Fatty Liver, NonalcoholicPhase 2NCT03656744
A Study of HTD1801 in Adults With Nonalcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)
A Phase 2 study testing HTD1801 in people with Fatty Liver, Nonalcoholic and NAFLD, run by HighTide Therapeutics (Hong Kong) Limited at 17 sites in United States.
Trial summary
Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Fatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease
- What is being tested?
- HTD1801
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 17 sitesUnited States
- Study dates
- 26 Nov 2018to 9 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of NASH as assessed by MRI
- Clinically documented diagnosis of T2DM
- Body mass index (BMI) >25 kg/m2
Who cannot join
- 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
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Pinnacle Clinical Research
Austin, Texas, 78746
Excel Medical Clinical Trials
Boca Raton, Florida, 33434
Institute for Liver Health
Chandler, Arizona, 85224
Doctors Hospital at Renaissance
Edinburg, Texas, 78539
Cumberland Research Associates
Fayetteville, North Carolina, 28304
Gastro One
Germantown, Tennessee, 38138
Digestive Health Research
Hermitage, Tennessee, 37076
Kansas City Research Institute
Kansas City, Missouri, 64131
Florida Research Institute
Lakewood Rch, Florida, 34211
Compass Research
Orlando, Florida, 32806
National Research Institute
Panorama City, California, 91402
Pinnacle Clinical Research
San Antonio, Texas, 78229
Harborview Medical Center
Seattle, Washington, 98195
University of Washington Medical Center
Seattle, Washington, 98195
Texas Digestive Disease Consultants
Southlake, Texas, 76092
Institute for Liver Health
Tucson, Arizona, 85711
Adobe Clinical Research
Tucson, Arizona, 85712
About this study
Official title: A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM
Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.
Read the 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.
- Conditions
- Fatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Digestive System Diseases, Type 2 Diabetes Mellitus (T2DM)
- Being tested
- HTD1801, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Digestive System Diseases, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HTD1801Drug
HTD1801 tablets, 250mg
PlaceboDrug
tablets manufactured to mimic HTD1801 tablets
| Study group | Role | What they receive |
|---|---|---|
| 500mg HTD1801, bid | Experimental | Not described Receives: Drug: HTD1801 |
| 1000mg HTD1801, bid | Experimental | Not described Receives: Drug: HTD1801 |
| placebo, bid | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline through study Week 18
Secondary outcomes (21)
Change in Fasting Glucose
Change in fasting glucose from Baseline to Week 18 .
Measured: Baseline through study Week 18
Changes in Hemoglobin A1c
Changes in HbA1c from Baseline to Week 18.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline through study week 18
Change in LDL-c
Change in low-density lipoprotein cholesterol (LDL-c) from Baseline to Week 18.
Measured: Baseline visit through study week 18
Change in Serum Triglycerides
Change in serum triglycerides from Baseline to Week 18.
Measured: Baseline through study week 18
Change in HDL-c
Change in high-density lipoprotein cholesterol (HDL-c) from Baseline to Week 18.
Measured: Baseline through study week 18
Change in AST
Absolute change in aspartate aminotransferase (AST) from Baseline to Week 18.
Measured: Baseline through study week 18
Change in ALT
Absolute change in alanine aminotransferase (ALT) from Baseline to Week 18.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline through study week 18
Change in TIMP-1
Change in tissue inhibitor of metalloproteinases 1 (TIMP-1) from Baseline to Week 18.
Measured: Baseline through study week 18
Change in PIIINP
Change in N-terminal pro-peptide of type III collagen (PIIINP) from Baseline to Week 18.
Measured: Baseline through study week 18
Change in HA
Change in hyaluronic acid (HA) from Baseline to Week 18.
Measured: Baseline through study week 18
Change in Total Bile Acids
Changes in total bile acids from Baseline to Week 18.
Measured: Baseline through study week 18
Change in FGF19
Change in fibroblast growth factor 19 (FGF19) from Baseline to Week 18
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2018
- Study start26 Nov 2018
- Primary completion7 Feb 2020
- Study completion9 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fatty Liver, NonalcoholicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- HighTide Therapeutics (Hong Kong) Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adrian Di Bisceglie, MD,FACP,FAASLD, Study director, HighTide Therapeutics USA, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03656744
- Sponsor's protocol ID
- HTD1801.PCT012
- Status last verified
- Aug 2026
- First submitted
- 30 Aug 2018
- Last updated
- 25 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Harrison SA, Gunn N, Neff GW, Kohli A, Liu L, Flyer A, Goldkind L, Di Bisceglie AM. A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Nat Commun. 2021 Sep 17;12(1):5503. doi: 10.1038/s41467-021-25701-5.
PubMed 34535644
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM
- ClinicalTrials.gov ID
- NCT03656744
- Acronym / sponsor ID
- HTD1801.PCT012
- Conditions
- Fatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Digestive System Diseases, Type 2 Diabetes Mellitus (T2DM)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- HighTide Therapeutics (Hong Kong) LimitedIndustry (pharma, biotech, devices)
- Study start
- 26 Nov 2018 (actual)
- Primary completion
- 7 Feb 2020 (actual)
- Study completion
- 9 Mar 2020 (actual)
- First posted
- 4 Sep 2018 (actual)
- Results
- Posted 29 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized, double-blind, placebo-controlled, parallel-group study comparing multiple doses of HTD1801 to placebo.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 500mg HTD1801, bid | Experimental | Drug: HTD1801 |
| 1000mg HTD1801, bid | Experimental | Drug: HTD1801 |
| placebo, bid | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Clinical diagnosis of NASH as assessed by MRI
- Clinically documented diagnosis of T2DM
- Body mass index (BMI) >25 kg/m2
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HTD1801HTD1801 tablets, 250mg | Drug | 1000mg HTD1801, bid, 500mg HTD1801, bid |
| Placebotablets manufactured to mimic HTD1801 tablets | Drug | placebo, bid |
Primary outcome
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.
21 secondary outcomes
Change in Fasting Glucose
Time frame: Baseline through study Week 18
Changes in Hemoglobin A1c
Time frame: Baseline through study week 18
Proportion of Subjects Who Achieved ≥ 30% Relative Reduction in LFC as Measured by MRI-PDFF
Time frame: Baseline through study week 18
Relative Change in LFC as Measured by MRI-PDFF
Time frame: Baseline through study week 18
Number of Subjects Who Normalized LFC to <5% 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 MRI-PDFF
Time frame: Baseline through study Week 18
Change in HOMA-IR
Time frame: Baseline through study week 18
Change in LDL-c
Time frame: Baseline visit through study week 18
Change in Serum Triglycerides
Time frame: Baseline through study week 18
Change in HDL-c
Time frame: Baseline through study week 18
Change in AST
Time frame: Baseline through study week 18
Change in ALT
Time frame: Baseline through study week 18
Proportion of Subjects With Elevated 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)
Time frame: Baseline through study week 18
Change in ELF Score
Time frame: Baseline through study week 18
Change in TIMP-1
Time frame: Baseline through study week 18
Change in PIIINP
Time frame: Baseline through study week 18
Change in HA
Time frame: Baseline through study week 18
Change in Total Bile Acids
Time frame: Baseline through study week 18
Change in FGF19
Time frame: Baseline through study week 18
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34535644Harrison SA, Gunn N, Neff GW, Kohli A, Liu L, Flyer A, Goldkind L, Di Bisceglie AM. A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Nat Commun. 2021 Sep 17;12(1):5503. doi: 10.1038/s41467-021-25701-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrian Di Bisceglie, MD,FACP,FAASLD study director
HighTide Therapeutics USA, LLC
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HTD1801 in people with Fatty Liver, Nonalcoholic and NAFLD, run by HighTide Therapeutics (Hong Kong) Limited at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change in Liver Fat Content (LFC) as Measured by MRI-PDFF (time frame: Baseline through study Week 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03656744, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.