HTD1801 in Adults With Nonalcoholic Steatohepatitis and Liver Fibrosis Who Have Type 2 Diabetes or Pre-Diabetes

Type 2 Diabetes Clinical Trial

— CENTRICITY  

Official title:

A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of HTD1801 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis Who Have Type 2 Diabetes (T2DM) or Pre-Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05623189
• Other study ID #: HTD1801.PCT014
• Secondary ID: The CENTRICITY S
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 27, 2022
• Est. completion date: May 31, 2025

Study information

• Verified date: September 2023
• Source: HighTide Biopharma Pty Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 2b, multicenter, randomized, double-blind, placebo-controlled study of HTD1801 in adult subjects with non-alcoholic steatohepatitis and liver fibrosis who have type 2 diabetes mellitus or pre-diabetes.

Description:

This phase 2b, double-blind, randomized, placebo-controlled, multicenter study will evaluate the effect of HTD1801, 1250 mg twice daily (BID) compared to placebo BID on histologic improvements in adult subjects with non-alcoholic steatohepatitis and liver fibrosis who have type 2 diabetes mellitus or pre-diabetes. The study will enroll approximately 210 subjects with biopsy-confirmed non-alcoholic steatohepatitis and evidence of stage 2 or stage 3 liver fibrosis. Subjects will receive investigational product for up to 60 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 218
• Est. completion date: May 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion criteria:

• Clinical diagnosis of non-alcoholic steatohepatitis (NASH) upon central read of a liver biopsy obtained no more than 6 months before Day 0.
• Histologic evidence of fibrosis stage 2 or stage 3 as defined by the non-alcoholic steatohepatitis (NASH) clinical research network (CRN) scoring of fibrosis.
• Clinically documented diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening or prediabetes at screening.
• BMI >25 kilograms/meters squared (>23 kilograms/meters squared if Asian).

Key Exclusion criteria:

• Fibrosis stage 4.
• History of alcohol or substance abuse or dependence.
• Liver disease unrelated to non-alcoholic steatohepatitis.
• History of significant cardiovascular disease.
• History of type 1 diabetes.
• Inability or unwillingness to undergo 2 planned liver biopsies OR 1 planned biopsy if historical liver biopsy was used to confirm eligibility at entry.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Fatty Liver
• Liver Cirrhosis
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis (NASH)
• Prediabetic State
• Type 2 Diabetes

Intervention

Drug:
• HTD1801
HTD1801,1250 mg, BID
• Placebo
Placebo, BID

Locations

Country	Name	City	State
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou	Zhejiang
China	Nanjing Drum Tower Hospital - the Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
Hong Kong	Humanity and Health Clinical Trial Centre Lt.	Hong Kong
Hong Kong	Chinese University of Hong Kong Prince of Wales Hospital	Shatin
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Piedmont Health Care	Atlanta	Georgia
United States	Pinnacle Clinical Research	Austin	Texas
United States	Mercy Medical Center	Baltimore	Maryland
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	South Texas Research Institute	Brownsville	Texas
United States	San Fernando Valley Health Institute	Canoga Park	California
United States	The Institute for Liver Health (Arizona Liver Health)	Chandler	Arizona
United States	ClinSearch LLC	Chattanooga	Tennessee
United States	Epic Medical Research	Chickasha	Oklahoma
United States	Premier Research	Clarksville	Tennessee
United States	Tampa Bay Medical Research, Inc.	Clearwater	Florida
United States	EPIC Medical Research	DeSoto	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Covenant Metabolic Specialists - Fort Meyers	Fort Myers	Florida
United States	Clinnova Research Solutions	Garden Grove	California
United States	Pinnacle Research, Georgetown TX	Georgetown	Texas
United States	Evolution Clinical Trials, Inc.	Hialeah Gardens	Florida
United States	Jubilee Clinical Research, Inc.	Las Vegas	Nevada
United States	Louisvill Metabolic and Atherosclerosis Research Center (L-MARC)	Louisville	Kentucky
United States	ClinCloud LLC Maitland	Maitland	Florida
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Clinical Pharmacology of Miami, LLC	Miami	Florida
United States	Floridain Clinical Research	Miami Lakes	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Catalina Research Institute	Montclair	California
United States	Lucas Research - Diabetes and Endocrinology	Morehead City	North Carolina
United States	Tandem Clinical Research GI - New York	New York	New York
United States	Liver Institute of Virginia	Newport News	Virginia
United States	California Liver Institute	Pasadena	California
United States	Arizona Liver Health - Glendae	Peoria	Arizona
United States	Inland Empire Liver Foundation	Rialto	California
United States	The Liver Institute of Virginia	Richmond	Virginia
United States	Pinnacle Clinical Research San Antonio	San Antonio	Texas
United States	Quality Research, Inc.	San Antonio	Texas
United States	Sun Research Institute	San Antonio	Texas
United States	Covenant Metabolic Specialists - Sarasota	Sarasota	Florida
United States	Liver Institute NW	Seattle	Washington
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Florida Health Sciences Center/Tampa General Hospital/USF	Tampa	Florida
United States	Theia Clinical Research LLC	Temple Terrace	Florida
United States	Adobe Clinical Research LLC	Tucson	Arizona
United States	Aizona Liver Health	Tucson	Arizona
United States	Options Health Research	Tulsa	Oklahoma
United States	ClinCloud LLC Melbourn	Viera	Florida
United States	Impact Research Institute	Waco	Texas
United States	Metabolic Research Institute, Inc.	West Palm Beach	Florida
United States	Clinical Research Institute of Ohio	Westlake	Ohio
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
HighTide Biopharma Pty Ltd

Countries where clinical trial is conducted

United States,  China,  Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Endpoint	A decrease of =2-points in non-alcoholic fatty liver disease activity score (NAS) with =1-point decrease of either lobular inflammation or ballooning and no worsening of fibrosis; OR Resolution of non-alcoholic steatohepatitis (NASH) (defined as the overall histopathologic interpretation of 1) "no fatty liver disease" or 2) "fatty liver disease (simple or isolated steatosis) without steatohepatitis AND a non-alcoholic fatty liver disease activity score (NAS) of 0 for ballooning and 0-1 for inflammation and no worsening of fibrosis.; Nonalcoholic fatty liver disease activity score (NAS) is a histological scoring system that assesses a liver biopsy and gives scores for steatosis (0-3), lobular inflammation (0-3), and hepatocyte ballooning (0-2). The higher the score the more severe the disease. The total range for non-alcoholic fatty liver disease activity score (NAS) is between 0 to 8. The lower the score the better the outcome.	Up to 60 Weeks
Secondary	Endpoint 1	Percentage of subjects with resolution of non-alcoholic steatohepatitis (NASH) on overall histopathological reading	Up to 60 Weeks
Secondary	Endpoint 2	Percentage of subjects with resolution of non-alcoholic steatohepatitis hepatitis (NASH) and at least a 2-point improvement in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and no worsening of liver fibrosis	Up to 60 Weeks
Secondary	Endpoint 3	Percentage of subjects with a =1-stage improvement in liver fibrosis.	Up to 60 Weeks
Secondary	Endpoint 4	Percentage of subjects with a =1-stage improvement in liver fibrosis and no worsening of non-alcoholic steatohepatitis (NASH).	Up to 60 Weeks
Secondary	Endpoint 5	Percentage of subjects with a =2-stage improvement in liver fibrosis.	Up to 60 Weeks
Secondary	Endpoint 6	Percentage of subjects with a =2-point improvement in non-alcoholic fatty liver disease activity score (NAS) and no worsening of liver fibrosis.	Up to 60 Weeks
Secondary	Endpoint 7	Percentage of subjects with an improvement in each of the individual non-alcoholic fatty liver disease activity score (NAS) components (ballooning, inflammation, or steatosis).	Up to 60 Weeks
Secondary	Endpoint 8	Percentage of subjects with improvement of non-alcoholic steatohepatitis (NASH) based on overall histopathologic interpretation.	Up to 60 Weeks
Secondary	Endpoint 9	Absolute and percent change in alanine aminotransferase (ALT) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 10	Absolute and percent change in aspartate aminotransferase (AST) from baseline to end of treatment.	Up to 60 Weeks.
Secondary	Endpoint 11	Absolute and percent change in gamma-glutamyl transferase (GGT) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 12	Absolute and percent change in total bilirubin from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 13	Absolute and percent change in direct bilirubin from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 14	Absolute and percent change in hemoglobin A1c (HbA1c) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 15	Absolute and percent change in fasting plasma glucose from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 16	Absolute and percent change in body weight from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 17	Absolute and percent change in body mass index (BMI) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 18	Absolute and percent change in hip circumference from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 19	Absolute and percent change in waist circumference from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 20	Absolute and percent change in total cholesterol from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 21	Absolute and percent change in low-density lipoprotein cholesterol (LDL-c) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 22	Absolute and percent change in lipoprotein A (Lpa) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 23	Absolute and percent change in high-density lipoprotein cholesterol (HDL-c) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 24	Absolute and percent change in triglycerides from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 25	Absolute and percent change in apolipoprotein B (ApoB) from baseline to end of treatment.	Up to 60 Weeks
Secondary	Endpoint 26	Absolute and percent change in liver stiffness as measured by vibration-controlled transient elastography (VCTE) using FibroScan® device from baseline to end of treatment.; The VCTE score is measured in Kilopascal Pressure Unit (kPa) and ranges from 2 to 75 kPa. The higher the kPa score the more severe the liver stiffness.	Up to 60 Weeks
Secondary	Endpoint 27	Absolute and percent change in liver fat content as measured by controlled attenuation parameter (CAP) using FibroScan® device from baseline to end of treatment.; The controlled attenuation parameter (CAP) score is measured in decibels per meter (dB/m) it ranges from 100 to 400 dB/m. The higher the controlled attenuation parameter (CAP) score the more severe the steatosis.	Up to 60 Weeks
Secondary	Endpoint 28	Absolute and percent change in the FibroScan-AST (FAST) score from baseline to end of treatment.; Fast score will be calculated based on LSM, CAP and AST values using FAST equation. An equal to or more than 0.35 value thru equal or less than 0.81 value is positive predictive value for nonalcoholic steatohepatitis and a negative predictive value from 0.73 to 1.0.	Up to 60 Weeks