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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02855164
Ethics application status
Date submitted
20/07/2016
Date registered
4/08/2016

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: LJN452 10 µg - Tropifexor (LJN452) Part A

Experimental: LJN452 30 µg - Tropifexor (LJN452) Part A

Experimental: LJN452 60 µg - Tropifezor (LJN452) Parts A + B

Experimental: LJN452 90 µg - Tropifexor (LJN452) Parts A + B

Placebo comparator: Placebo A+ B - Placebo Parts A + B

Experimental: LJN452 140 µg - Tropifexor (LJN452) Part C

Experimental: LJN452 200 µg - Tropifexor (LJN452) Part B

Placebo comparator: Placebo C - Placebo Part C


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 Nonalcoholic Steatohepatitis (NASH) Patients With Treatment Emergent Adverse Events (TEAE)
Timepoint [1] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12 (Primary Outcome Measure). For Part C, EoT was Week 48 (Secondary Outcome Measure)
Primary outcome [2] 0 0
Change in Transaminase Levels (ALT)
Timepoint [2] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12 (Primary Outcome Measure). For Part C, EoT was Week 48 (Secondary Outcome Measure)
Primary outcome [3] 0 0
Change in Aspartate Transaminase (AST)
Timepoint [3] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12 (Primary Outcome Measure). For Part C, EoT was Week 48 (Secondary Outcome Measure)
Primary outcome [4] 0 0
Change From Baseline in % of Fat in the Liver Assessed Using Magnetic Resonance Imaging (MRI)
Timepoint [4] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12 (Primary Outcome Measure). For Part C, EoT was Week 48 (Secondary Outcome Measure)
Secondary outcome [1] 0 0
Change From Baseline in Weight
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
Change in Body Mass Index (BMI)
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Change From Baseline in Waist to Hip (WTH) Ratio
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Change From Baseline in Biomarker FGF19
Timepoint [4] 0 0
baseline, week 6
Secondary outcome [5] 0 0
Change From Baseline in Biomarker C4
Timepoint [5] 0 0
Week 6, 4 hours post dose
Secondary outcome [6] 0 0
Change From Baseline on Markers of Liver Fibrosis, Fibroscan
Timepoint [6] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
Secondary outcome [7] 0 0
Change From Baseline on Markers of Liver Fibrosis Panel (ELF) Score
Timepoint [7] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
Secondary outcome [8] 0 0
Change From Baseline on Markers of Liver Fibrosis, Fibrotest (Parts A+B)
Timepoint [8] 0 0
End of Treatment (EoT):12 weeks
Secondary outcome [9] 0 0
Change From Baseline on Markers of Liver Fibrosis, Fibrotest, (Part C)
Timepoint [9] 0 0
End of Treatment (EoT) was 48 weeks
Secondary outcome [10] 0 0
Change From Baseline on Gamma-glutamyl Transferase (GGT)
Timepoint [10] 0 0
EoT for Parts A+B=12 weeks; EoT for Part C = 48 weeks
Secondary outcome [11] 0 0
Change From Baseline on Fasting Lipid Profile
Timepoint [11] 0 0
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
Secondary outcome [12] 0 0
Itch Based on a Visual Analog Scale (VAS) Rating Scale
Timepoint [12] 0 0
EoT for Parts A+B=12 weeks; EoT for Part C = 48 weeks
Secondary outcome [13] 0 0
Pre-dose Trough Concentration (Ctrough) of LJN452
Timepoint [13] 0 0
In Parts A and B, LJN452 Ctrough was measured on Study Days 7, 14, 28, 42, 56, and 84. In Part C LJN452 Ctrough was measured on Study Days 42, 84, 168, 280 and 336
Secondary outcome [14] 0 0
C2h (Steady-state Drug Levels 2 Hours Postdose) of LJN452
Timepoint [14] 0 0
Days 7 and 14 (10 and 30µg LJN452 C2h was not measured day 14)
Secondary outcome [15] 0 0
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening of Steatohepatitis (Part C) - Total Score
Timepoint [15] 0 0
EoT (Week 48)
Secondary outcome [16] 0 0
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening - FDA
Timepoint [16] 0 0
EoT (Week 48)
Secondary outcome [17] 0 0
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening - EMA
Timepoint [17] 0 0
EoT (Week 48)
Secondary outcome [18] 0 0
Biopsy-based Response at Week 48 Compared to Baseline: Difference Between Treatment Groups (Part C) - Resolution of Steatohepatitis (Diagnostic Category)
Timepoint [18] 0 0
EoT (Week 48)
Secondary outcome [19] 0 0
Biopsy-based Response at Week 48 Compared to Baseline: Difference Between Treatment Groups (Part C) - Resolution of Steatohepatitis (FDA, EMA)
Timepoint [19] 0 0
EoT (Week 48)

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
Sex
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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/04/2020
Sample size
Target
Accrual to date
Final
350
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
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
Argentina
State/province [18] 0 0
Buenos Aires
Country [19] 0 0
Austria
State/province [19] 0 0
Salzburg
Country [20] 0 0
Austria
State/province [20] 0 0
Wien
Country [21] 0 0
Belgium
State/province [21] 0 0
Bruxelles
Country [22] 0 0
Belgium
State/province [22] 0 0
Gent
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
France
State/province [26] 0 0
Montpellier
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
Germany
State/province [28] 0 0
Dresden
Country [29] 0 0
Germany
State/province [29] 0 0
Hamburg
Country [30] 0 0
Germany
State/province [30] 0 0
Hannover
Country [31] 0 0
Germany
State/province [31] 0 0
Leipzig
Country [32] 0 0
Germany
State/province [32] 0 0
Wuerzburg
Country [33] 0 0
India
State/province [33] 0 0
Delhi
Country [34] 0 0
Italy
State/province [34] 0 0
BG
Country [35] 0 0
Italy
State/province [35] 0 0
Bologna
Country [36] 0 0
Italy
State/province [36] 0 0
Roma
Country [37] 0 0
Japan
State/province [37] 0 0
Hiroshima
Country [38] 0 0
Japan
State/province [38] 0 0
Kanagawa
Country [39] 0 0
Japan
State/province [39] 0 0
Saga
Country [40] 0 0
Japan
State/province [40] 0 0
Shimane
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Korea
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Seoul
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Busan
Country [44] 0 0
Netherlands
State/province [44] 0 0
Utrecht
Country [45] 0 0
Singapore
State/province [45] 0 0
Singapore
Country [46] 0 0
Slovakia
State/province [46] 0 0
Banska Bystrica
Country [47] 0 0
Slovakia
State/province [47] 0 0
Bratislava
Country [48] 0 0
Slovakia
State/province [48] 0 0
Nitra
Country [49] 0 0
Spain
State/province [49] 0 0
Andalucia
Country [50] 0 0
Spain
State/province [50] 0 0
Cataluna
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Taiwan
State/province [52] 0 0
Kaoshiung
Country [53] 0 0
Taiwan
State/province [53] 0 0
Keelung City
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taichung
Country [55] 0 0
Taiwan
State/province [55] 0 0
Taipei
Country [56] 0 0
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02855164