MN-001 for Non-alcoholic Fatty Liver Disease

Recruiting at 1 trial location

Overseen By Rashmee Patil, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: MediciNova

Must be taking: Oral antidiabetics

Disqualifiers: Chronic liver disease, Advanced liver fibrosis, Diabetes type 1, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The design of the Phase 2 clinical trial includes the following elements: * Multi-center, two-arm, randomized, double-blind, placebo-controlled trial to evaluate MN-001 (tipelukast) vs. placebo in approximately 40 patients in the U.S. * Patients will be randomized 1:1 to receive either 500 mg/day of MN-001 (tipelukast) or placebo for 24 weeks. * The co-primary endpoints are (1) change from baseline in liver fat content measured by controlled attenuation parameter (CAP) score at Week 24, and (2) change from baseline in fasting serum triglycerides at Week 24. FibroScan® is a non-invasive, quantitative, and accurate measure of liver fat content commonly used in early phase trials to measure treatment response. * Secondary endpoints include safety and tolerability and changes in lipid profile (HDL-C, LDL-C, and total cholesterol).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable dose of oral antidiabetic therapy for at least 3 months before joining the trial.

How is the drug MN-001 different from other treatments for non-alcoholic fatty liver disease?

MN-001 (Tipelukast) is unique because it is being studied specifically for its potential to treat non-alcoholic fatty liver disease, whereas most current treatments focus on lifestyle changes and a few drugs that have not shown sustained results after stopping treatment. ^{1 2 3 4 5}

What data supports the effectiveness of the drug MN-001 (Tipelukast) for treating non-alcoholic fatty liver disease?

A study on montelukast, a similar drug, showed significant improvement in liver stiffness and liver enzymes in patients with non-alcoholic steatohepatitis (NASH), a more severe form of non-alcoholic fatty liver disease (NAFLD). This suggests that MN-001, which is related to montelukast, might also be effective for NAFLD. ^{1 6 7 8 9}

Who Is on the Research Team?

Kazuko Matsuda, MD PhD MPH

Principal Investigator

Medicinova Inc

Are You a Good Fit for This Trial?

This trial is for adults with Non-alcoholic Fatty Liver Disease and Type 2 Diabetes who have high triglycerides, are on stable diabetes medication, and show a certain level of liver fat. People can't join if they've had significant weight changes recently, certain gastrointestinal issues or surgeries, advanced liver fibrosis or cirrhosis, recent severe heart events, or other specific liver diseases.

Inclusion Criteria

Your blood triglyceride levels are higher than 150 mg/dL after fasting.

I have been on a consistent dose of diabetes medication for at least 3 months.

Your FibroScan® CAP score is higher than 248 dB/m in the last 8 weeks.

Exclusion Criteria

I have no stomach or bowel problems that could affect medicine absorption.

I have had a serious heart problem in the last 6 months.

I have a severe scarring of the liver.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 500 mg/day of MN-001 (tipelukast) or placebo for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MN-001
• MN-001 placebo

Trial Overview The study tests MN-001 (tipelukast) against a placebo in about 40 patients to see its effect on liver fat content and fasting serum triglycerides over 24 weeks. Patients will be randomly assigned to either the drug or placebo group in equal numbers.

How Is the Trial Designed?

Group I: MN-001 Experimental Treatment 1 Intervention

Group II: MN-001 Placebo Placebo Group 1 Intervention

The placebo comparator is a tablet identical in appearance to MN-001.

MN-001 is already approved in European Union, Canada for the following indications:

Approved in European Union as Tipelukast for:

• Scleroderma
• Systemic sclerosis

Approved in Canada as Tipelukast for:

• Scleroderma
• Systemic sclerosis

Who Is Running the Clinical Trial?

MediciNova

Lead Sponsor

Trials

21

Recruited

1,500+

Published Research Related to This Trial

In a randomized trial involving 127 patients with nonalcoholic fatty liver disease (NAFLD), diisopropylamine dichloroacetate demonstrated significant efficacy, with 87.8% improvement in symptoms for the high dosage group and 79.6% for the low dosage group after 8 weeks.

The treatment was found to be safe, with only mild adverse effects reported (dryness of the mouth in 1.6% of cases) and no severe adverse reactions, indicating that diisopropylamine dichloroacetate is a viable option for NAFLD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver disease: a multicenter random double-blind controlled trial]. Lu, LG., Zeng, MD., Mao, YM., et al.[2005]

A systematic review of 11 randomized controlled trials involving 936 middle-aged individuals found that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduced liver fat content and serum liver enzyme levels in patients with nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) over a median treatment duration of 26 weeks.

GLP-1 RAs, particularly liraglutide and semaglutide, also showed greater histological resolution of NASH without worsening liver fibrosis, indicating their potential as effective treatments for these liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Mantovani, A., Petracca, G., Beatrice, G., et al.[2021]

Pioglitazone and vitamin E may help treat NAFLD/NASH in some adults with type 2 diabetes, but newer drugs like selective PPAR-γ modulators (SPPARMs) and GLP-1 receptor agonists show even better results with fewer side effects based on recent studies.

SGLT2 inhibitors and statins may also improve NAFLD/NASH in patients with type 2 diabetes, suggesting that a combination of these newer treatments could significantly reduce liver and cardiovascular risks, although more extensive trials are needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Alcoholic Fatty Liver Disease Treatment in Patients with Type 2 Diabetes Mellitus; New Kids on the Block. Athyros, VG., Polyzos, SA., Kountouras, J., et al.[2020]

In a randomized double-blind placebo-controlled study of 52 overweight/obese patients with non-alcoholic steatohepatitis (NASH), montelukast significantly improved liver stiffness and various liver function markers after 12 weeks compared to placebo.

Montelukast was well tolerated and did not increase depressive symptoms, suggesting it could be a safe and effective treatment option for patients with NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The leukotriene receptor antagonist montelukast in the treatment of non-alcoholic steatohepatitis: A proof-of-concept, randomized, double-blind, placebo-controlled trial. Abdallah, MS., Eldeen, AH., Tantawy, SS., et al.[2021]

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]

The study of 305 Italian patients with non-alcoholic fatty liver disease revealed that the typical patient is a young, overweight or obese male, often with dyslipidaemia and hyperinsulinaemia, but not necessarily diabetic.

Histological analysis showed that 80% of patients had steatosis with mild inflammation and fibrosis, indicating that liver biopsy is essential for accurately assessing liver damage, as no single factor was identified as a reliable predictor of hepatic lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver. Loguercio, C., De Simone, T., D'Auria, MV., et al.[2015]

Lifestyle changes, such as weight loss and increased physical activity, are the primary recommended strategies for managing nonalcoholic fatty liver disease (NAFLD), as they are essential for preventing progressive liver failure.

While some pharmacological treatments have shown improvements in liver biochemistry, only a few have demonstrated benefits in liver histology, and these effects do not last after treatment ends, indicating that more research is needed before these drugs can be recommended outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which treatment for nonalcoholic fatty liver disease? Moscatiello, S., Marzocchi, R., Villanova, N., et al.[2019]

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]

In a 16-week study involving 102 participants with nonalcoholic fatty liver disease (NAFLD), AXA1125 demonstrated significantly greater improvements in key metabolic and fibroinflammatory markers compared to placebo, including a 22.9% reduction in liver fat content (MRI-PDFF) and a 21.9% decrease in alanine aminotransferase (ALT).

AXA1125 was found to be safe and well-tolerated, with a higher proportion of subjects achieving clinically relevant improvements in liver health compared to those receiving AXA1957 or placebo, indicating its potential as a promising treatment for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease. Harrison, SA., Baum, SJ., Gunn, NT., et al.[2023]

Citations

1. China pubmed.ncbi.nlm.nih.gov

[Diisopropylamine dichloroacetate in the treatment of nonalcoholic fatty liver disease: a multicenter random double-blind controlled trial]. [2005]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. [2021]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Non-Alcoholic Fatty Liver Disease Treatment in Patients with Type 2 Diabetes Mellitus; New Kids on the Block. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The leukotriene receptor antagonist montelukast in the treatment of non-alcoholic steatohepatitis: A proof-of-concept, randomized, double-blind, placebo-controlled trial. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver. [2015]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Which treatment for nonalcoholic fatty liver disease? [2019]

8. Pakistan pubmed.ncbi.nlm.nih.gov

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

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

Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease. [2023]