HTD1801 for Non-alcoholic Fatty Liver Disease

(CENTRICITY Trial)

No longer recruiting at 61 trial locations

Overseen By Cathryn Bennett, BN, RN, CCRA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: HighTide Biopharma Pty Ltd

Disqualifiers: Fibrosis stage 4, Alcohol abuse, Cardiovascular disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 60 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests HTD1801 to determine its effectiveness for people with non-alcoholic steatohepatitis (NASH), a type of liver disease, who also have type 2 diabetes or pre-diabetes. The study compares HTD1801 to a placebo (a look-alike pill with no active ingredient) to assess whether HTD1801 can improve liver health. Suitable candidates for this trial have been diagnosed with NASH, show signs of liver fibrosis (scarring), have type 2 diabetes or pre-diabetes, and have a BMI over 25. As a Phase 2 trial, this research measures how well HTD1801 works in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that HTD1801 is likely to be safe for humans?

Research has shown that HTD1801 might be a safe option for individuals with non-alcoholic fatty liver disease. In one study, patients took HTD1801 for 18 weeks and generally tolerated it well, with no reports of serious side effects. Some participants experienced mild side effects, but these were not severe enough to discontinue treatment. This suggests that HTD1801 could be safe and might offer a promising treatment for liver issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-alcoholic fatty liver disease?

Unlike the standard treatments for non-alcoholic fatty liver disease, which often focus on lifestyle changes and medications aimed at managing risk factors like diabetes and high cholesterol, HTD1801 offers a unique approach. HTD1801 is a compound that combines berberine and ursodeoxycholic acid, and it works by targeting liver fat directly, which could help reduce liver inflammation and damage more effectively. Researchers are excited about HTD1801 because it has the potential to address the underlying metabolic issues in the liver rather than just managing symptoms, offering a novel therapeutic strategy for those affected by this condition.

What evidence suggests that HTD1801 might be an effective treatment for non-alcoholic fatty liver disease?

Research has shown that HTD1801, which participants in this trial may receive, can greatly reduce liver fat in people with non-alcoholic fatty liver disease. In an earlier study, patients who took HTD1801 for 18 weeks had significantly less liver fat compared to those who took a placebo, a pill with no active medicine. MRI, a detailed imaging method, measured this reduction. Additionally, HTD1801 has shown potential in improving liver health in patients with metabolic-associated steatohepatitis (MASH). These findings suggest that HTD1801 could help treat liver issues related to type 2 diabetes or pre-diabetes. ^{1 2 3 4 5}

Who Is on the Research Team?

Adrian Di Bisceglie, MD, FACP, FAASLD

Principal Investigator

Hightide Therapeutics USA, LLC

Are You a Good Fit for This Trial?

This trial is for adults with a body mass index (BMI) over 25 (or over 23 if Asian), who have non-alcoholic steatohepatitis (NASH) with liver fibrosis, and type 2 diabetes or pre-diabetes. Participants must have had these conditions diagnosed at least six months prior to the study and cannot have severe heart disease, type 1 diabetes, substance abuse history, other liver diseases, or be unwilling to undergo liver biopsies.

Inclusion Criteria

I have been diagnosed with NASH based on a liver biopsy in the last 6 months.

BMI >25 kilograms/meters squared (>23 kilograms/meters squared if Asian).

I was diagnosed with type 2 diabetes or pre-diabetes at least 6 months ago.

Exclusion Criteria

My condition is at the most advanced stage of scarring of the liver.

I have a history of type 1 diabetes.

I cannot or do not want to have the required liver biopsies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HTD1801 or placebo, 1250 mg BID, for up to 60 weeks

60 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HTD1801
• Placebo

Trial Overview The study is testing HTD1801 against a placebo in people with NASH and liver fibrosis who also have type 2 diabetes or pre-diabetes. It's a phase 2b trial where participants are randomly assigned to either receive HTD1801 or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: HTD1801 Experimental Treatment 1 Intervention

HTD1801,1250 mg, BID

Group II: placebo Placebo Group 1 Intervention

placebo, BID

Who Is Running the Clinical Trial?

HighTide Biopharma Pty Ltd

Lead Sponsor

Trials

12

Recruited

2,000+

Published Research Related to This Trial

In a study of 187 participants with nonalcoholic steatohepatitis (NASH) receiving placebo treatment, 20% showed a significant reduction in liver fat content (PDFF) after 12 weeks, highlighting a notable 'placebo effect' that can impact trial outcomes.

The analysis revealed an average decrease of 2.3 units in absolute PDFF values after 24 weeks of placebo treatment, suggesting that future clinical trials should account for this effect when calculating sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Nedrud, MA., Chaudhry, M., Middleton, MS., et al.[2023]

In a review of 15 randomized controlled trials involving both adults and children, metformin showed a significant effect on normalizing alanine transaminase levels compared to vitamin E, indicating its potential efficacy in treating nonalcoholic fatty liver disease (NAFLD).

While some treatments like pioglitazone showed reduced liver necrosis and inflammation, the overall limited data and methodological issues in the studies prevent definitive conclusions about the efficacy of various pharmacological and dietary interventions for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: a systematic review. Socha, P., Horvath, A., Vajro, P., et al.[2022]

Non-alcoholic fatty liver disease (NAFLD) is a growing global health issue linked to metabolic disorders, with significant risks for disease progression and mortality, yet there are currently no approved medications for its treatment.

This paper reviews emerging therapeutic strategies and potential drug targets for NAFLD, emphasizing the importance of ongoing clinical trials in developing effective pharmacotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Prikhodko, VA., Bezborodkina, NN., Okovityi, SV.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12260645/

HTD1801 demonstrates promising potential for histologic ... Berberine ursodeoxycholate (HTD1801) has been shown to significantly reduce liver fat content (LFC) in an 18-week, placebo-controlled Phase 2 study.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05623189

HTD1801 in Adults With Nonalcoholic Steatohepatitis and ... The total range for non-alcoholic fatty liver disease activity score (NAS) is between 0 to 8. The lower the score the better the outcome. Up to 60 Weeks ...

3. nature.com nature.com/articles/s41467-021-25701-5

A phase 2, proof of concept, randomised controlled trial ... Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40258699/

HTD1801 demonstrates promising potential for histologic ... These findings suggest that HTD1801 has strong potential to produce histological improvements in patients with MASH.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03656744

NCT03656744 | A Study of HTD1801 in Adults With ... 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 ...