DD01 for Fatty Liver Disease

Recruiting in Palo Alto (17 mi)

+11 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Neuraly, Inc.

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase 2 Study to evaluate the effect of DD01 treatment in overweight/obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH).

Do I have to stop taking my current medications for the trial?

The protocol does not specify if you must stop taking your current medications. However, if you are using therapies associated with the development of MASLD/MASH or certain diabetes medications, you may need to stop. Please consult with the trial team for specific guidance.

What data supports the idea that DD01 for Fatty Liver Disease (also known as: DD01) is an effective treatment?

The available research does not provide specific data on the effectiveness of DD01 for treating Fatty Liver Disease. The studies focus on the condition itself, its risk factors, and management strategies, but do not mention DD01 or compare it to other treatments. Therefore, there is no direct evidence from the provided information to support the effectiveness of DD01 for this condition. ^{1 2 3 4 5}

What safety data exists for DD01 treatment in fatty liver disease?

The provided research does not mention DD01 or any alternative names for it directly. However, it discusses various treatments for non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), including berberine ursodeoxycholate (HTD1801) and other investigational drugs. The safety data for HTD1801 indicates it is relatively well tolerated, with diarrhea and abdominal discomfort as the most common adverse events. Other treatments mentioned have associated safety concerns, such as vitamin E's uncertain long-term safety, pioglitazone's risk of osteopenia and weight gain, and obeticholic acid's pruritus. Without specific mention of DD01, it is unclear if these findings are directly applicable. ^{6 7 8 9 10}

Is the drug DD01 a promising treatment for Fatty Liver Disease?

The drug DD01 is considered promising for treating Fatty Liver Disease because it addresses the growing prevalence of the condition, which is linked to obesity and diabetes. Effective treatments like DD01 can help manage the disease and reduce the risk of severe liver damage, improving overall health outcomes. ^{2 11 12 13 14}

Research Team

Dennis To

Principal Investigator

Neuraly, Inc.

Eligibility Criteria

This trial is for overweight or obese individuals who have a liver condition known as MASLD/MASH, which is often linked to excess fat in the liver without heavy alcohol use. Specific criteria for joining are not provided here.

Inclusion Criteria

I have a liver condition with fat buildup confirmed by MRI and either a recent biopsy or 2 metabolic syndrome factors.

I am between 18 and 70 years old.

Participants with a BMI ≥25 kg/m2, with stable body weight by history for 3 months

Exclusion Criteria

Participated in an investigational study within 30 days prior to dosing or who have participated in another MASLD/MASH interventional study within 60 days prior to Screening

I have had serious heart rhythm problems or needed treatment for them in the last 6 months.

A clinically significant physical examination, ECG, or laboratory finding, as judged by the Investigator, may interfere with any aspect of study conduct or interpretation of results

Treatment Details

Interventions

• DD01 (Anti-obesity Agent)

Trial Overview The study tests DD01, a potential new treatment against a placebo (a substance with no active drug) to see its effects on patients with fatty liver diseases related to metabolic issues like obesity.

Participant Groups

Group I: DD01 Experimental Treatment 1 Intervention

Study Drug

Group II: Placebo Placebo Group 1 Intervention

Matching Placebo

Who Is Running the Clinical Trial?

Neuraly, Inc.

Lead Sponsor

Trials

5

Recruited

690+

Findings from Research

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally and is projected to affect over 100 million adults in the U.S. by 2030, highlighting its growing public health concern.

NAFLD can progress from simple fatty liver to more severe conditions like nonalcoholic steatohepatitis and cirrhosis, emphasizing the importance of understanding its risk factors, diagnosis, and management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies. Agyapong, G., Dashti, F., Banini, BA.[2023]

In a study of 50 patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), common clinical features included fatigue (100%), hypertriglyceridemia (80%), and hepatomegaly (72%), indicating a clear pattern of symptoms associated with the disease.

Histopathological analysis revealed that 62% of patients had simple fatty liver, while 38% had nonalcoholic steatohepatitis (NASH), with a significant relationship found between hypertriglyceridemia and the presence of NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical and biochemical profile of biopsy-proven non-alcoholic Fatty liver disease subjects. Khurram, M., Ashraf, MM.[2022]

Children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) have a significantly higher risk of mortality compared to matched general population controls, with a 20-year absolute risk of 7.7% for NAFLD patients versus 1.1% for controls.

The study found that the excess mortality in NAFLD patients is primarily due to cancer, liver disease, and cardiometabolic conditions, with the highest adjusted hazard ratios observed in those with non-alcoholic steatohepatitis (NASH).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality. Simon, TG., Roelstraete, B., Hartjes, K., et al.[2022]

In a study of over 1000 participants, 30.6% were found to have non-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD), with 6.4% showing clinically significant liver fibrosis (LS ≥8.0 kPa).

The study identified that abnormal serum aspartate aminotransferase (AST) and high insulin resistance (HOMA-IR ≥2.5) were strong predictors of significant liver fibrosis, leading to the development of a screening algorithm that effectively identifies at-risk individuals with high sensitivity and negative predictive value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease. Lee, CH., Lui, DT., Li, RH., et al.[2023]

The MAFLD fibrosis score (MFS) was developed and validated in a study involving 707 patients across Malaysia, Hong Kong, and Wenzhou, demonstrating a strong ability to identify advanced fibrosis in metabolic-associated fatty liver disease (MAFLD) with an area under the curve of 0.848 in the training cohort and 0.823 in the validation cohort.

MFS outperformed traditional non-invasive fibrosis scores, achieving a correct prediction rate of 90.4% and an overall diagnostic accuracy of 93.2% when used in conjunction with vibration-controlled transient elastography (VCTE), making it a promising tool for early screening and intervention in MAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease. Cheung, JTK., Zhang, X., Wong, GL., et al.[2023]

DDX3X is primarily expressed in macrophages and hepatocytes, and its down-regulation is associated with nonalcoholic steatohepatitis (NASH) in both human patients and mouse models.

In macrophages, loss of DDX3X leads to reduced inflammation and improved liver health, while in hepatocytes, its absence results in worsened steatohepatitis, highlighting the need for targeted therapies that consider these cell-specific roles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression. Yang, S., Zhou, L., Zhao, T., et al.[2023]

In a study of 100 subjects with non-alcoholic steatohepatitis (NASH) and diabetes, treatment with 1000 mg of berberine ursodeoxycholate twice daily for 18 weeks significantly reduced liver fat content compared to placebo, with a mean decrease of -4.8% versus -2.0%.

The treatment also improved glycemic control and reduced liver-associated enzymes, indicating its potential as an effective therapy for NASH in diabetic patients, although some participants reported mild side effects like diarrhea and abdominal discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Harrison, SA., Gunn, N., Neff, GW., et al.[2022]

Metformin, when combined with weight loss, provides modest improvements in liver fat (steatosis) but does not improve liver scarring (fibrosis) in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).

Thiazolidinediones (TZDs) show positive effects on liver fibrosis and resolution of nonalcoholic steatohepatitis (NASH), although many patients may not respond, indicating the need for long-term treatment to maintain benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety. Mills, EP., Brown, KPD., Smith, JD., et al.[2022]

A new definition for diagnosing metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed by international experts, which includes evidence of liver fat along with criteria like obesity or type 2 diabetes, making it independent of other liver diseases.

This new framework aims to improve the accuracy of MAFLD diagnosis and severity assessment, which could enhance clinical care and research in liver disease, ultimately helping to standardize terminology and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. Eslam, M., Newsome, PN., Sarin, SK., et al.[2023]

Recent research highlights the strong connection between nonalcoholic fatty liver disease (NAFLD) and metabolic disorders, such as obesity and type 2 diabetes, indicating that NAFLD is not just a liver issue but part of a broader metabolic dysfunction.

Promising treatment options for NAFLD/NASH include medications originally designed for type 2 diabetes and obesity, like GLP-1 receptor agonists and SGLT-2 inhibitors, suggesting that these therapies may effectively address both liver health and metabolic risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review. Cariou, B., Byrne, CD., Loomba, R., et al.[2021]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally, affecting 25% of the population, with higher rates in the U.S. (30% for NAFLD and 5% for its more severe form, nonalcoholic steatohepatitis).

Patients with NAFLD who have advanced fibrosis are at significantly higher risk for serious health issues, including increased mortality, highlighting the need for effective identification and management of these patients using noninvasive diagnostic tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. Cotter, TG., Rinella, M.[2021]

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries, affecting about 25% of the population, and is linked to serious health risks like type 2 diabetes and increased mortality from liver and cardiovascular diseases.

Recent evidence indicates that non-alcoholic fatty liver (NAFL), previously thought to be benign, can progress to fibrosis in nearly 25% of cases, highlighting the need for better understanding and monitoring of liver health in affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significance of Simple Steatosis: An Update on the Clinical and Molecular Evidence. Mazzolini, G., Sowa, JP., Atorrasagasti, C., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies. [2023]

2. Pakistan pubmed.ncbi.nlm.nih.gov

A clinical and biochemical profile of biopsy-proven non-alcoholic Fatty liver disease subjects. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

MAFLD fibrosis score: Using routine measures to identify advanced fibrosis in metabolic-associated fatty liver disease. [2023]

6. China pubmed.ncbi.nlm.nih.gov

[Treating non-alcoholic fatty liver disease patients of Gan stagnation Pi deficiency syndrome by tiaogan lidi recipe: a randomized controlled clinical trial]. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Treatment options for nonalcoholic steatohepatitis - a safety evaluation. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. [2021]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Significance of Simple Steatosis: An Update on the Clinical and Molecular Evidence. [2021]