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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02855164




Registration number
NCT02855164
Ethics application status
Date submitted
20/07/2016
Date registered
4/08/2016
Date last updated
2/02/2021

Titles & IDs
Public title
Study of Safety and Efficacy of Tropifexor (LJN452) in Patients With Non-alcoholic Steatohepatitis (NASH)
Scientific title
A Randomized, Double-blind, Placebo Controlled, 3- Part, Adaptive Design, Multicenter Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Non-alcoholic Steatohepatitis (NASH): FLIGHT-FXR
Secondary ID [1] 0 0
2015-005215-33
Secondary ID [2] 0 0
CLJN452A2202
Universal Trial Number (UTN)
Trial acronym
FLIGHT-FXR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-alcoholic Steatohepatitis (NASH) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tropifexor (LJN452)
Treatment: Drugs - Placebo

Experimental: Part A - Arm A - Tropifexor (LJN452)- - dose 1

Experimental: Part A - Arm B - Tropifexor (LJN452)- - dose 2

Experimental: Part A - Arm C - Tropifezor (LJN452)- - dose 3

Experimental: Part A - Arm D - Tropifexor (LJN452)- - dose 4

Placebo Comparator: Part A - Arm E - Placebo

Experimental: Part B - Arm F - Tropifexor (LJN452)- - dose to be determined

Experimental: Part B - Arm G - Tropifexor (LJN452)- - dose to be determined

Placebo Comparator: Part B - Arm H - Placebo

Experimental: Part C- Arm I - Tropifexor (LJN452)- dose 9

Experimental: Part C- Arm J - Tropifexor (LJN452)- dose 10

Placebo Comparator: Part C- Arm K - Placebo


Treatment: Drugs: Tropifexor (LJN452)
Comparison of different doses of drug

Treatment: Drugs: Placebo
Comparator

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of NASH patients with Adverse events - Occurrence of Serious Adverse Event (SAE), Adverse Event (AE) resulting in treatment discontinuation and/or dose reductions, and AE of special interest, from baseline to week 12
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Change in Transaminase levels - To determine the dose relationship of tropifexor (LJN452) on markers of hepatic inflammation in NASH (ALT and AST) from baseline to Week 12.
Timepoint [2] 0 0
12 weeks
Primary outcome [3] 0 0
Change from baseline in % of fat in the liver assessed using Magnetic resonance imaging (MRI) - To determine the dose-response relationship of tropifexor (LJN452) on liver fat content by changes in quantitative MRI determined fat from baseline to Week 12.
Timepoint [3] 0 0
12 weeks
Secondary outcome [1] 0 0
Change from baseline in weight - To determine the effect of different doses of tropifexor (LJN452) on weight, after 12 weeks of treatment
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Change from baseline in biomarker FGF19 - To determine the dose-response relationship of tropifexor (LJN452) on FGF19 over time, a marker of FXR target engagement in the gut.
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Change from baseline on on markers of liver fibrosis - To determine the dose-response relationship of tropifexor (LJN452) on markers of liver fibrosis commonly available such as Fibroscan®, enhanced liver fibrosis panel (ELF), and fibrosis biomarker test (originally known as Fibrotest®/FibroSure®)
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Change from baseline on gamma-glutamyl transferase (GGT) - To determine the dose-response relationship of tropifexor (LJN452) on GGT, a marker of cholestasis
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Change from baseline on fasting lipid profile - To determine the effect of tropifexor (LJN452) on fasting lipid profile
Timepoint [5] 0 0
12 weeks
Secondary outcome [6] 0 0
Determine Ctrough of LJN452 - To determine the ctrough of tropifexor (LJN452)
Timepoint [6] 0 0
12 weeks
Secondary outcome [7] 0 0
Itch based on a visual analog scale (VAS) rating scale - The score (distance from left) on the VAS will be recorded by the patient marking with a line. The distance marked will be converted to a score between 0 and 10
Timepoint [7] 0 0
12 weeks
Secondary outcome [8] 0 0
Change from baseline in body mass index (BMI) - To determine the effect of different doses of tropifexor (LJN452) on BMI, after 12 weeks of treatment
Timepoint [8] 0 0
12 weeks
Secondary outcome [9] 0 0
Change from baseline in waist-to-hip (WTH) ratio - To determine the effect of different doses of tropifexor (LJN452) on waist-to-hip (WTH) ratio after 12 weeks of treatment
Timepoint [9] 0 0
12 weeks
Secondary outcome [10] 0 0
Change from baseline in biomarker C4 - To determine the dose-response relationship of LJN452 on C4, a marker of hepatic target engagement.
Timepoint [10] 0 0
12 weeks
Secondary outcome [11] 0 0
Determine C2h of LJN452 - To determine the pharmacokinetics (PK) of LJN452.
Timepoint [11] 0 0
12 weeks
Secondary outcome [12] 0 0
Effects on above mentioned primary outcome measures in a subset of patients with history of biopsy data - To determine the dose-response relationship of tropifexor (LJN452) in a subset of patients with historical biopsy data (both overall and by subsets defined by fibrosis score and/or NAS score) on the following primary outcome measures: adverse event profile; change in transaminase levels; on liver fat content by changes in quantitative MRI
Timepoint [12] 0 0
12 weeks

Eligibility
Key inclusion criteria
- male/female patients, 18 years or older

- written informed consent

- Part A and B patients : presence of NASH by histological evidence (liver biopsy
obtained 2 years or less prior to randomization) with fibrosis level of F1, F2 or F3
(fibrosis in the absence of cirrhosis) and no diagnosis of chronic liver disease and
elevated alanine aminotransferase (ALT) OR phenotypic diagnosis based on elevated ALT,
BMI and diagnosis of Type 2 diabetes mellitus (DM)

- Part C patients: presence of NASH by histological evidence (liver biopsy obtained
during the Screening period or 6 months or less prior to randomization) with fibrosis
level of F2 or F3 and no diagnosis of chronic liver disease

And ( All Parts):

- ALT = 43 IU/L (males) or = 28 IU/L (females)

- Liver fat equal to or higher than 10% by MRI
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- previous exposure to OCA

- patients taking prohibited medications

- patients taking the following medicines UNLESS on a stable dose (within 25% of
baseline dose) for at least 1 month before randomization: (for Part C patients, dose
must be stable for at least 1 month prior to biopsy through Screening : anti- diabetic
medications, insulin, 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

- pregnant or nursing (lactating) women

- current or history of significant alcohol consumption for a period of more than 3
consecutive months within 1 year prior to screening

- uncontrolled diabetes mellitus

- new use of GLP-1 agonists such as liraglutide, exenatide, lixisenatide, albiglutide or
dulaglutide within 3 months of screening

- presence of cirrhosis

- hepatic decompensation or severe liver impairment

- previous diagnosis of other forms of chronic liver disease

- patients with contraindications to MRI imaging

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kingswood
Recruitment hospital [2] 0 0
Novartis Investigative Site - Fitzroy
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
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Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
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Michigan
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United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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New Jersey
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Austria
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Salzburg
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Austria
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Wien
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Belgium
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Bruxelles
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Belgium
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Gent
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Belgium
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Leuven
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Canada
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Ontario
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Canada
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Quebec
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France
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Montpellier
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France
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Paris
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Germany
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Dresden
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Leipzig
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Germany
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Wuerzburg
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India
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Delhi
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Italy
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BG
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Italy
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Bologna
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Italy
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Roma
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Japan
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Hiroshima
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Japan
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Kanagawa
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Japan
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Saga
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Japan
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Shimane
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Korea, Republic of
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Korea
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Korea, Republic of
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Seoul
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Korea, Republic of
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Busan
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Netherlands
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Utrecht
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Singapore
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Singapore
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Slovakia
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Banska Bystrica
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Slovakia
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Bratislava
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Slovakia
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Nitra
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Spain
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Andalucia
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Spain
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Cataluna
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Spain
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Madrid
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Taiwan
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Kaoshiung
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Taiwan
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Keelung City
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
State/province [56] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the study is to assess the effects of different doses of tropifexor (LJN452)
with respect to safety, tolerability, and on markers of liver inflammation in patients with
NASH
Trial website
https://clinicaltrials.gov/show/NCT02855164
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications