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?

This trial tests a new treatment called MN-001 (Tipelukast) to determine if it can reduce liver fat and improve triglyceride levels in people with non-alcoholic fatty liver disease. Participants will receive either MN-001 or a placebo (a look-alike pill with no active medicine) for 24 weeks. The trial aims to evaluate the effectiveness and safety of MN-001. Suitable candidates have been diagnosed with type 2 diabetes, have high triglycerides, and meet a specific liver fat measure from a FibroScan® test. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MN-001, also known as tipelukast, has been tested in earlier studies for safety and effectiveness. In one study, after 8 weeks of treatment, 14 out of 15 patients had lower triglyceride levels, indicating the treatment's effectiveness. Importantly, the study found that MN-001 was well-tolerated by the patients.

Another study examined MN-001 for non-alcoholic fatty liver disease and found that the treatment had manageable side effects. Since this trial is in Phase 2, the treatment has already passed initial safety tests in smaller groups. While no specific side effects were highlighted, its progression to this phase suggests a good safety record so far.

It's important to remember that any medication can have side effects, and researchers are closely monitoring this during the trial. Prospective participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for non-alcoholic fatty liver disease (NAFLD), which often include lifestyle changes and medications like vitamin E or pioglitazone, MN-001 is unique because it targets leukotrienes and other inflammatory pathways. This new mechanism of action could potentially reduce liver inflammation more effectively than current options. Researchers are excited about MN-001 because it might offer a novel approach by addressing the inflammation directly, which is a critical factor in the progression of NAFLD.

What evidence suggests that MN-001 could be an effective treatment for non-alcoholic fatty liver disease?

In this trial, participants will receive either MN-001 or a placebo. In a previous study, tipelukast (MN-001) showed promise in reducing liver fat and triglycerides in patients with non-alcoholic fatty liver disease (NAFLD). Research has indicated that MN-001 significantly lowered average triglyceride levels in the blood of people with NAFLD. This suggests it might help manage liver fat and improve blood fat levels, which are important for people with this condition. These findings provide hope that MN-001 could effectively treat NAFLD, although more research is needed to confirm its benefits. ^{1 2 3 4 6}

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02681055

NCT02681055 | Open-Label Study To Evaluate MN-001 on ... This is a multi-center, proof-of-principle, open-label study designed to evaluate the efficacy, safety, and tolerability of MN-001 in non-alcoholic ...

2. withpower.com withpower.com/trial/phase-2-fatty-liver-non-alcoholic-fatty-liver-disease-nafld-6-2022-70e06

MN-001 for Non-alcoholic Fatty Liver Disease In a randomized trial involving 127 patients with nonalcoholic fatty liver disease (NAFLD), diisopropylamine dichloroacetate demonstrated significant efficacy, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0223523424006044

Decreasing the burden of non-alcoholic fatty liver disease A phase 3 trial (MAESTRO-NAFLD-1) found that resmetirom was safe, well tolerated, and effective in reducing LDL-C, apoB, triglycerides, hepatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4283712/

Non-alcoholic fatty liver disease is associated with higher ... People with NAFLD spent approximately half an hour extra a day being sedentary (1318±68 vs1289±60 mins/day; p<0.05) and walked 18% fewer steps (8483±2926 vs ...

5. medicinova.com medicinova.com/wp-content/uploads/2018/04/MN-001-NATG-201-ILC2018-final-1-2.pdf

The anti-fibrotic agent tipelukast (MN-001) reduces serum ... Results of the interim analysis shows that tipelukast (MN-001) demonstrates efficacy in significantly reducing mean serum TG level in NASH and NAFLD patients ...

6. synapse.patsnap.com synapse.patsnap.com/drug/73930984856745d78164d267b0d09963

Tipelukast - Drug Targets, Indications, Patents An Open-Label Study To Evaluate The Efficacy, Safety, Tolerability and PK of MN-001 (Tipelukast) on HDL Function and Serum Triglyceride Levels in NASH and ...