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Trial registered on ANZCTR

Registration number

ACTRN12619000610134

Ethics application status

Approved

Date submitted

28/03/2019

Date registered

23/04/2019

Date last updated

4/06/2019

Date data sharing statement initially provided

23/04/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

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

Scientific title

An open-label study to assess the efficacy and safety of LM011 in subjects diagnosed with Non-Alcoholic Steatohepatitis (NASH)

Secondary ID [1]

LM011-18-01

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Non-Alcoholic Steatohepatitis (NASH)

Condition category

Condition code

Metabolic and Endocrine

Metabolic disorders

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Percent change from Screening in liver fat fraction (%), measured by Magnetic Resonance Imaging-derived proton density fat fraction (MRI-PDFF).

MRI-PDFF data will be collected at screening visit and at end-of-study visit (Week 16) for all individual subjects. If there are subjects with missing Week-16 MRI-PDFF data due to drop out, regardless of reasons, two types of analyses will be performed. The first type of analysis will exclude the subject(s) who drop out, while the second type will include the drop-out subject(s) but will assume LM011 has no effect on “liver fat fraction” on these subject(s).

Timepoint [1]

16 weeks

Primary outcome [2]

Proportion of subjects with at least a 25% decrease in % steatosis

The percentage change is calculated by taking the difference between the baseline and Week 16 measurements and divide the difference by the baseline value . Similar to that described above for the analysis of the first Primary Endpoint, two types of analysis will also be performed. For subjects drop out early, the first type of analysis will exclude the subject(s) who drop out, while the second type of analysis will include all subject(s) and will assume LM011 had no effect on liver fat fraction on the subjects who drop out early.

At Screening and Week 16, MRI-PDFF over 9 regions of interest will provide estimates of liver fat fractions, measured in %. Based on this biomarker, % steatosis of the liver can be estimated.
The percentage change is calculated by taking the difference between the Screening and Week 16 measurements in % steatosis and divide the difference by the Screening % steatosis.
Proportion of subjects with at least 25% decrease will be summarized.

Timepoint [2]

16 weeks

Secondary outcome [1]

Change in liver fat fraction by MRI-PDFF

Timepoint [1]