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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: HTD1801; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Chinese University of Hong Kong Prince of Wales Hospital
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • FDI Clinical Research
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health (Arizona Liver Health)
    • Peoria, Arizona, United States, 85381
      • Arizona Liver Health - Glendae
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research LLC
    • Tucson, Arizona, United States, 85712
      • Aizona Liver Health
  • California
    • Canoga Park, California, United States, 91302
      • San Fernando Valley Health Institute
    • Garden Grove, California, United States, 92845
      • Clinnova Research Solutions
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • Pasadena, California, United States, 91105
      • California Liver Institute
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research, Inc.
    • Fort Myers, Florida, United States, 33912
      • Covenant Metabolic Specialists - Fort Meyers
    • Hialeah Gardens, Florida, United States, 33016
      • Evolution Clinical Trials, Inc.
    • Maitland, Florida, United States, 32751
      • ClinCloud LLC Maitland
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Miami Lakes, Florida, United States, 33016
      • Floridain Clinical Research
    • Sarasota, Florida, United States, 34240
      • Covenant Metabolic Specialists - Sarasota
    • Temple Terrace, Florida, United States, 34211
      • Theia Clinical Research LLC
    • Viera, Florida, United States, 32940
      • ClinCloud LLC Melbourn
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
    • Winter Park, Florida, United States, 32789
      • Conquest Research
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Louisvill Metabolic and Atherosclerosis Research Center (L-MARC)
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Jubilee Clinical Research, Inc.
  • New York
    • New York, New York, United States, 10033
      • Tandem Clinical Research GI - New York
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research - Diabetes and Endocrinology
  • Ohio
    • Westlake, Ohio, United States, 44145
      • Clinical Research Institute of Ohio
  • South Carolina
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch LLC
    • Clarksville, Tennessee, United States, 37043
      • Premier Research
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Austin, Texas, United States, 78757
      • Pinnacle Clinical Research
    • Brownsville, Texas, United States, 78539
      • South Texas Research Institute
    • DeSoto, Texas, United States, 75154
      • Epic Medical Research
    • Georgetown, Texas, United States, 78229
      • Pinnacle Research, Georgetown TX
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • San Antonio, Texas, United States, 78209
      • Quality Research, Inc.
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research San Antonio
    • Waco, Texas, United States, 76710
      • Impact Research Institute
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute NW

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HTD1801; HTD1801,1250 mg, BID	Drug: HTD1801; HTD1801,1250 mg, BID; Other Names: HTD1801 capsules
Placebo Comparator: placebo; placebo, BID	Drug: Placebo; Placebo, BID; Other Names: placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endpoint 1	Percentage of subjects with resolution of non-alcoholic steatohepatitis (NASH) on overall histopathological reading	Up to 60 Weeks
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
Endpoint 3	Percentage of subjects with a ≥1-stage improvement in liver fibrosis.	Up to 60 Weeks
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
Endpoint 5	Percentage of subjects with a ≥2-stage improvement in liver fibrosis.	Up to 60 Weeks
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
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
Endpoint 8	Percentage of subjects with improvement of non-alcoholic steatohepatitis (NASH) based on overall histopathologic interpretation.	Up to 60 Weeks
Endpoint 9	Absolute and percent change in alanine aminotransferase (ALT) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 10	Absolute and percent change in aspartate aminotransferase (AST) from baseline to end of treatment.	Up to 60 Weeks.
Endpoint 11	Absolute and percent change in gamma-glutamyl transferase (GGT) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 12	Absolute and percent change in total bilirubin from baseline to end of treatment.	Up to 60 Weeks
Endpoint 13	Absolute and percent change in direct bilirubin from baseline to end of treatment.	Up to 60 Weeks
Endpoint 14	Absolute and percent change in hemoglobin A1c (HbA1c) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 15	Absolute and percent change in fasting plasma glucose from baseline to end of treatment.	Up to 60 Weeks
Endpoint 16	Absolute and percent change in body weight from baseline to end of treatment.	Up to 60 Weeks
Endpoint 17	Absolute and percent change in body mass index (BMI) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 18	Absolute and percent change in hip circumference from baseline to end of treatment.	Up to 60 Weeks
Endpoint 19	Absolute and percent change in waist circumference from baseline to end of treatment.	Up to 60 Weeks
Endpoint 20	Absolute and percent change in total cholesterol from baseline to end of treatment.	Up to 60 Weeks
Endpoint 21	Absolute and percent change in low-density lipoprotein cholesterol (LDL-c) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 22	Absolute and percent change in lipoprotein A (Lpa) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 23	Absolute and percent change in high-density lipoprotein cholesterol (HDL-c) from baseline to end of treatment.	Up to 60 Weeks
Endpoint 24	Absolute and percent change in triglycerides from baseline to end of treatment.	Up to 60 Weeks
Endpoint 25	Absolute and percent change in apolipoprotein B (ApoB) from baseline to end of treatment.	Up to 60 Weeks
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
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
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

Collaborators and Investigators

• Sponsor: HighTide Biopharma Pty Ltd
• Investigators: Study Director: Adrian Di Bisceglie, MD, FACP, FAASLD, HighTide Therapeutics USA, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2022
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: November 11, 2022
• First Posted (Actual): November 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Metabolic Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Liver Diseases; Fibrosis; Diabetes Mellitus, Type 2; Diabetes Mellitus; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Prediabetic State
• Other Study ID Numbers: HTD1801.PCT014; The CENTRICITY Study (Other Identifier: HighTide Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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