A Phase 2 interventional study of HTD1801 and Placebo in Fatty Liver, Nonalcoholic, NAFLD and Nonalcoholic Fatty Liver Disease, sponsored by HighTide Therapeutics (Hong Kong) Limited. Completed at 17 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by HighTide Therapeutics (Hong Kong) Limited · Phase 2, Interventional, and Treatment
Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.
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.
1,617 studies on the registry are indexed under Non-alcoholic Fatty Liver Disease; 324 are open to participants now.
This study's enrollment of 101 is above the median of 60 across 1,176 interventional studies indexed under Non-alcoholic Fatty Liver Disease.
Browse Non-alcoholic Fatty Liver Disease studies →HighTide Therapeutics (Hong Kong) Limited is the lead sponsor of 8 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: HTD1801
Drug: HTD1801
Drug: Placebo
HTD1801 tablets, 250mg
tablets manufactured to mimic HTD1801 tablets
Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF
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
Change in Fasting Glucose
Change in fasting glucose from Baseline to Week 18 .
Time frame: Baseline through study Week 18
Changes in Hemoglobin A1c
Changes in HbA1c from Baseline to Week 18.
Time frame: Baseline through study week 18
Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF
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
Relative Change in LFC as Measured by MRI-PDFF
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
Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF
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
Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF
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
Change in HOMA-IR
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
Change in LDL-c
Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.
Time frame: Baseline visit through study week 18
Change in Serum Triglycerides
Change in serum triglycerides from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in HDL-c
Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in AST
Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in ALT
Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.
Time frame: Baseline through study week 18
Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18
Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.
Time frame: Baseline through study week 18
Change in Pro-Peptide of Type III Collagen (Pro-C3)
Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.
Time frame: Baseline through study week 18
Change in ELF Score
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
Change in TIMP-1
Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in PIIINP
Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in HA
Change in hyaluronic acid (HA) from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in Total Bile Acids
Changes in total bile acids from Baseline to Week 18.
Time frame: Baseline through study week 18
Change in FGF19
Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18
Time frame: Baseline through study week 18
Number of Participants Reporting an Adverse Events From Baseline Through Week 18
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.
| Milestone | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Started | 34 | 34 | 33 |
| Completed | 29 | 27 | 32 |
| Not completed | 5 | 7 | 1 |
| Withdrew: Adverse event | 1 | 4 | 1 |
| Withdrew: Protocol violation | 1 | 0 | 0 |
| Withdrew: Lost to follow-up | 2 | 2 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 |
| Withdrew: Randomized in error. did not start investigational product. considered an et. | 1 | 0 | 0 |
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.
| Change in percentage of liver fat | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF | -2.918 ± 4.0204 | -4.829 ± 4.3516 | -1.962 ± 4.8844 |
Change in fasting glucose from Baseline to Week 18 .
| mg/dL | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in Fasting Glucose | 120 ± 28.6 | 129 ± 42.5 | 131 ± 40.9 |
Changes in HbA1c from Baseline to Week 18.
| Percentage | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Changes in Hemoglobin A1c | -0.3 ± 0.68 | -0.6 ± 0.96 | 0.1 ± 0.82 |
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.
| Participants | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF | 6 | 10 | 7 |
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.
| Percentage change | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Relative Change in LFC as Measured by MRI-PDFF | -15.097 ± 22.7749 | -24.140 ± 21.7020 | -8.322 ± 24.4804 |
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.
| Participants | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Number of Subjects Who Normalized LFC to <5% as Measured by MRI-PDFF | 1 | 0 | 0 |
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.
| Participants | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Number of Subjects Who Achieved ≥5% Absolute Reduction in Liver Fat Content (LFC) as Measured by MRI-PDFF | 10 | 12 | 8 |
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.
| score on a scale | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in HOMA-IR | -3.38 ± 6.779 | -4.21 ± 7.074 | -6.66 ± 17.752 |
Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.
| mg/dL | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in LDL-c | 5 ± 34.1 | -16 ± 26.5 | 0 ± 20.5 |
Change in serum triglycerides from Baseline to Week 18.
| mg/dL | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in Serum Triglycerides | -41 ± 136.3 | -24 ± 70.4 | 18 ± 142.9 |
Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.
| mg/dL | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in HDL-c | 1 ± 5.7 | 0 ± 8.2 | 0 ± 7.5 |
Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.
| U/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in AST | 0 ± 13.2 | -13 ± 26.3 | -3 ± 11.6 |
Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.
| U/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in ALT | -4 ± 17.9 | -19 ± 27.2 | -3 ± 19.2 |
Proportion of subjects with elevated alanine aminotransferase (ALT) at Baseline who normalized ALT at Week 18.
| Participants | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Proportion of Subjects With Elevated ALT at Baseline Who Normalized ALT at Week 18 | 3 | 9 | 5 |
Change in Pro-C3 from Baseline to Week 18 for subjects with elevated Pro-C3 at Baseline.
| ng/mL | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in Pro-Peptide of Type III Collagen (Pro-C3) | 0.5 ± 5.17 | -2.3 ± 7.09 | -0.8 ± 2.94 |
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.
| score on a scale | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in ELF Score | 0.05 ± 0.723 | -0.10 ± 0.592 | -0.05 ± 0.461 |
Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.
| µg/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in TIMP-1 | 1.8 ± 53.26 | -8.9 ± 57.32 | -6.0 ± 31.55 |
Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.
| µg/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in PIIINP | 0.68 ± 2.905 | 0.03 ± 3.360 | -0.31 ± 2.016 |
Change in hyaluronic acid (HA) from Baseline to Week 18.
| µg/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in HA | -0.64 ± 35.398 | -5.25 ± 34.046 | -3.83 ± 49.844 |
Changes in total bile acids from Baseline to Week 18.
| μmol/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in Total Bile Acids | 1307 ± 1432.6 | 1625 ± 2332.2 | -581 ± 1487.4 |
Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18
| μmol/L | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Change in FGF19 | -11 ± 111.8 | -9 ± 71.1 | -40 ± 84.8 |
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.
| Participants | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Number of Participants Reporting an Adverse Events From Baseline Through Week 18 | 21 | 26 | 20 |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 500mg HTD1801, Bid | 0/33 (0%) | 1/33 (3%) | 21/33 (63.6%) |
| 1000mg HTD1801, Bid | 0/34 (0%) | 1/34 (2.9%) | 26/34 (76.5%) |
| Placebo, Bid | 0/33 (0%) | 1/33 (3%) | 20/33 (60.6%) |
| Event | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Myocardial infarctionCardiac disorders | 1/33 | 1/34 | 0/33 |
| Bladder transitional cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/33 | 0/34 | 1/33 |
| Decreased oxygen saturationRespiratory, thoracic and mediastinal disorders | 0/33 | 1/34 | 0/33 |
| Event | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid |
|---|---|---|---|
| Gastrointestinal DisordersGastrointestinal disorders | 14/33 | 19/34 | 10/33 |
| Infections and InfestationsInfections and infestations | 4/33 | 5/34 | 11/33 |
| Nervous system disordersNervous system disorders | 3/33 | 5/34 | 3/33 |
| Respiratory disordersRespiratory, thoracic and mediastinal disorders | 1/33 | 1/34 | 3/33 |
| General DisordersGeneral disorders | 2/33 | 3/34 | 0/33 |
| Metabolic disordersMetabolism and nutrition disorders | 0/33 | 2/34 | 2/33 |
| InjuryInjury, poisoning and procedural complications | 1/33 | 0/34 | 2/33 |
| Skin disordersSkin and subcutaneous tissue disorders | 1/33 | 2/34 | 1/33 |
| Endocrine DisordersEndocrine disorders | 0/33 | 2/34 | 0/33 |
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(years) | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid | Total |
|---|---|---|---|---|
| Mean | 58 ± 10.2 | 53 ± 12.2 | 58 ± 10.7 | 56 ± 11.2 |
| Sex: Female, Male(Participants) | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid | Total |
|---|---|---|---|---|
| Female | 26 | 24 | 22 | 72 |
| Male | 7 | 10 | 11 | 28 |
| Race (NIH/OMB)(Participants) | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 1 | 1 | 0 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 3 | 2 | 0 | 5 |
| White | 29 | 31 | 31 | 91 |
| More than one race | 0 | 0 | 2 | 2 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| All Randomized Subjects(Participants) | 500mg HTD1801, Bid | 1000mg HTD1801, Bid | Placebo, Bid | Total |
|---|---|---|---|---|
| Disposition | 33 | 34 | 33 | 100 |
| Eligible Subjects | 32 | 33 | 33 | 98 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: Berberine ursodeoxycholate
Non-alcoholic Fatty Liver Disease →
HighTide Therapeutics (Hong Kong) Limited