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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Fatty Liver, Nonalcoholic
NAFLD
Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Digestive System Diseases
Type 2 Diabetes Mellitus (T2DM)
Interventions Drug: HTD1801
Drug: Placebo
Enrollment 101
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description HTD1801: HTD1801 tablets, 250mg HTD1801: HTD1801 tablets, 250mg Placebo: tablets manufactured to mimic HTD1801 tablets
Period Title: Overall Study
Started 34 34 33
Completed 29 27 32
Not Completed 5 7 1
Reason Not Completed
Adverse Event             1             4             1
Protocol Violation             1             0             0
Lost to Follow-up             2             2             0
Withdrawal by Subject             0             1             0
Randomized in error. Did not start investigational product. Considered an ET.             1             0             0
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid Total
Hide Arm/Group Description HTD1801: HTD1801 tablets, 250mg HTD1801: HTD1801 tablets, 250mg Placebo: tablets manufactured to mimic HTD1801 tablets Total of all reporting groups
Overall Number of Baseline Participants 33 34 33 100
Hide Baseline Analysis Population Description
One-hundred one subjects were randomized into the study, however, subject did not receive investigational study drug and was not included in the efficacy or safety analyses data sets.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 34 participants 33 participants 100 participants
58  (10.2) 53  (12.2) 58  (10.7) 56  (11.2)
[1]
Measure Analysis Population Description: One subject was randomized in error and did not receive investigational study drug.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 33 participants 100 participants
Female
26
  78.8%
24
  70.6%
22
  66.7%
72
  72.0%
Male
7
  21.2%
10
  29.4%
11
  33.3%
28
  28.0%
[1]
Measure Analysis Population Description: One subject randomized in error and did not receive investigational study medication.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 33 participants 100 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   3.0%
1
   2.9%
0
   0.0%
2
   2.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   9.1%
2
   5.9%
0
   0.0%
5
   5.0%
White
29
  87.9%
31
  91.2%
31
  93.9%
91
  91.0%
More than one race
0
   0.0%
0
   0.0%
2
   6.1%
2
   2.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: One subject randomized in error and did not receive investigational study drug.
All Randomized Subjects   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 34 participants 33 participants 100 participants
Disposition
33
 100.0%
34
 100.0%
33
 100.0%
100
 100.0%
Eligible Subjects
32
  97.0%
33
  97.1%
33
 100.0%
98
  98.0%
[1]
Measure Description: Results are reported for all subjects who signed the Institutional Review Board (IRB) approved informed consent form and were randomized into the study. One subject was randomized in error but did not receive investigational study drug and was not included in the analyses efficacy and safety datasets.
1.Primary Outcome
Title Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF
Hide Description 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.
Time Frame Baseline through study Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 30 27 32
Mean (Standard Deviation)
Unit of Measure: Change in percentage of liver fat
-2.918  (4.0204) -4.829  (4.3516) -1.962  (4.8844)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Change in Fasting Glucose
Hide Description Change in fasting glucose from Baseline to Week 18 .
Time Frame Baseline through study Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in glucose endpoint.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: mg/dL
120  (28.6) 129  (42.5) 131  (40.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.152
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Changes in Hemoglobin A1c
Hide Description Changes in HbA1c from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for change in hemoglobin A1c endpoint..
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: Percentage
-0.3  (0.68) -0.6  (0.96) 0.1  (0.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF
Hide Description 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.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 30 27 32
Measure Type: Count of Participants
Unit of Measure: Participants
6
  20.0%
10
  37.0%
7
  21.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.884
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.236
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
5.Secondary Outcome
Title Relative Change in LFC as Measured by MRI-PDFF
Hide Description 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.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 30 27 32
Mean (Standard Deviation)
Unit of Measure: Percentage change
-15.097  (22.7749) -24.140  (21.7020) -8.322  (24.4804)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.196
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
6.Secondary Outcome
Title Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF
Hide Description 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.
Time Frame Baseline through study Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 30 27 32
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.3%
0
   0.0%
0
   0.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.294
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF
Hide Description 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.
Time Frame Baseline through study Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy set which included all subjects who completed at least 80 days of study drug and had a Week 18 or Early Termination (ET) visit MRI-PDFF assessment.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 30 27 32
Measure Type: Count of Participants
Unit of Measure: Participants
10
  33.3%
12
  44.4%
8
  25.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.287
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
8.Secondary Outcome
Title Change in HOMA-IR
Hide Description 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.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the changes in HOMA-IR endpoint and included 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: score on a scale
-3.38  (6.779) -4.21  (7.074) -6.66  (17.752)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.201
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.534
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
9.Secondary Outcome
Title Change in LDL-c
Hide Description Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.
Time Frame Baseline visit through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the changes in LDL-c endpoint and included 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 27 25 29
Mean (Standard Deviation)
Unit of Measure: mg/dL
5  (34.1) -16  (26.5) 0  (20.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.955
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
10.Secondary Outcome
Title Change in Serum Triglycerides
Hide Description Change in serum triglycerides from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited subjects with data was available for the changes in serum triglycerides endpoint and included 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: mg/dL
-41  (136.3) -24  (70.4) 18  (142.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.120
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
11.Secondary Outcome
Title Change in HDL-c
Hide Description Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the change in HDL-c endpoint and included 4 more subjects than were in the Efficacy set..
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: mg/dL
1  (5.7) 0  (8.2) 0  (7.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.955
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Change in AST
Hide Description Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures included subjects with data was available for the change in AST endpoint and included 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: U/L
0  (13.2) -13  (26.3) -3  (11.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.488
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title Change in ALT
Hide Description Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the absolute change in alanine aminotransferase endpoint and had 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: U/L
-4  (17.9) -19  (27.2) -3  (19.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.674
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18
Hide Description Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with elevated alanine aminotransferase (ALT) at Baseline
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 14 18 20
Measure Type: Count of Participants
Unit of Measure: Participants
3
  21.4%
9
  50.0%
5
  25.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.588
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.103
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
15.Secondary Outcome
Title Change in Pro-Peptide of Type III Collagen (Pro-C3)
Hide Description Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data was available for the change in Pro-C3 endpoint and included 4 more subjects than were in the Efficacy set...
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.5  (5.17) -2.3  (7.09) -0.8  (2.94)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.236
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.944
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
16.Secondary Outcome
Title Change in ELF Score
Hide Description 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.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in ELF score endpoint and include 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 25 32
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.05  (0.723) -0.10  (0.592) -0.05  (0.461)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.267
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.911
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
17.Secondary Outcome
Title Change in TIMP-1
Hide Description Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in TIMP-1 endpoint and include 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 26 32
Mean (Standard Deviation)
Unit of Measure: µg/L
1.8  (53.26) -8.9  (57.32) -6.0  (31.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.387
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.855
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
18.Secondary Outcome
Title Change in PIIINP
Hide Description Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in PIIINP and included 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 25 32
Mean (Standard Deviation)
Unit of Measure: µg/L
0.68  (2.905) 0.03  (3.360) -0.31  (2.016)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.107
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.489
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
19.Secondary Outcome
Title Change in HA
Hide Description Change in hyaluronic acid (HA) from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in HA and included set had 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 29 25 32
Mean (Standard Deviation)
Unit of Measure: µg/L
-0.64  (35.398) -5.25  (34.046) -3.83  (49.844)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.515
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.887
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
20.Secondary Outcome
Title Change in Total Bile Acids
Hide Description Changes in total bile acids from Baseline to Week 18.
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in total bile acids and included for 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 11 12 13
Mean (Standard Deviation)
Unit of Measure: μmol/L
1307  (1432.6) 1625  (2332.2) -581  (1487.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
21.Secondary Outcome
Title Change in FGF19
Hide Description Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18
Time Frame Baseline through study week 18
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Efficacy set was utilized for analyses of secondary endpoints, as well as select analyses of LFC. This analysis set included all randomized subjects who received at least one dose of study drug and who had at least one post-dose MRI-PDFF assessment. The summary measures are additionally limited to those subjects with data available for the change in FGF-19 and include 4 more subjects than were in the Efficacy set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 11 12 13
Mean (Standard Deviation)
Unit of Measure: μmol/L
-11  (111.8) -9  (71.1) -40  (84.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 500mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1000mg HTD1801, Bid, Placebo, Bid
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.171
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
22.Secondary Outcome
Title Number of Participants Reporting an Adverse Events From Baseline Through Week 18
Hide Description 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.
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.
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Hide Analysis Population Description
All subjects included in the safety set.
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description:
HTD1801: HTD1801 tablets, 250mg
HTD1801: HTD1801 tablets, 250mg
Placebo: tablets manufactured to mimic HTD1801 tablets
Overall Number of Participants Analyzed 33 34 33
Measure Type: Count of Participants
Unit of Measure: Participants
21
  63.6%
26
  76.5%
20
  60.6%
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 for a completed subject.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Hide Arm/Group Description HTD1801: HTD1801 tablets, 250mg HTD1801: HTD1801 tablets, 250mg Placebo: tablets manufactured to mimic HTD1801 tablets
All-Cause Mortality
500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/33 (0.00%)      0/34 (0.00%)      0/33 (0.00%)    
Hide Serious Adverse Events
500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/33 (3.03%)      1/34 (2.94%)      1/33 (3.03%)    
Cardiac disorders       
Myocardial infarction  1 [1]  1/33 (3.03%)  1 1/34 (2.94%)  1 0/33 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder transitional cell carcinoma  1 [2]  0/33 (0.00%)  0 0/34 (0.00%)  0 1/33 (3.03%)  1
Respiratory, thoracic and mediastinal disorders       
Decreased oxygen saturation  1 [3]  0/33 (0.00%)  0 1/34 (2.94%)  1 0/33 (0.00%)  0
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
[1]
SAE of MI occurred on Study Day 112 and resolved same day. Presented to emergency with complaint of sharp substernal chest pain. Had severe distal RCA/r PDA disease. Successful per cutaneous intervention performed. Study drug discont. Unrelated.
[2]
Bladder transitional cell carcinoma requiring hospitalization. after presenting to hospital on Study Day 116 with hematuria. Resolved Study Day 117. Unrelated.
[3]
Subject was admitted to hospital for elective surgery (left shoulder arthroscopic surgery). Postoperatively, subject developed hypoxia and was placed on oxygen. Hospitalization was prolonged.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
500mg HTD1801, Bid 1000mg HTD1801, Bid Placebo, Bid
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/33 (63.64%)      26/34 (76.47%)      20/33 (60.61%)    
Endocrine disorders       
Endocrine Disorders  1 [1]  0/33 (0.00%)  0 2/34 (5.88%)  2 0/33 (0.00%)  0
Gastrointestinal disorders       
Gastrointestinal Disorders  1 [2]  14/33 (42.42%)  27 19/34 (55.88%)  40 10/33 (30.30%)  19
General disorders       
General Disorders  1 [3]  2/33 (6.06%)  5 3/34 (8.82%)  4 0/33 (0.00%)  0
Infections and infestations       
Infections and Infestations  1 [4]  4/33 (12.12%)  4 5/34 (14.71%)  5 11/33 (33.33%)  18
Injury, poisoning and procedural complications       
Injury  1 [5]  1/33 (3.03%)  1 0/34 (0.00%)  0 2/33 (6.06%)  2
Metabolism and nutrition disorders       
Metabolic disorders  1 [6]  0/33 (0.00%)  0 2/34 (5.88%)  4 2/33 (6.06%)  3
Nervous system disorders       
Nervous system disorders  1 [7]  3/33 (9.09%)  3 5/34 (14.71%)  6 3/33 (9.09%)  4
Respiratory, thoracic and mediastinal disorders       
Respiratory disorders  1 [8]  1/33 (3.03%)  2 1/34 (2.94%)  2 3/33 (9.09%)  6
Skin and subcutaneous tissue disorders       
Skin disorders  1 [9]  1/33 (3.03%)  2 2/34 (5.88%)  3 1/33 (3.03%)  1
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
[1]
Hypothyroidism,
[2]
Diarrhea, nausea, abdominal pain upper, abdominal pain, constipation, flatulence, gastroesophageal reflux disease,
[3]
Fatigue, investigations (alanine aminotransferase increased, blood glucose decreased)
[4]
Upper respiratory tract infection, Nasopharyngitis, bronchitis, gastroenteritis viral,
[5]
Corneal abrasion, heat exhaustion, joint injury
[6]
Decreased appetite, dehydration, diabetes mellitus inadequate control, hypertriglyceridemia
[7]
Headache
[8]
Cough, nasal congestion, sinus congestion
[9]
Rash, alopecia
The study was conducted exclusively in the United States and data may not be applicable to other populations. The study enrolled subjects with presumed NASH and diabetes. Further studies to determine the effect of HTD1801 in non-diabetics may be needed. Future studies will focus on patients with biopsy confirmed NASH and use liver histology (i.e., liver biopsies) as a histological endpoint.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: HighTide Therapeutics
Phone: 314-791-0593
EMail: adibisceglie@hightidetx.com
Layout table for additonal information
Responsible Party: HighTide Biopharma Pty Ltd
ClinicalTrials.gov Identifier: NCT03656744    
Other Study ID Numbers: HTD1801.PCT012
First Submitted: August 30, 2018
First Posted: September 4, 2018
Results First Submitted: May 12, 2021
Results First Posted: December 29, 2021
Last Update Posted: December 29, 2021