non-alcoholic steatohepatitis (NASH) MedDRA version: 20.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Code: LMB763
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not established
CAS Number: Not assigned
Other descriptive name: LMB763
Concentration unit: mg milligram(s)
Concentration t
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort 1 - Male and female patients 18 years or older (at the time of the screening visit) - Presence of NASH as demonstrated by ONE of the following: EITHER: 1) Histologic evidence of NASH based on liver biopsy obtained 2 years or less before randomization with a diagnosis consistent with NASH, fibrosis level F1, F2 or F3, in the absence of a histological diagnosis of alternative chronic liver diseases AND ALT = 60 IU/L (males) or = 40 IU/L (females) OR 2) Phenotypic diagnosis of NASH based on the presence of ALL THREE of the following: - ALT = 60 IU/L (males) or = 40 IU/L (females) AND - BMI = 27 kg/m2 (in patients with a self-identified race other than Asian) or =23 kg/m2 (in patients with a self-identified Asian race) AND - Diagnosis of Type 2 diabetes mellitus by having either: HbA1C = 6.5% OR Symptoms of diabetes plus hyperglycemia as indicated by fasting plasma glucose =126 mg/dl (= 7.0 mmol/l), two hour plasma glucose concentration =200mg/dl (=11.1 mmol/l, two hours after 75g anhydrous glucose in an oral glucose tolerance test (OGTT) OR Drug therapy for Type 2 diabetes mellitus Cohort 2 - Male and female patients 18 years or older (at the time of the screening visit) - Liver fat = 10% at baseline as determined by the reading of the central MRI laboratory of locally produced images - Presence of NASH as demonstrated by ONE of the following: EITHER 3. Histologic evidence of NASH based on liver biopsy obtained 2 years or less before randomization with a diagnosis consistent with NASH, fibrosis level F1, F2 or F3, in the absence of a histological diagnosis of alternative chronic liver diseases AND ALT = 43IU/L (males) or = 28 IU/L (females) OR 4. Phenotypic diagnosis of NASH based on the presence of ALL THREE of the following: - ALT = 43 IU/L (males) or = 28 IU/L (females) AND - BMI = 27 kg/m2 (in patients with a self-identified race other than Asian) or =23 kg/m2 (in patients with a self-identified Asian race) AND - Diagnosis of Type 2 diabetes mellitus by having either: - HbA1C = 6.5% OR - Symptoms of diabetes plus hyperglycemia as indicated by - fasting plasma glucose =126 mg/dl (= 7.0 mmol/l) - two hour plasma glucose concentration = 200mg/dl (= 11.1 mmol/l two hours after 75g anhydrous glucose in an oral glucose tolerance test (OGTT) OR - Drug therapy for Type 2 diabetes mellitus Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 144 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: Cohort 1 and 2 - Current use of obeticholic acid (OCA) - New initiation of GLP-1 agonists such as liraglutide, exenatide , lixisenatide, albiglutide or dulaglutide within 3 months of screening - Patients on treatment with the following medicines UNLESS they are on a stable dose (± 25% of current dose) for at least 1 month before randomization: anti-diabetic medications, insulin (if =25% change in dose), beta-blockers, thiazide diuretics, fibrates, statins, niacin, ezetimibe, vitamin E (if doses > 200 IU/day; doses > 800 IU/day are prohibited), thyroid hormone, psychotropic medications, estrogen or estrogen containing birth control. For oral anti-diabetic medications, no more than one step up in local prescribing guidelines will be allowed. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 5 days (approximately 5 times the terminal half life) after stopping study medication - Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening (significant alcohol consumption is defined as more than 20 g/day in females and more than 30 g/day in males, on average) and/or a score on the AUDIT questionnaire =8 as administered by the site as part of the medical history - History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and baseline. Marijuana use is not allowed if it is determined to be medically inappropriate by the investigator - Calculated eGFR less than 60 mL/min (using the MDRD formula) - Presence of cirrhosis on liver biopsy or clinical diagnosis - Clinical evidence of hepatic decompensation or severe liver impairment - History or presence of other concomitant liver diseases - History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study - Patients with contraindications to MRI imaging - For those patients that have had a previous biopsy: Significant weight loss (>15%) or change in clinical status (in the opinion of the investigator) since the diagnostic liver biopsy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To determine the safety and tolerability of LMB763 during 12 weeks of treatment - To determine the effect of LMB763 on circulating alanine aminotransferase (ALT) levels ;Secondary Objective: - To evaluate the pharmacokinetics (PK) of LMB763 in NASH patients - To determine the effect of LMB763 on intrahepatic lipid after 12 weeks of treatment - To determine the effect of LMB763 on anthropometric assessments after 12 weeks of treatment - To determine the effect of LMB763 on non-invasive markers of liver fibrosis - To determine the effect of LMB763 on fasting lipid profile - To determine the effect of LMB763 compared with placebo with respect to occurrence and impact of potential itch ;Primary end point(s): Change from baseline in ALT;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy / Pharmacodynamics - Pharmacokinetics - Pharmacokinetic / pharmacodynamic interactions ;Timepoint(s) of evaluation of this end point: From baseline to 12 weeks | — |
Countries
Australia, China, Georgia, Jordan, New Zealand, Switzerland, United Kingdom, United States
Contacts
Public ContactMedical Information Services
Novartis Pharmaceuticals UK Limited
Outcome results
None listed