A study investigating the safety, absorption and elimination of FM101, a new compound in the treatment of non-alcoholic fatty liver disease.

Phase 1

Conditions: onalcoholic Fatty Liver Disease (NAFLD) or Nonalcoholic Steatohepatitis (NASH)
MedDRA version: 22.0Level: LLTClassification code 10029530Term: Non-alcoholic fatty liverSystem Organ Class: 10019805 - Hepatobiliary disorders
MedDRA version: 22.0Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2020-005187-63-HU

Lead Sponsor: Future Medicine Co., Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 60

Inclusion Criteria

1. Be able and willing to provide written informed consent to take part in the study and to comply with all the study’s requirements.
2. Be a man or woman =18 years of age at screening.
3. Have
a. Histologic confirmation of NASH no more than 12 months before the screening visit date, demonstrating the existence of steatosis =5%, hepatocyte ballooning and chronic inflammation (at least 1 point for each component), and stage 1 through stage 3 liver fibrosis according to the NASH Clinical Research Network (CRN); OR
b. NAFLD based upon demonstration of at least 3 of the following 5 components of the metabolic syndrome below, at screening:
• FPG =100 mg/dL (=5.6 mmol/L), or undergoing drug treatment for elevated plasma glucose concentrations
• HDL-C concentration <40 mg/dL in male patients, or <50 mg/dL in female patients, or undergoing drug treatment for reduced serum HDL-C concentrations
• Serum triglyceride (TG) concentration =150 mg/dL, or undergoing drug treatment for elevated serum TG concentrations
• Waist circumference >102 cm in male patients or >88 cm in female patients
• Systolic blood pressure =130 mm Hg or diastolic blood pressure =85 mm Hg, or undergoing drug treatment for hypertension, or antihypertensive drug treatment in a patient with a history of systemic hypertension
4. Serum ALT concentration >1 × ULN at screening
5. FIB-4 result >1.3 and =3.25, at screening:
• If the FIB-4 result is =1.3 but =1.45, OR >2.67 and =3.25, the patient must undergo Fibroscan (VCTE) before proceeding to MRI studies.
• The Fibroscan (VCTE) result must be >4 kPa but =12.5 kPa.
• If such a Fibroscan (VCTE) result exists from the 3-month period before screening visit date, this result may be used.
6. Undergo MRI-PDFF that demonstrates =8% liver steatosis during the screening period.
7. Undergo MRI-MRE with a score =2.9 kPa during the screening period.
8. WOCBP must have a negative serum ß-human chorionic gonadotropin test result at screening.
Female patients must agree to use at least 1 highly effective birth control throughout the study and up to 30 days after the last dose of study drug has been taken. Highly effective contraception measures include the following options, but are not limited to:
• Combined estrogen- and progestogen-containing hormonal contraception (administration may be oral, intravaginal, or transdermal);
• Progestogen-only hormonal contraception associated with inhibition of ovulation (administration may be oral, injectable, or implantable);
• Intrauterine device, intrauterine hormone-releasing system, bilateral tubal, occlusion (‘tubal occlusion’ includes ‘tubal ligation’);
• Vasectomized partner (provided that the male has provided confirmation of surgical success and in the event that the vasectomized partner is the sole sexual partner of the woman of childbearing potential);
• Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk in relation to the duration of the clinical trial), only in the event that this is the preferred lifestyle of the patient.
Childbearing potential is defined as being fertile after menarche and until becoming postmenopausal unless permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
A postmenopausal state is defined as no menses for =12 consecutive months without an alternative medical cause.
Men with partners who are WOCBP must either be surgically sterile or agree to use a barrier contraceptive f

Exclusion Criteria

1. Any patient who refuses to provide written informed consent to take part in the study, and/or appears unwilling to comply with study-specific requirements
2. Female persons who are pregnant or are breastfeeding at screening, or who plan to become pregnant during the study
3. BMI <25 kg/m2
4. Any of the laboratory test abnormalities at screening (see the list in the protocol section 8.2 Exclusion Criteria)
5. Chronic liver disease other than confirmed NASH or NAFLD, including but not limited to the diagnoses/entities (see the list in the protocol section 8.2 Exclusion Criteria)
6. Medical, histologic, and/or imaging history of hepatic cirrhosis
7. Clinical, endoscopic, imaging and/or laboratory manifestations of portal hypertension, such as spider nevi, splenomegaly, clinically evident ascites formation, nonbleeding gastro-oesophageal varices
8. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness
9. Chronic use (=12 months) of any drug known to be associated with development of NAFLD during the 5 years before the anticipated Day 1 visit date (eg, amiodarone, methotrexate, systemic glucocorticoids [unless employed at physiologic replacement doses for management of confirmed adrenal insufficiency], tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement therapy, anabolic steroids [other than testosterone replacement preparations being taken at a physiologic replacement dose for management of confirmed male hypogonadism], sodium valproate, and other hepatotoxins such as minocycline)
10. Use of the medications (see the list in the protocol section 8.2 Exclusion Criteria)
11. History of significant alcohol consumption, defined as an average of >20 g/day in female patients and >30 g/day in male patients, for a period of >3 consecutive months within 1 year before screening, hazardous alcohol use (Alcohol Use Disorders Identification Test score =8), or an inability to reliably quantify alcohol consumption based upon judgment of the investigator
12. Use of legally prohibited substance or substances within 1 year before the screening visit date in a manner that may jeopardize the patient’s willingness and/or ability to complete study requirements, in the judgment of the investigator.
13. Weight change =7% within the 6 months before screening or =5% within the 3 months before screening
14. Prior or planned (during the study period) weight reduction surgery (eg, sleeve gastrectomy, Roux-en-Y gastrojejunostomy)
15. Type 1 diabetes mellitus by medical history
16. Poorly controlled type 2 diabetes mellitus (this is defined as HbA1c >9.5% at screening, or a patient whose oral antidiabetic medication dosing requires adjustment >10% less than 2 months before the screening visit date).
17. Uncontrolled systemic hypertension (either treated or untreated) defined as systolic blood pressure >160 mm Hg or a diastolic blood pressure >100 mm Hg at screening. A retest of blood pressure, (after establishing good blood pressure control within a reasonable period of time and up to the Baseline visit) is permissible at the discretion of the investigator
18. Patients who demonstrate recent evidence (within 6 months of the anticipated date of the Day 1 visit) of clinically evident and significant atheromatous cardiovascular disease (eg, unstable angina, acute coronary syndrome, myocardial infarction, cerebrovascular accident [stroke], cerebrovascular ischemia, transien

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of 13 weeks of treatment with FM101 in patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH)<br><br>To assess the treatment effect of FM101 on serum alanine aminotransferase (ALT) concentrations after 13 weeks of treatment<br><br>;Secondary Objective: To assess the effect of 13 weeks of treatment with FM101 on the change in liver stiffness (kPa) measured by magnetic resonance imaging- (MRI)-magnetic resonance elastography (MRE) in patients with NAFLD or NASH<br>;Primary end point(s): 1. Number and percentage of patients with TEAEs, related TEAEs, and/or severe TEAEs [Time Frame: From administration of FM101 on Day 1 to the last follow up visit] <br>2. Change from Baseline to postbaseline assessments during 13 weeks of treatment in serum ALT concentrations<br>;Timepoint(s) of evaluation of this end point: 1. Time Frame: From administration of FM101 on Day 1 to the last follow up visit<br>2. during 13 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Changes from Baseline to Week 13 in liver stiffness (kPa) on MRE. ;Timepoint(s) of evaluation of this end point: From Baseline to Week 13

Related Trials