Non-alcoholic SteatohepatitisPhase 2NCT02681055

Open-Label Study To Evaluate MN-001 on HDL & Triglyceride in NASH & NAFLD Subjects

A Phase 2 study testing MN-001 in people with Non-alcoholic Steatohepatitis and Hypertriglyceridemia, run by MediciNova at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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 steatohepatitis (NASH) and Non-Alcoholic Fatty Liver Disease (NAFLD) subjects with hypertriglyceridemia. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-alcoholic Steatohepatitis, Hypertriglyceridemia, Non-alcoholic Fatty Liver Disease
What is being tested?: MN-001
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 3 sitesUnited States
Study dates: Mar 2016to 1 Oct 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator.
Male or female subjects ≥ 18 years of age
Histologically proven NASH (NAFLD activity score of 3 or greater with at least 1 point being ballooning) based on liver biopsy performed within the last 36 months or abdominal ultrasound confirmation of non-alcoholic fatty liver disease (NAFLD)
Fasting serum triglyceride level > 150 mg/dL (confirmed at screening)
Serum ALT, AST, ALP and total bilirubin levels at Screening (- 120 days to -30 days) and Lab Visit values (- 1 week ± 5 days) are stable or changes at the Lab visit are < 20% of the values from Screening.
BMI ≤ 45 kg/m2

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Subjects on the following medications can be enrolled if these medications are necessary, cannot be stopped, and the dose has been stable for 4 months or more prior to baseline:
Stable doses of anti-diabetic medications
Stable doses of fibrates, statins, niacin, ezetimibe.
Stable doses of Vitamin E for at least 8 weeks
Less than 21 units of alcohol/week for men and 14 units of alcohol/week for women over a 2-year time frame
Females of child-bearing potential must have a negative serum ß-hCG at screening and must be willing to use appropriate contraception (as defined by the investigator) for the duration of study treatment and 30 days after the last dose of study treatment.
Males should practice contraception as follows: condom use and contraception by female partner.
Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening, as defined by the investigator.
Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the study nurse/coordinator and the Investigator.

Who cannot join

Diagnosis of other known cause of liver disease (autoimmune, viral, genetic, drug- or alcohol-induced, or storage disease)
Decompensated or severe liver disease defined by one or more of the following:
biopsy-proven cirrhosis
INR >1.5
Total bilirubin (TBL) > 1.5 x ULN, or > 2 x ULN for unconjugated bilirubin
serum albumin <2.8 g/dL

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ALT or AST > 10 x ULN
evidence of portal hypertension including splenomegaly, ascites, encephalopathy and/or esophageal varices
Current diagnosis of hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound
Uncontrolled diabetes mellitus Type 2
History of bariatric surgery
Greater than 10-pound weight gain or loss in the last 6 months
Clinically significant cardiovascular/cerebrovascular disease, including myocardial infarct within last 6 months, coronary artery intervention, coronary artery bypass, unstable ischemic heart disease, heart failure class III or IV, angina or cerebral vascular accident.
Resting pulse < 50 bpm, SA or AV block, uncontrolled hypertension, or QTcF > 450 ms
History of stomach or intestinal surgery or any other condition that could interfere with or is judged by the Investigator to interfere with absorption, distribution, metabolism, or excretion of study drug.
Any significant laboratory abnormality which, in the opinion of the Investigator, may put the subject at risk
History of malignancy < 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
History of HIV (human immunodeficiency virus), HBV, HCV (cured HCV is not excluded), EBV CMV or other active infection.
Currently has a clinically significant medical condition including the following: neurological, psychiatric, metabolic, immunologic, hematological, pulmonary, cardiovascular (including uncontrolled hypertension), gastrointestinal, urological disorder, or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study. Note: Active medical conditions that are minor or well-controlled are not exclusionary if, in the judgment of the Investigator, they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Safety Monitor should be consulted.
CYP2C8 substrates with a narrow therapeutic index (e.g., paclitaxel) within 15 days prior to study and throughout the study are prohibited.
CYP2C9 substrate with narrow therapeutic index (e.g., phenytoin, S-warfarin, tolbutamide) within 15 days prior to study and throughout the study are prohibited.
Macrolide or quinolone class antibiotics within 15 days of Screening Visit and throughout the study are prohibited.
Steroids within 30 days prior to study drug dosing and throughout the study unless administered for a short term treatment course during the study are prohibited.
History of alcohol or substance abuse (DSM-IV-TR criteria) within 3 months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria) within 12 months prior to screening. The only exceptions include caffeine or nicotine abuse/dependence.
Poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator.
Currently participating, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent.
Unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or was planning to relocate during the study.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Southern California Research Center
Coronado, California, 92118
Scripps Research
La Jolla, California, 92037
Harborview Medical Center
Seattle, Washington, 98104

Other trials in United States

About this study

Official title: 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 Non-Alcoholic Fatty Liver Disease (NAFLD) Subjects With Hypertriglyceridemia

Read the detailed description

The study will consist a Screening Phase (up to 4 months) followed by a Treatment Phase (12 weeks), and a Follow-up visit (within 1 week after the last dose). A total of 40 male and female subjects ≥18 years of age are planned to be enrolled. During the Screening Phase, subjects will be assessed for study eligibility. After signing the informed consent form, the following assessments will be performed: medical history including review of prior and current medications, physical examination including height and body weight, waist circumference, vital signs and an electrocardiogram. Clinical labs, routine chemistries, hematology, coagulation profile, urinalysis and a serum pregnancy test will be collected as well as cytokeratin-18 (CK-18), a biomarker for NASH diagnosis. An alcohol consumption questionnaire will be administered and a MRI scan of the liver will be performed. Serum fibrosis markers, the Fib-4 index (age, AST, ALT, PLT) and NAFLD fibrosis score (age, BMI, AST/ALT ratio, IFG/DM, PLT, Albumin) will be calculated.

Conditions: Non-alcoholic Steatohepatitis, Hypertriglyceridemia, Non-alcoholic Fatty Liver Disease, Hypercholesterolemia
Being tested: MN-001
Keywords: NASH, NAFLD
Medical subject headings: Non-alcoholic Fatty Liver Disease, Hypertriglyceridemia, Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MN-001Drug
Also called tipelukast
MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity

Study groups in NCT02681055
Study group	Role	What they receive
open label arm	Experimental	All 40 subjects will receive MN-001 for the first 4 weeks. At Week 4 subjects will increase their dosage frequency for remaining 8 weeks. Subjects will receive MN-001 for a total of 12 weeks. Receives: Drug: MN-001

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity
Change from baseline to 12 weeks of MN-001 on Cholesterol Efflux Capacity (CEC) in NAFLD subjects with hypertriglyceridemia. CEC, a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events and is considered to be a new biomarker to assess cardiovascular risk. Cholesterol efflux was calculated as the percent of cholesterol removed from the cells and appearing in the culture medium normalized to a reference serum pool. The ability of serum HDL to remove cholesterol from cultured cells was assessed as an in vitro method to evaluate functional changes in HDL mediated by changes due to MN-001 treatment.
Measured: Baseline, 12 weeks
Mean Change From Baseline to Week 8 on Triglyceride Levels After 8 Weeks MN-001 Treatment
Change from baseline to 8 weeks of MN-001 on serum triglyceride levels in NASH subjects with hypertriglyceridemia
Measured: 8 weeks

Secondary outcomes (5)

Number of Treatment-emergent Adverse Events
Safety and tolerability of MN-001 by assessing the number of subjects who experienced treatment-emergent adverse events. A treatment-emergent adverse event is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention.
Measured: Baseline, Weeks 2, 4, 8, 12 and 13
Mean Plasma Concentration of MN-001 and MN-002 (Metabolite) After a Single Dose of MN-001 in Six Subjects
Mean plasma concentration of of MN-001 and its metabolite, MN-002, after a single 250 mg oral dose of MN-001 in nonalcoholic steatohepatitis and nonalcoholic fatty liver disease patients.
Measured: 24 hours
Mean Serum Lipids From Baseline to Week 8
Mean change from baseline to week 8 on total cholesterol, high-density lipoproteins, low-density lipoproteins
Measured: Baseline, Week 8
Mean Change in Liver Enzymes From Baseline to Week 8
Measure the effect of MN-001/002 on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) mean change from Baseline to Week 8
Measured: Baseline, Week 8
Measure the Effect of MN-001/002 on Percentage of Fat in the Liver
To measure the effect of MN-001/002 on percentage of fat in the liver by MRI mean change from baseline to Week 12
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 20161 Oct 2019

First posted12 Feb 2016 (estimated)
Study startMar 2016
Primary completion30 May 2018
Study completion1 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Non-alcoholic SteatohepatitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02681055
Sponsor's protocol ID: MN-001-NATG-201
Status last verified: Feb 2023
First submitted: 5 Feb 2016
Last updated: 15 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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 Non-Alcoholic Fatty Liver Disease (NAFLD) Subjects With Hypertriglyceridemia
ClinicalTrials.gov ID: NCT02681055
Acronym / sponsor ID: MN-001-NATG-201
Conditions: Non-alcoholic Steatohepatitis, Hypertriglyceridemia, Non-alcoholic Fatty Liver Disease, Hypercholesterolemia
Keywords: NASH, NAFLD
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: MediciNovaIndustry (pharma, biotech, devices)
Study start: Mar 2016 (actual)
Primary completion: 30 May 2018 (actual)
Study completion: 1 Oct 2019 (actual)
First posted: 12 Feb 2016 (estimated)
Results: Posted 15 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
open label arm	Experimental	Drug: MN-001All 40 subjects will receive MN-001 for the first 4 weeks. At Week 4 subjects will increase their dosage frequency for remaining 8 weeks. Subjects will receive MN-001 for a total of 12 weeks.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Written informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator.
Male or female subjects ≥ 18 years of age
Histologically proven NASH (NAFLD activity score of 3 or greater with at least 1 point being ballooning) based on liver biopsy performed within the last 36 months or abdominal ultrasound confirmation of non-alcoholic fatty liver disease (NAFLD)
Fasting serum triglyceride level > 150 mg/dL (confirmed at screening)
Serum ALT, AST, ALP and total bilirubin levels at Screening (- 120 days to -30 days) and Lab Visit values (- 1 week ± 5 days) are stable or changes at the Lab visit are < 20% of the values from Screening.

Key exclusion criteria (27 listed)

Diagnosis of other known cause of liver disease (autoimmune, viral, genetic, drug- or alcohol-induced, or storage disease)
Decompensated or severe liver disease defined by one or more of the following:
biopsy-proven cirrhosis
INR >1.5
Total bilirubin (TBL) > 1.5 x ULN, or > 2 x ULN for unconjugated bilirubin

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MN-001Also: tipelukastMN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity	Drug	open label arm

Primary outcome

Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity
Time frame: Baseline, 12 weeks
Change from baseline to 12 weeks of MN-001 on Cholesterol Efflux Capacity (CEC) in NAFLD subjects with hypertriglyceridemia. CEC, a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events and is considered to be a new biomarker to assess cardiovascular risk. Cholesterol efflux was calculated as the percent of cholesterol removed from the cells and appearing in the culture medium normalized to a reference serum pool. The ability of serum HDL to remove cholesterol from cultured cells was assessed as an in vitro method to evaluate functional changes in HDL mediated by changes due to MN-001 treatment.
Mean Change From Baseline to Week 8 on Triglyceride Levels After 8 Weeks MN-001 Treatment
Time frame: 8 weeks
Change from baseline to 8 weeks of MN-001 on serum triglyceride levels in NASH subjects with hypertriglyceridemia

5 secondary outcomes

Number of Treatment-emergent Adverse Events
Time frame: Baseline, Weeks 2, 4, 8, 12 and 13
Mean Plasma Concentration of MN-001 and MN-002 (Metabolite) After a Single Dose of MN-001 in Six Subjects
Time frame: 24 hours
Mean Serum Lipids From Baseline to Week 8
Time frame: Baseline, Week 8
Mean Change in Liver Enzymes From Baseline to Week 8
Time frame: Baseline, Week 8
Measure the Effect of MN-001/002 on Percentage of Fat in the Liver
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 15 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Open Label Arm	19	19

Primary outcome: Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity

Time frame: Baseline, 12 weeks. Mean (Standard Deviation). Unit: percentage of cholesterol

Measure	Open Label Arm n = 19
Value	-0.013 (0.1022)

Primary outcome: Mean Change From Baseline to Week 8 on Triglyceride Levels After 8 Weeks MN-001 Treatment

Time frame: 8 weeks. Mean (Standard Deviation). Unit: mg/dL

Measure	Open Label Arm n = 19
Value	-21.67 (27.89)

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: 13 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Open Label Arm	0 of 19 (0%)	10 of 19 (52.6%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Non-alcoholic Steatohepatitis

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ELEVATE-LIVER: A Study to Test Whether Survodutide Helps Improve Heart Structure and Function in People With Overweight or Obesity and Fatty Liver Disease
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Not yet recruitingObservational study
Liver Stiffness Changes by iLivTouch to Predict Liver-Related Events in MAFLD
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Trial of CS060380 Tablets for Non-alcoholic Steatohepatitis (NASH)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kazuko Matsuda, MD PhD MPH study chair

MediciNova

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MN-001 in people with Non-alcoholic Steatohepatitis and Hypertriglyceridemia, run by MediciNova at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity (time frame: Baseline, 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02681055.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2023.