

• Screening visit 1 (Treatment initiation)
• Visit 2: after 1st month, follow-up 1
• Visit 3: after 2nd month, follow-up 2
• Visit 4: after 3rd month, follow-up 3
• Visit 5: after 4th month, follow-up 4
• Visit 6: after 5th month, follow-up 5
• End of Study visit, after 6th month of treatment, follow-up 6

• Study Type: Interventional
• Enrollment (Anticipated): 297
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gamal Dr Esmat, PhD; Phone Number: +202 01222455468; Email: g_esmat@yahoo.com
• Study Contact Backup: Name: Mohamed Dr El Kassas, PhD; Phone Number: +2 01114455552-; Email: m_elkassas@yahoo.com

Study Locations

• Egypt
  • New Cairo
    • Cairo, New Cairo, Egypt
      • Recruiting
      • Air Force Specialized Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male and female patients aged ≥ 18
2. Subjects with Compensated Chronic Liver Disease, defined as child 5-7.
3. Patients with mild disturbance of liver biochemical profile (elevated Total Serum Bilirubin ≤ 3 mg/dl, or elevated Direct Serum Bilirubin ≤ 2 mg/dl, or elevated one or more of liver enzymes, up to 3 times of the normal level (Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) & Gamma Glutamyl Transpeptidase (GGT)).
4. Non-diabetic subjects and subjects with Controlled DM-type 1 and 2 patients, HbA1C up to 7.5%
5. Non-pregnant or lactating female patients
6. Subjects who are willing to sign Informed Consent Form (ICF) and ready to comply with the protocol for the duration of the study

Exclusion Criteria:

1. Subjects with a history of hypersensitivity to any of the ingredients of the medications being studied
2. Subjects with positive PCR/or antibodies to Hepatitis C in the past 6 months
3. Subjects with positive hepatitis B surface antigen (HBsAg)
4. Subjects with elevated liver enzymes more than 3 times of the normal level Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) & Gamma Glutamyl Transpeptidase (GGT).
5. Subjects with Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC).
6. Subjects with Child Pugh Score more than 7.
7. Subjects with history of bleeding varices.
8. Subjects having uncontrolled Diabetes (HbA1cmore than 7.5 %)

9. Subjects with any medical condition requiring the usage of medication that may interfere with the absorption, distribution, metabolism or excretion of the study drug such as:

   1. Bile acid sequestering agents such as cholestyramine and colestipol.
   2. Antacids containing aluminum hydroxide.
   3. Drugs affecting lipid metabolism such as estrogens, oral and hormonal contraceptives, and clofibrate (and perhaps other lipid-lowering drugs)
10. Subjects who are receiving other liver support drugs (including drugs of the study), 1 month before study initiation.
11. Subjects with auto immune liver disease taking corticosteroid or immune suppressant
12. Pregnant or breast-feeding women
13. Use of oral contraceptives in child bearing ladies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ursoplus® capsules (UDCA 250mg & Silymarin 140mg); Ursoplus® capsules: UDCA 250mg & Silymarin 140mg 2 Capsules every 12 hours	Drug: Ursoplus; Ursoplus® capsules (UDCA 250mg & Silymarin 140mg)
Active Comparator: UDCA 250mg; UDCA capsules: UDCA 250mg 2 Capsules every 12 hours	Drug: UDCA 250mg; UDCA 250mg alone
Placebo Comparator: Placebo; Placebo alone 2 Capsules every 12 hours	Other: Placebo; Placebo alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total serum bilirubin	Change in mean Total serum bilirubin from baseline (visit 1) to End of study between the 3 treatment groups	Up to 6 months
Change in Direct Serum Bilirubin	Change in mean Direct Serum Bilirubin from baseline (visit 1) to End of study between the 3 treatment groups	Up to 6 months
Change in Elevated Liver Enzymes	Change in mean AST & ALT from baseline (visit 1) to End of study between the 3 treatment groups	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved degree of Steatosis	Change in the mean score of Controlled Attenuation Parameter (CAP) from baseline (visit 1) to End of study between the 3 treatment groups, measured by Vibration-controlled transient elastography	Up to 6 months
Improved quality of life	Change in the mean Score of different items of the RAND 36-Item Health Survey between the 3 treatment groups after 3 months (visit 4) and 6 months of treatment (End of study visit).	Up to 6 months
Incidence of adverse events (AEs)	Percent of serious (SAEs)/ non-serious adverse events (AEs), including percent changes in lab tests and percent of AEs leading to permanent discontinuation of the study drug.	Up to 6 months

Collaborators and Investigators

• Sponsor: MinaPharm Pharmaceuticals
• Investigators: Principal Investigator: Gamal Dr Esmat, PhD, Air Force Specialized Hospital; Principal Investigator: Mohamed El Kassas, PhD, Helwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: April 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: URSO - 003

Drug and device information, study documents

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