Trial Outcomes & Findings for Open-Label Study To Evaluate MN-001 on HDL & Triglyceride in NASH & NAFLD Subjects (NCT NCT02681055)

Last Updated: 2023-03-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Baseline, 12 weeks

Results posted on

2023-03-15

Participant Flow

Participant milestones

Participant milestones
Measure	Open Label Arm All subjects will take MN-001 250 mg once a day for the first 4 weeks. After 4 weeks of MN-001 250 mg once a day, all subjects will take MN-001 250 mg twice a day for the remaining 8 weeks of the treatment phase. Subjects will receive MN-001 for a total of 12 weeks.
Weeks 1-4 STARTED	19
Weeks 1-4 COMPLETED	19
Weeks 1-4 NOT COMPLETED	0
Weeks 5-12 STARTED	19
Weeks 5-12 COMPLETED	18
Weeks 5-12 NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Open Label Arm All subjects will take MN-001 250 mg once a day for the first 4 weeks. After 4 weeks of MN-001 250 mg once a day, all subjects will take MN-001 250 mg twice a day for the remaining 8 weeks of the treatment phase. Subjects will receive MN-001 for a total of 12 weeks.
Weeks 5-12 Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Age, Continuous	54.6 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Outcome measures

Outcome measures
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity	-0.013 percentage of cholesterol Standard Deviation 0.1022

PRIMARY outcome

Timeframe: 8 weeks

Change from baseline to 8 weeks of MN-001 on serum triglyceride levels in NASH subjects with hypertriglyceridemia

Outcome measures

Outcome measures
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Mean Change From Baseline to Week 8 on Triglyceride Levels After 8 Weeks MN-001 Treatment	-21.67 mg/dL Standard Deviation 27.89

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12 and 13

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Number of Treatment-emergent Adverse Events All-cause mortality	0 number of adverse events
Number of Treatment-emergent Adverse Events serious adverse events	0 number of adverse events
Number of Treatment-emergent Adverse Events adverse events	18 number of adverse events

SECONDARY outcome

Timeframe: 24 hours

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.

Outcome measures

Outcome measures
Measure	Open Label Arm n=6 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Mean Plasma Concentration of MN-001 and MN-002 (Metabolite) After a Single Dose of MN-001 in Six Subjects Mean plasma concentration of MN-001 after a single dose of MN-001 250 mg	0.434 mcg/mL Standard Deviation 0.205
Mean Plasma Concentration of MN-001 and MN-002 (Metabolite) After a Single Dose of MN-001 in Six Subjects Mean plasma concentration of MN-002 after a single dose of MN-001 250 mg	3.44 mcg/mL Standard Deviation 2.40

SECONDARY outcome

Timeframe: Baseline, Week 8

Mean change from baseline to week 8 on total cholesterol, high-density lipoproteins, low-density lipoproteins

Outcome measures

Outcome measures
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Mean Serum Lipids From Baseline to Week 8 Total cholesterol	-15.2 mg/dL Standard Deviation 41.34
Mean Serum Lipids From Baseline to Week 8 high-density lipoproteins	3.2 mg/dL Standard Deviation 7.61
Mean Serum Lipids From Baseline to Week 8 low-density lipoproteins	-13.7 mg/dL Standard Deviation 55.31

SECONDARY outcome

Timeframe: Baseline, Week 8

Measure the effect of MN-001/002 on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) mean change from Baseline to Week 8

Outcome measures

Outcome measures
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Mean Change in Liver Enzymes From Baseline to Week 8 alanine aminotransferase	-5.7 U/L Standard Deviation 22.79
Mean Change in Liver Enzymes From Baseline to Week 8 aspartate aminotransferase	1.2 U/L Standard Deviation 22.7

SECONDARY outcome

Timeframe: Baseline and Week 12

To measure the effect of MN-001/002 on percentage of fat in the liver by MRI mean change from baseline to Week 12

Outcome measures

Outcome measures
Measure	Open Label Arm n=19 Participants All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Measure the Effect of MN-001/002 on Percentage of Fat in the Liver	0.64 percentage of fat in liver Standard Deviation 5.54

Adverse Events

Open Label Arm

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Open Label Arm n=19 participants at risk All 19 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. MN-001: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Gastrointestinal disorders diarrhea	10.5% 2/19 • Number of events 2 • 13 weeks
Gastrointestinal disorders constipation	5.3% 1/19 • Number of events 1 • 13 weeks
Gastrointestinal disorders nausea	5.3% 1/19 • Number of events 1 • 13 weeks
Infections and infestations ear infection	5.3% 1/19 • Number of events 1 • 13 weeks
Infections and infestations nasopharyngitis	5.3% 1/19 • Number of events 1 • 13 weeks
Investigations alanine aminotransferase increased	5.3% 1/19 • Number of events 1 • 13 weeks
Investigations aspartate aminotransferase increased	5.3% 1/19 • Number of events 1 • 13 weeks
Investigations heart rate increased	5.3% 1/19 • Number of events 1 • 13 weeks
Musculoskeletal and connective tissue disorders arthralgia	5.3% 1/19 • Number of events 1 • 13 weeks
Musculoskeletal and connective tissue disorders myalgia	5.3% 1/19 • Number of events 1 • 13 weeks
Musculoskeletal and connective tissue disorders pain in extremity	5.3% 1/19 • Number of events 1 • 13 weeks
Nervous system disorders hypoaesthesia	5.3% 1/19 • Number of events 1 • 13 weeks
Nervous system disorders paraesthesia	5.3% 1/19 • Number of events 1 • 13 weeks
Cardiac disorders bundle branch block left	5.3% 1/19 • Number of events 1 • 13 weeks
Respiratory, thoracic and mediastinal disorders rhinorrhea	5.3% 1/19 • Number of events 1 • 13 weeks
Skin and subcutaneous tissue disorders pigmentation disorder	5.3% 1/19 • Number of events 1 • 13 weeks
Vascular disorders phlebitis	5.3% 1/19 • Number of events 1 • 13 weeks

Additional Information

Director, Research and Development

MediciNova, Inc.

Phone: 8583444535

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60