DD01 for Fatty Liver Disease

Not currently recruiting at 11 trial locations

Overseen By Senior Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Neuraly, Inc.

Must not be taking: Corticosteroids, Insulin, GLP-1 agonists, others

Disqualifiers: Liver disease, Obesity surgery, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests DD01, a new treatment for individuals with fatty liver disease linked to being overweight or having metabolic issues. The researchers aim to determine if DD01 can improve liver health in those with MASLD or MASH, conditions caused by fat buildup and inflammation in the liver. Participants will receive either DD01 or a placebo (a harmless pill with no active drug). The trial seeks individuals who are overweight, have a confirmed fatty liver condition, and meet specific health criteria, such as a stable body weight and certain waist measurements. As a Phase 2 trial, this research focuses on assessing DD01's effectiveness in an initial, smaller group of participants.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using certain therapies like systemic corticosteroids, methotrexate, or insulin for diabetes, you may not be eligible to participate.

Is there any evidence suggesting that DD01 is likely to be safe for humans?

Research has shown that DD01 is generally safe and easy for people to handle. In earlier studies, DD01 helped reduce liver fat and improve liver health. Participants in these studies experienced few side effects, and the treatment was easy to tolerate. One study specifically found that DD01 was safe and effective in reducing fatty liver, with no major safety issues reported. This indicates that DD01 has a strong safety record, supporting its use in trials like this one. ^{1 2 3 4 5}

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

Most treatments for fatty liver disease focus on lifestyle changes or medications that address symptoms like insulin resistance or high cholesterol. But DD01 works differently, targeting the root cause of liver fat accumulation itself. Researchers are excited about DD01 because it uses a novel mechanism of action that directly reduces liver fat, potentially offering a more effective solution. Unlike traditional treatments, which can take time to show benefits, DD01 aims to provide quicker, more direct results in managing fatty liver disease.

What evidence suggests that DD01 might be an effective treatment for fatty liver disease?

Research has shown that DD01, which participants in this trial may receive, may help treat fatty liver disease. In one study, after 12 weeks of using DD01, patients experienced an average liver fat reduction of 62.3%, while those taking a placebo saw only an 8.3% reduction. Another study found that up to 100% of patients experienced significant liver fat reduction after just four weeks. DD01 has also been generally safe and well tolerated by patients. Overall, these findings suggest DD01 could be an effective option for reducing liver fat in people with fatty liver disease. ^{2 6 7 8 9}

Who Is on the Research Team?

Dennis To

Principal Investigator

Neuraly, Inc.

Are You a Good Fit for This Trial?

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.

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

Participants must have the ability and willingness to comply with all Protocol procedures, provide written informed consent and meet all inclusion criteria as outlined in the study protocol

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DD01 or placebo for 48 weeks to evaluate efficacy, safety, and tolerability

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DD01

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

Current treatments for nonalcoholic fatty liver disease (NAFLD) are still not very effective, but weight loss remains a key target for therapy despite being difficult to achieve.

Several investigational drugs show promise for treating NASH, but concerns about long-term safety exist, particularly with vitamin E and other medications like pioglitazone and obeticholic acid, which have notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for nonalcoholic steatohepatitis - a safety evaluation. Issa, D., Wattacheril, J., Sanyal, AJ.[2017]

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]

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]

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]

In a randomized, double-blind, placebo-controlled trial involving 99 patients with non-alcoholic fatty liver disease (NAFLD), the Tiaogan Lipi Recipe (TLR) combined with lifestyle changes significantly improved clinical symptoms and liver function compared to a placebo after 12 weeks.

The treatment group showed greater reductions in liver enzymes (ALT, AST, GGT) and better overall liver/spleen CT ratios, indicating effective liver protection and anti-inflammatory effects, with a total effective rate of 79.69% for TLR compared to 56.25% for the placebo group.

NCBI (Pubmed)

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]. Yu, Q., Zhang, SS., Zhou, T., et al.[2018]

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]

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]

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]

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]

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]

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]

Citations

1. biospace.com biospace.com/d-and-d-pharmatech-announces-rapid-clinically-significant-reductions-in-liver-fat-achieved-in-four-weeks-treating-nafld-patients-with-dd01-a-novel-long-acting-glp-1-glucagon-receptor-agonist

D&D Pharmatech Announces Rapid, Clinically Significant ... Following only four (4) weeks of once-weekly treatment, up to 100% of patients achieved >30% liver fat reduction by MRI-PDFF. A mean relative ...

2. businesswire.com businesswire.com/news/home/20250616477730/en/DD-Pharmatech-Announces-Positive-Phase-2-Results-for-DD01-in-MASH-with-Robust-Reductions-in-Liver-Fat-Accompanied-by-Improvements-in-Liver-and-Metabolic-Health

D&D Pharmatech Announces Positive Phase 2 Results for ... DD01 achieved a mean reduction of liver fat content of 62.3% vs 8.3% for placebo at 12 weeks of treatment, and 48.5% of DD01 subjects achieved ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04812262

A Phase 1 Study of DD01 in Overweight/Obese Subjects ... This is a Phase 1, first in human (FiH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study ...

4. liverdiseasenews.com liverdiseasenews.com/news/dosing-begins-clinical-trial-dd01-treat-fatty-liver-disease/

Dosing begins in clinical trial of DD01 in treating fatty liver... Results, released last year, showed that DD01 was generally safe and well tolerated at weekly doses of up to 80 mg. Up to 100% of MASLD patients ...

5. firstwordpharma.com firstwordpharma.com/story/5842820

D&D Pharmatech Granted Fast Track Designation from US ... In that study, DD01 treatment was well tolerated and reduced hepatic steatosis by >50% in only 4 weeks with up to 100% of subjects achieving ≥30 ...

6. biospace.com biospace.com/press-releases/d-d-pharmatech-announces-positive-phase-2-results-for-dd01-in-mash-with-robust-reductions-in-liver-fat-accompanied-by-improvements-in-liver-and-metabolic-health

D&D Pharmatech Announces Positive Phase 2 Results for ... DD01 achieved a mean reduction of liver fat content of 62.3% vs 8.3% for placebo at 12 weeks of treatment, and 48.5% of DD01 subjects achieved ...

7. liverdiseasenews.com liverdiseasenews.com/news/clinical-trial-dd01-treat-mash-fatty-liver-disease-enrolled/

Phase 2 trial of DD01 in treating MASH completes enrollment In MASLD patients, average liver fat content was reduced by more than 30%, and markers of glucose, blood fat, and liver damage also lowered.

8. firstwordpharma.com firstwordpharma.com/story/5734626

D&D Pharmatech Announces Rapid, Clinically Significant ... Study results demonstrate DD01 was safe and well-tolerated at doses highly effective in reducing fatty liver.

9. finance.yahoo.com finance.yahoo.com/news/d-d-pharmatech-announces-positive-100000657.html

D&D Pharmatech Announces Positive Phase 2 Results for ... Results of a planned 12-week assessment of safety and efficacy revealed DD01 was well tolerated, and the study's primary endpoint was met.