We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03656744
Recruitment Status : Completed
First Posted : September 4, 2018
Results First Posted : December 29, 2021
Last Update Posted : December 29, 2021
Sponsor:
Information provided by (Responsible Party):
HighTide Biopharma Pty Ltd

Brief Summary:
Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.

Condition or disease Intervention/treatment Phase
Fatty Liver, Nonalcoholic NAFLD Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Digestive System Diseases Type 2 Diabetes Mellitus (T2DM) Drug: HTD1801 Drug: Placebo Phase 2

Detailed Description:

This 18-week randomized, double-blind, parallel-group, proof of concept (POC), dose-ranging study compared multiple doses of HTD1801 to placebo in a 1:1:1 ratio. Since accumulation of hepatic fat is considered the "first hit" in the pathogenesis of NASH (Adams and Angulo 2006), change in liver fat content (LFC) by magnetic resonance imaging estimated proton density fat fraction (MRI-PDFF) is an appropriate primary endpoint and is consistent with that used in other recent Phase 2 POC studies in NASH (Harrison et al., 2018, Madrigal Pharmaceuticals 2018).

The Harrison et al., 2018, Madrigal Pharmaceuticals 2018 study showed clinically meaningful absolute and relative reductions in LFC assessed by MRI-PDFF over 12-week treatment periods thus, it was considered that an 18 week HTD1801 treatment period would therefore be adequate to assess the study's primary endpoint and to maximize collection of exposure and safety related data.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM
Actual Study Start Date : November 26, 2018
Actual Primary Completion Date : February 7, 2020
Actual Study Completion Date : March 9, 2020


Arm Intervention/treatment
Experimental: 500mg HTD1801, bid Drug: HTD1801
HTD1801 tablets, 250mg

Experimental: 1000mg HTD1801, bid Drug: HTD1801
HTD1801 tablets, 250mg

Placebo Comparator: placebo, bid Drug: Placebo
tablets manufactured to mimic HTD1801 tablets




Primary Outcome Measures :
  1. Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF [ Time Frame: Baseline through study Week 18 ]
    The primary endpoint was the absolute change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.


Secondary Outcome Measures :
  1. Change in Fasting Glucose [ Time Frame: Baseline through study Week 18 ]
    Change in fasting glucose from Baseline to Week 18 .

  2. Changes in Hemoglobin A1c [ Time Frame: Baseline through study week 18 ]
    Changes in HbA1c from Baseline to Week 18.

  3. Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF [ Time Frame: Baseline through study week 18 ]
    Proportion of subjects who achieved ≥ 30% relative reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

  4. Relative Change in LFC as Measured by MRI-PDFF [ Time Frame: Baseline through study week 18 ]
    Relative change in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

  5. Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF [ Time Frame: Baseline through study Week 18 ]
    Number of subjects who normalized liver fat content (LFC) to <5% as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) at Week 18.

  6. Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF [ Time Frame: Baseline through study Week 18 ]
    Number of subjects who achieved ≥5% absolute reduction in liver fat content (LFC) as measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) from Baseline to Week 18.

  7. Change in HOMA-IR [ Time Frame: Baseline through study week 18 ]
    Change in homeostasis model assessment-estimated insulin resistance (HOMA-IR) from Baseline to Week 18. The higher the HOMA-IR score, the more insulin resistant a person is. Values of <1 are considered optimal while values >2.9 indicate significant insulin resistance.

  8. Change in LDL-c [ Time Frame: Baseline visit through study week 18 ]
    Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.

  9. Change in Serum Triglycerides [ Time Frame: Baseline through study week 18 ]
    Change in serum triglycerides from Baseline to Week 18.

  10. Change in HDL-c [ Time Frame: Baseline through study week 18 ]
    Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.

  11. Change in AST [ Time Frame: Baseline through study week 18 ]
    Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.

  12. Change in ALT [ Time Frame: Baseline through study week 18 ]
    Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.

  13. Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18 [ Time Frame: Baseline through study week 18 ]
    Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.

  14. Change in Pro-Peptide of Type III Collagen (Pro-C3) [ Time Frame: Baseline through study week 18 ]
    Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.

  15. Change in ELF Score [ Time Frame: Baseline through study week 18 ]
    Change in the enhanced liver fibrosis (ELF) score. The ELF score is calculated using a published algorithm combining the values of a set of extracellular matrix markers, including TIMP-1, PIIINP, and HA. The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. The ELF score is hence used as a prognostic marker for disease progression: ELF score < 9.8 : Low risk of progression, ELF score 9.8 to < 11.3 : Moderate risk of progression and ELF score > = 11.3 : High risk of progression.

  16. Change in TIMP-1 [ Time Frame: Baseline through study week 18 ]
    Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.

  17. Change in PIIINP [ Time Frame: Baseline through study week 18 ]
    Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.

  18. Change in HA [ Time Frame: Baseline through study week 18 ]
    Change in hyaluronic acid (HA) from Baseline to Week 18.

  19. Change in Total Bile Acids [ Time Frame: Baseline through study week 18 ]
    Changes in total bile acids from Baseline to Week 18.

  20. Change in FGF19 [ Time Frame: Baseline through study week 18 ]
    Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18

  21. Number of Participants Reporting an Adverse Events From Baseline Through Week 18 [ Time Frame: Adverse events were collected from the time the subject signed the informed consent form through the date of the last visit for a specific subject, that is, approximately 24 weeks in total for a completed subject. ]
    AEs were mapped to MedDRA version 20.1 preferred term (PT) and system organ class (SOC). If the subject experienced multiple events that mapped to a single preferred term, the greatest severity grade according to CTCAE Version 4.0, and strongest investigator assessment of relation to study medication was assigned to the preferred term. If an event had a missing severity or relationship, it was classified as having the highest severity and/or strongest relationship to study medication. The occurrence of TEAEs was summarized by treatment group by SOC, PT, and severity. Separate summaries of treatment-emergent serious adverse events (SAEs), TEAEs related to study drug, severe or life threatening TEAEs, and TEAEs leading to the discontinuation of study treatment were generated. Additionally, the occurrence of liver-specific AEs was summarized by treatment group. All reported adverse events were listed for individual subjects showing verbatim term, PT and SOC.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of NASH as assessed by MRI
  • Clinically documented diagnosis of T2DM
  • Body mass index (BMI) >25 kg/m2

Exclusion Criteria:

  • Liver disease unrelated to NASH
  • Poorly controlled T2DM or Type 1 Diabetes Mellitus
  • History of alcohol or substance abuse or dependence
  • Inability to undergo MRI for any reason
  • History of significant cardiovascular disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03656744


Locations
Layout table for location information
United States, Arizona
Institute for Liver Health
Chandler, Arizona, United States, 85224
Institute for Liver Health
Tucson, Arizona, United States, 85711
Adobe Clinical Research
Tucson, Arizona, United States, 85712
United States, California
National Research Institute
Panorama City, California, United States, 91402
United States, Florida
Excel Medical Clinical Trials
Boca Raton, Florida, United States, 33434
Florida Research Institute
Lakewood Ranch, Florida, United States, 34211
Compass Research
Orlando, Florida, United States, 32806
United States, Missouri
Kansas City Research Institute
Kansas City, Missouri, United States, 64131
United States, North Carolina
Cumberland Research Associates
Fayetteville, North Carolina, United States, 28304
United States, Tennessee
Gastro One
Germantown, Tennessee, United States, 38138
Digestive Health Research
Hermitage, Tennessee, United States, 37076
United States, Texas
Pinnacle Clinical Research
Austin, Texas, United States, 78746
Doctors Hospital at Renaissance
Edinburg, Texas, United States, 78539
Pinnacle Clinical Research
San Antonio, Texas, United States, 78229
Texas Digestive Disease Consultants
Southlake, Texas, United States, 76092
United States, Washington
Harborview Medical Center
Seattle, Washington, United States, 98195
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
HighTide Biopharma Pty Ltd
Investigators
Layout table for investigator information
Study Director: Adrian Di Bisceglie, MD,FACP,FAASLD HighTide Therapeutics USA, LLC
  Study Documents (Full-Text)

Documents provided by HighTide Biopharma Pty Ltd:
Study Protocol  [PDF] March 27, 2019
Statistical Analysis Plan  [PDF] March 25, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: HighTide Biopharma Pty Ltd
ClinicalTrials.gov Identifier: NCT03656744    
Other Study ID Numbers: HTD1801.PCT012
First Posted: September 4, 2018    Key Record Dates
Results First Posted: December 29, 2021
Last Update Posted: December 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Gastrointestinal Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases