Effectiveness and safety of LM011 in treating subjects diagnosed with non-alcoholic steatohepatitis (NASH).

LM-011-18-01 is a single arm open label study to test the safety and effectiveness of LM-011 in patients diagnosed with “nonalcoholic steatohepatitis’ (NASH). 20 NASH patients will be enrolled and receive orally LM011 once a day for a duration of 16 weeks. All patients will undergo dose adjustment to reach a desirable target dose following the guidance in the protocol. Subjects will receive 4 loading doses on Day 1, and one daily maintenance dose starting on Day 2. The loading doses range from 12.5 mL/day to 25 mL/day based on the participant's lean body weight. The initial maintenance dose ranges from 2.5 mL/day to 5 mL/day, also based on the participant's lean body weight. The therapeutic window of LM011 is narrow with a desired target range of 0.7-1 ng/mL, as such, plasma concentration will be monitored on an ongoing basis. Blood samples will be collected starting at Visits 2, 3, 4, 5 and 6 or at Early Termination. If LM011 plasma concentration is determined to be outside the target range of 0.7 – 1 ng/mL or if clinically significant adverse events related to study drug are reported or significant lean body weight change compared to baseline, the investigator will adjusts the dose according to the guidance of the protocol. Adherence to the intervention will be monitored in two ways: 1. A primary compliance measurement will be calculated based on the volumes provided in Participants’ Dosing Diary. This will be manually entered into the Viedoc EDC system on the Drug Compliance eCRF by the site staff at each visit upon return of the dosing diary by the participant, and will be verified by the CRA during each monitoring visit. Compliance (%) = [Volume of LM011 Used (mL) ÷ Expected Volume of LM011 Expected (mL)] x 100 Volume of LM011 Used (mL) will be determined by the Actual Dose Administered (mL) from the participants’ diaries. Volume of LM011 Expected (mL) will be determined by number of doses expected for the duration between scheduled visits. 2. A secondary check of compliance will be performed through weighing of LM011 bottles prior to dispensing to participants and upon return of LM011 bottles from participants at the next scheduled visit. The weight of the IP bottles before dispensing and upon return of unused and partially used bottles will be entered into the Viedoc EDC system on the Drug Accountability eCRF. The compliance will be programmatically calculated outside of the EDC system and a report will be generated on a weekly basis for CRA review. The CRA will reconcile the primary and secondary compliance values, and follow up with sites where any discrepancies are noted. Participant retraining will be required if inconsistencies are apparent, and further escalation to the CRO and Sponsor will be necessary where inconsistencies are noted more than once. If necessary, such patients will be dropped from the study. Calculations of Amount of LM011 Taken by Patients Volume LMO11 Used (mL) = Mass of LM011 (g) Used ÷ Density (g/cm3) Where the Density of LM011 = 1.11 g/cm3 Calculations of Compliance Compliance (%) = [(Volume LM011 Used ÷ Volume LMO11 Prescribed)] X 100 In addition to the monitoring described above, site staff will also reinforce the importance of drug compliance with the patient during scheduled visits as well as during telephone calls with the patients, e.g. when the LM011 concentration results become available, or during general telephone contact calls with the patient as applicable.