Clinical trial NCT04147195: Study of Various Treatments in Non-alcoholic Fatty Liver Disease (NAFLD) Patients Who Have Aspects of Non-alcoholic Steatohepatitis (NASH)
Official title: NASH EXploratory Single and COmbination Treatment (NEXSCOT): An Open Label, Multicenter, Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Various Single and Combination Treatments in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) Who Manifest a Non-alcoholic Steatohepatitis (NASH)-Like Biomarker Phenotype
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-alcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Keywords: Non-alcoholic fatty liver disease
NAFLD
Non-alcoholic steatohepatitis
NASH
Platform design
LYS006
LJN452
Tropifexor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-11-01
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in adult patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype.

Detailed description: This was a Phase II, non-confirmatory, multicenter, open label, platform study in NAFLD participants with a NASH-like biomarker phenotype to examine the effects of single and combination therapies over 12 weeks of treatment. The study consisted of four distinct study periods:

* Screening Period (Day -60 to -28): Lasted up to a maximum of 33 days where participants were assessed for inclusion and exclusion criteria prior the baseline assessments.
* Baseline Period (Day -27 to -1): Lasted up to a maximum of 27 days and comprised baseline assessments and randomization.
* Treatment Period (Day 1 to 85): Participants were randomized in a 1:1 ratio to LYS006 20 mg (twice a day) arm or to LYS006 20 mg (twice a day) and tropifexor 200ug (once a day). Participants were treated daily during 12 weeks.
* Follow-up Period (Day 85 to 113): After completion of the treatment period, participants were observed until the End Of Study (EOS) visit at Day 113.

Eligibility criteria: Inclusion Criteria:

Phenotypic diagnosis of NASH based on the presence of all of the following:

* ALT ≥ 43 IU/L (males) or ≥ 28 IU/L (females)
* BMI ≥ 27 kg/m2 (race other than Asian) or ≥ 23 kg/m2 (Asian race)
* History of type 2 diabetes mellitus with HbA1c ≤ 9%
* ELF test score ≥ 8.5 and ≤ 10.5
* Liver fat ≥ 8%
* Patients must weigh between 40 kg (88 lbs.) and 150 kg (330 lbs.)

Exclusion Criteria:

* Use of other investigational drugs within 5 half-lives of randomization or within 3 months, whichever is longer
* Use of obeticholic acid (OCA) or pharmacologically-active weight loss drugs within 1 month of randomization
* Use of strong CYP3A4/5 inhibitors or strong CYP3A4 inducers within 5 half-lives or 7 days of randomization, whichever is longer
* History or presence of other concomitant liver diseases
* History or current diagnosis of ECG abnormalities
* Patients with contraindications to MRI imaging
* Current or history of significant alcohol consumption
* Clinical evidence of hepatic decompensation or severe liver impairment
* Women of child bearing potential (unless on highly effective methods of contraception)
* Presence of liver cirrhosis
* Use of OAT3 inhibitors within 5 half-lives or 7 days of randomization, whichever is longer

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 113 Days
Secondary outcomes:
measure: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score
timeFrame: Baseline and Days 57, 85 and EOS (Day 113)
measure: Change From Baseline in Cholesterol: Fasting Lipid Profile Endpoint
timeFrame: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)
measure: Change From Baseline in Percent Liver Fat at Day 85
timeFrame: Baseline and Day 85
measure: Change From Baseline in Total Body Weight
timeFrame: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)
measure: Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Day 85
timeFrame: Baseline and Day 85
measure: Change From Baseline in Fasting Glucose
timeFrame: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)
measure: Change From Baseline in Fasting Insulin at Day 85
timeFrame: Baseline and Day 85
measure: Change From Baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)
measure: Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: Baseline and days 15, 29, 43, 57, 85 and EOS (Day 113)
measure: Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline and Days 57, 85 and EOS (Day 113)
measure: LYS006 Plasma Concentration
timeFrame: pre-dose at Days 1, 29, 57 and 85 and post-dose (1, 2, 3 and 4 hours) at Days 29 and 57
measure: Maximum Observed Plasma Concentration (Cmax) of LYS006
timeFrame: pre-dose and post-dose (1, 2, 3 and 4 hours) at Days 29 and 57
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Miami Lakes
country: United States
facility: Novartis Investigative Site
state: Florida
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Honolulu
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: South Bend
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Morehead City
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
state: Nordrhine Westphalia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: