HTD1801 in Adults With Nonalcoholic Steatohepatitis and Liver Fibrosis Who Have Type 2 Diabetes or Pre-Diabetes
- Conditions
- Nonalcoholic Steatohepatitis (NASH)Type 2 Diabetes
- Interventions
- Drug: Placebo
- Registration Number
- NCT05623189
- Lead Sponsor
- HighTide Biopharma Pty Ltd
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 218
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description HTD1801 HTD1801 HTD1801,1250 mg, BID placebo Placebo placebo, BID
- Primary Outcome Measures
Name Time Method Primary Endpoint Up to 60 Weeks 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.
- Secondary Outcome Measures
Name Time Method Endpoint 5 Up to 60 Weeks Percentage of subjects with a ≥2-stage improvement in liver fibrosis.
Endpoint 6 Up to 60 Weeks Percentage of subjects with a ≥2-point improvement in non-alcoholic fatty liver disease activity score (NAS) and no worsening of liver fibrosis.
Endpoint 1 Up to 60 Weeks Percentage of subjects with resolution of non-alcoholic steatohepatitis (NASH) on overall histopathological reading
Endpoint 2 Up to 60 Weeks 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
Endpoint 4 Up to 60 Weeks Percentage of subjects with a ≥1-stage improvement in liver fibrosis and no worsening of non-alcoholic steatohepatitis (NASH).
Endpoint 3 Up to 60 Weeks Percentage of subjects with a ≥1-stage improvement in liver fibrosis.
Endpoint 7 Up to 60 Weeks Percentage of subjects with an improvement in each of the individual non-alcoholic fatty liver disease activity score (NAS) components (ballooning, inflammation, or steatosis).
Endpoint 8 Up to 60 Weeks Percentage of subjects with improvement of non-alcoholic steatohepatitis (NASH) based on overall histopathologic interpretation.
Endpoint 9 Up to 60 Weeks Absolute and percent change in alanine aminotransferase (ALT) from baseline to end of treatment.
Endpoint 10 Up to 60 Weeks. Absolute and percent change in aspartate aminotransferase (AST) from baseline to end of treatment.
Endpoint 11 Up to 60 Weeks Absolute and percent change in gamma-glutamyl transferase (GGT) from baseline to end of treatment.
Endpoint 12 Up to 60 Weeks Absolute and percent change in total bilirubin from baseline to end of treatment.
Endpoint 13 Up to 60 Weeks Absolute and percent change in direct bilirubin from baseline to end of treatment.
Endpoint 14 Up to 60 Weeks Absolute and percent change in hemoglobin A1c (HbA1c) from baseline to end of treatment.
Endpoint 15 Up to 60 Weeks Absolute and percent change in fasting plasma glucose from baseline to end of treatment.
Endpoint 16 Up to 60 Weeks Absolute and percent change in body weight from baseline to end of treatment.
Endpoint 17 Up to 60 Weeks Absolute and percent change in body mass index (BMI) from baseline to end of treatment.
Endpoint 18 Up to 60 Weeks Absolute and percent change in hip circumference from baseline to end of treatment.
Endpoint 19 Up to 60 Weeks Absolute and percent change in waist circumference from baseline to end of treatment.
Endpoint 20 Up to 60 Weeks Absolute and percent change in total cholesterol from baseline to end of treatment.
Endpoint 21 Up to 60 Weeks Absolute and percent change in low-density lipoprotein cholesterol (LDL-c) from baseline to end of treatment.
Endpoint 22 Up to 60 Weeks Absolute and percent change in lipoprotein A (Lpa) from baseline to end of treatment.
Endpoint 23 Up to 60 Weeks Absolute and percent change in high-density lipoprotein cholesterol (HDL-c) from baseline to end of treatment.
Endpoint 24 Up to 60 Weeks Absolute and percent change in triglycerides from baseline to end of treatment.
Endpoint 25 Up to 60 Weeks Absolute and percent change in apolipoprotein B (ApoB) from baseline to end of treatment.
Endpoint 26 Up to 60 Weeks 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.Endpoint 27 Up to 60 Weeks 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.Endpoint 28 Up to 60 Weeks 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.
Trial Locations
- Locations (45)
Catalina Research Institute
🇺🇸Montclair, California, United States
FDI Clinical Research
🇵🇷San Juan, Puerto Rico
The Institute for Liver Health (Arizona Liver Health)
🇺🇸Chandler, Arizona, United States
Arizona Liver Health - Glendae
🇺🇸Peoria, Arizona, United States
Adobe Clinical Research LLC
🇺🇸Tucson, Arizona, United States
Aizona Liver Health
🇺🇸Tucson, Arizona, United States
San Fernando Valley Health Institute
🇺🇸Canoga Park, California, United States
Clinnova Research Solutions
🇺🇸Garden Grove, California, United States
California Liver Institute
🇺🇸Pasadena, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Excel Medical Clinical Trials, LLC
🇺🇸Boca Raton, Florida, United States
Tampa Bay Medical Research, Inc.
🇺🇸Clearwater, Florida, United States
Covenant Metabolic Specialists - Fort Meyers
🇺🇸Fort Myers, Florida, United States
Evolution Clinical Trials, Inc.
🇺🇸Hialeah Gardens, Florida, United States
ClinCloud LLC Maitland
🇺🇸Maitland, Florida, United States
Panax Clinical Research
🇺🇸Miami Lakes, Florida, United States
Floridain Clinical Research
🇺🇸Miami Lakes, Florida, United States
Clinical Pharmacology of Miami, LLC
🇺🇸Miami, Florida, United States
Tandem Clinical Research GI - New York
🇺🇸New York, New York, United States
Lucas Research - Diabetes and Endocrinology
🇺🇸Morehead City, North Carolina, United States
Covenant Metabolic Specialists - Sarasota
🇺🇸Sarasota, Florida, United States
ClinCloud LLC Melbourn
🇺🇸Viera, Florida, United States
Metabolic Research Institute, Inc.
🇺🇸West Palm Beach, Florida, United States
Conquest Research
🇺🇸Winter Park, Florida, United States
Louisvill Metabolic and Atherosclerosis Research Center (L-MARC)
🇺🇸Louisville, Kentucky, United States
Theia Clinical Research LLC
🇺🇸Temple Terrace, Florida, United States
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Jubilee Clinical Research, Inc.
🇺🇸Las Vegas, Nevada, United States
Clinical Research Institute of Ohio
🇺🇸Westlake, Ohio, United States
Palmetto Clinical Research
🇺🇸Summerville, South Carolina, United States
ClinSearch LLC
🇺🇸Chattanooga, Tennessee, United States
Premier Research
🇺🇸Clarksville, Tennessee, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
Pinnacle Clinical Research
🇺🇸Austin, Texas, United States
South Texas Research Institute
🇺🇸Brownsville, Texas, United States
EPIC Medical Research
🇺🇸DeSoto, Texas, United States
Pinnacle Research, Georgetown TX
🇺🇸Georgetown, Texas, United States
Quality Research, Inc.
🇺🇸San Antonio, Texas, United States
Sun Research Institute
🇺🇸San Antonio, Texas, United States
Pinnacle Clinical Research San Antonio
🇺🇸San Antonio, Texas, United States
Impact Research Institute
🇺🇸Waco, Texas, United States
Manassas Clinical Research Center
🇺🇸Manassas, Virginia, United States
Liver Institute NW
🇺🇸Seattle, Washington, United States
Chinese University of Hong Kong Prince of Wales Hospital
🇭🇰Shatin, Hong Kong