Study of Safety and Efficacy of Tropifexor (LJN452) in Pa... | NCT02855164 | Trialant
NCT02855164
Sponsor
Novartis Pharmaceuticals
Status
Terminated
Last Update Posted
Sep 5, 2021Actual
Enrollment
350Actual
Phase
Phase 2
Conditions
Non-alcoholic Steatohepatitis (NASH)
Interventions
Tropifexor (LJN452)
Placebo
Countries
United States
Argentina
Australia
Austria
Belgium
Canada
France
Germany
India
Italy
Japan
Netherlands
Singapore
Slovakia
South Korea
Spain
Taiwan
Protocol Section
Identification Module
NCT ID
NCT02855164
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CLJN452A2202
Secondary IDs
ID
Type
Description
Link
2015-005215-33
EudraCT Number
Brief Title
Study of Safety and Efficacy of Tropifexor (LJN452) in Patients With Non-alcoholic Steatohepatitis (NASH)
Official 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
Acronym
FLIGHT-FXR
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Aug 2021
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Aug 1, 2016Actual
Primary Completion Date
Apr 6, 2020Actual
Completion Date
Apr 6, 2020Actual
First Submitted Date
Jul 20, 2016
First Submission Date that Met QC Criteria
Aug 1, 2016
First Posted Date
Aug 4, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 6, 2021
Results First Submitted that Met QC Criteria
Jul 7, 2021
Results First Posted Date
Jul 29, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Aug 11, 2021
Last Update Posted Date
Sep 5, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of the study was 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
Detailed Description
Part A In Part A, 77 subjects were randomized at baseline to receive tropifexor (10 μg, 30 μg, 60 μg or 90 μg) or placebo (Arms A, B, C, D and E) for 12 weeks. After ≥ 90% of the subjects from Part A completed 8 weeks of treatment, the first interim analysis of all Part A data was performed and the Data Monitoring Committee (DMC) recommended evaluation of 90 μg tropifexor (safe andefficacious) in Part B. The treatment arms of Part A were completed through Week 16 without adaptation.
Part B Randomization for Part B was started after the DMC recommendations on the dose to be used in Part B were implemented by the sponsor. As planned in the study protocol, since the first interim analysis selected one active dose (90 μg) to be tested in Part B, one of the other originally planned active treatment arms (60 μg) was included with a smaller sample size to confirm the earlier findings of this dose observed in Part A. Therefore, in Part B, 121 subjects, were randomized at baseline to receive tropifexor (90 μg and 60 μg) or placebo (Arms F, G and H) for 12 weeks.
Part C was introduced as a result of the DMC recommendation to pursue doses > 90 μg. Randomization in Part C started once the Part B randomization was completed. In Part C, 152 subjects were randomized at baseline to receive 140 μg or 200 μg tropifexor or placebo (Arms I, J and K) for 48 weeks.
One patient was treated at 2 sites but is still only one patient. 350 total enrollment, and not 351.
Conditions Module
Conditions
Non-alcoholic Steatohepatitis (NASH)
Keywords
LJN452
non-alcoholic steatohepatitis
NASH
phase 2
adaptive design
randomized
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
350Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
LJN452 10 μg
Experimental
Tropifexor (LJN452) Part A
Drug: Tropifexor (LJN452)
LJN452 30 μg
Experimental
Tropifexor (LJN452) Part A
Drug: Tropifexor (LJN452)
LJN452 60 μg
Experimental
Tropifezor (LJN452) Parts A + B
Drug: Tropifexor (LJN452)
LJN452 90 μg
Experimental
Tropifexor (LJN452) Parts A + B
Drug: Tropifexor (LJN452)
Placebo A+ B
Placebo Comparator
Placebo Parts A + B
Drug: Placebo
LJN452 140 μg
Experimental
Tropifexor (LJN452) Part C
Drug: Tropifexor (LJN452)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Tropifexor (LJN452)
Drug
Comparison of different doses of drug
LJN452 10 μg
LJN452 140 μg
LJN452 200 μg
LJN452 30 μg
LJN452 60 μg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Nonalcoholic Steatohepatitis (NASH) Patients With Treatment Emergent Adverse Events (TEAE)
Number of Nonalcoholic steatohepatitis (NASH) patients with TEAEs
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)
Change in Transaminase Levels (ALT)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. High levels of ALT may indicate liver damage. Normal range for ALT is typically 10 to 45 U/L or so (varies a little by age and gender). Elevation of these values indicate more liver inflammation/damage.
ALT elevation is not unexpected in this patient population
Dose relationship of tropifexor (LJN452) on ALT marker of hepatic inflammation in NASH from baseline to week 12
Summary statistics of change in ALT from baseline to EOT by treatment
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)
Change in Aspartate Transaminase (AST)
To determine the dose relationship of tropifexor (LJN452) on markers of hepatic inflammation (AST) in NASH from baseline to Week 12 The alanine aminotransferase (AST) test is a blood test that checks for liver damage. High levels of AST may indicate liver damage. Normal range for AST is typically 10 to 45 U/L or so (varies a little by age and gender). Elevation of these values indicate more liver inflammation/damage
AST elevation is not unexpected in this patient population
The aspartate aminotransferase (AST) test is a blood test that checks for liver damage. Higher levels indicate more possible liver damage
Summary statistics of change in AST from baseline up to end of treatment (EOT)
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)
Change From Baseline in % of Fat in the Liver Assessed Using Magnetic Resonance Imaging (MRI)
Repeated measures analysis: Relative change in percentage of fat in the liver assessed using MRI from baseline by visit up to EOT (Full analysis set)
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in Weight
Repeated measures for LS mean change in weight after 12 weeks of treatment
48 weeks
Change in Body Mass Index (BMI)
Repeated measures for the LS mean change in BMI after 12 weeks of treatment. Body mass index (BMI) is a measure of body fat based on height and weight
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
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
A Randomized, Patient and Investigator Blinded, Placebo Controlled, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of LMB763 in Patients With Non-alcoholic Steatohepatitis (NASH)
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.
In Part A, 77 were randomized at baseline to receive tropifexor 10 μg (n=14), 30μg (n=16), 60 μg (n=16) or 90 μg (n=15) or placebo (n=16)
In Part B, 121 were randomized at baseline to receive tropifexor 90 μg (n=70) and 60 μg (n=21) or placebo (n=30)
780 were screened in Part C. Of these 152 met eligibility criteria and were randomized to receive tropifexor 140 μg (n=50) or 200 μg (n=51) or placebo (n=51)
Recruitment Details
In total, 411 subjects were screened in Parts A and B of the study together. Of these, 198 subjects were deemed eligible to participate in the study and were subsequently randomized
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
FG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
Periods
Title
Milestones
Reasons Not Completed
Parts A + B (Randomized Set)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Oct 5, 2017
Apr 6, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose finding, 3-part (Parts A, B, and C), adaptive design study to assess the safety, tolerability, and efficacy of six doses of tropifexor as compared to placebo in subjects with NASH. Each study part had a screening period followed by a double-blind, randomized, treatment period, and a post-treatment follow-up period.
This study was extended based on safety and efficacy results in Part A and available long-term toxicology coverage; Part C was added to explore 48 weeks of treatment at higher doses with paired biopsies in F2/3 NASH patients.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantCare ProviderInvestigator
LJN452 200 μg
Experimental
Tropifexor (LJN452) Part B
Drug: Tropifexor (LJN452)
Placebo C
Placebo Comparator
Placebo Part C
Drug: Placebo
LJN452 90 μg
Placebo
Drug
Comparator
Placebo A+ B
Placebo C
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)
12 weeks
Change From Baseline in Waist to Hip (WTH) Ratio
The LS mean change in waist to hip ratio after 12 weeks of treatment
12 weeks
Change From Baseline in Biomarker FGF19
Dose-response relationship of tropifexor (LJN452) on FGF19 over time, a marker of FXR target engagement in the gut.
ANCOVA: Ratio of FGF19 (pg/mL) post-dose to pre-dose at Week 6
Value at 6 weeks minus value at baseline
baseline, week 6
Change From Baseline in Biomarker C4
Dose-response relationship of LJN452 on C4, a marker of hepatic target engagement at 4 hours post dose
C4 (ng/mL): Summary statistics by treatment and visit
Week 6, 4 hours post dose
Change From Baseline on Markers of Liver Fibrosis, Fibroscan
Dose-response relationship of tropifexor (LJN452) on markers of liver fibrosis commonly available such as Fibroscan®
Liver stiffness (kPa): Summary statistics by treatment and visit
FibroScan is a specialized ultrasound machine for measuring fibrosis (scarring) in the liver
Scores range from 0-4 with zero being no liver scarring and 4 being advanced liver scarring (cirrhosis)
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
Change From Baseline on Markers of Liver Fibrosis Panel (ELF) Score
ANCOVA: LS Mean Change in Enhanced liver fibrosis panel (ELF) score from baseline by visit up to EOT.
The total ELF score reference range calculated non-parametrically is 6.72 (90% CI 6.58-6.84) to 9.79 (90% CI 9.45-10.01); Journal of Hepatology 2013 vol. 59 j 236-242.
Enhanced liver fibrosis Test (ELF) panel: the following was assessed: hyaluronic acid (HA), tissue inhibitor of metalloproteinases (TIMP-1), and amino-terminal pro-peptide of procollagen type III (PIIINP).
The Enhanced Liver Fibrosis score is a linear combination of TIMP-1, PIIINP, and HA with the following formula: ELF score = 2.494+0.846 x ln(HA) + 0.735 x ln (PIIINP) + 0.391 x ln (TIMP-1).
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
Change From Baseline on Markers of Liver Fibrosis, Fibrotest (Parts A+B)
Fibrosis biomarker test, originally called Fibrotest®/ Fibrosure®, is combines α2-macroglobulin (a2m), apolipoprotein A1 (aA1), total bilirubin (BIL), haptoglobin (h), GGT, and ALT. The coefficient for the score is calculated as: z = 4.467 x log(a2m) - 1.357 x log(h) + 1.017 x log(GGT) + 0.0281 x Age + 1.737 x log(BIL) - 1.184 x (aA1) + 0.301 x Gender - 5.54 where Gender = 1 for male and Gender = 0 for female. The score is then: 1/(1+e^-z).
Calculated scores range from 0.00 (no fibrosis) to 1.00 (severe fibrosis or cirrhosis) (See Part C in separate outcomes that follows)
End of Treatment (EoT):12 weeks
Change From Baseline on Markers of Liver Fibrosis, Fibrotest, (Part C)
Fibrosis biomarker test, originally called Fibrotest®/ Fibrosure®, is combines α2-macroglobulin (a2m), apolipoprotein A1 (aA1), total bilirubin (BIL), haptoglobin (h), GGT, and ALT. The coefficient for the score is calculated as: z = 4.467 x log(a2m) - 1.357 x log(h) + 1.017 x log(GGT) + 0.0281 x Age + 1.737 x log(BIL) - 1.184 x (aA1) + 0.301 x Gender - 5.54 where Gender = 1 for male and Gender = 0 for female. The score is then: 1/(1+e^-z).
Calculated scores range from 0.00 (no fibrosis) to 1.00 (severe fibrosis or cirrhosis)
End of Treatment (EoT) was 48 weeks
Change From Baseline on Gamma-glutamyl Transferase (GGT)
Summary statistics of change in GGT (IU/L) from baseline by visit up to EoT
EoT for Parts A+B=12 weeks; EoT for Part C = 48 weeks
Change From Baseline on Fasting Lipid Profile
Repeated measures analysis: LS geometric mean ratio of fasting lipids to baseline by visit up to EOT
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
Itch Based on a Visual Analog Scale (VAS) Rating Scale
Repeated measures analysis: Change in VAS for Itch from baseline by visit up to EoT
VAS score 0 = no disease; and 9 is severely advanced disease
EoT for Parts A+B=12 weeks; EoT for Part C = 48 weeks
Pre-dose Trough Concentration (Ctrough) of LJN452
Pre-dose Trough Concentration (Ctrough) of tropifexor (LJN452)
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
C2h (Steady-state Drug Levels 2 Hours Postdose) of LJN452
Summary C2h of tropifexor (LJN452)
Days 7 and 14 (10 and 30μg LJN452 C2h was not measured day 14)
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
Number of patients who have at least one point improvement in fibrosis (NASH CRN staging) without worsening of steatohepatitis (total score)
EoT (Week 48)
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening - FDA
Number of patients who have at least one point improvement in fibrosis (NASH CRN staging) without worsening of steatohepatitis (FDA)
EoT (Week 48)
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening - EMA
Number of patients who have at least one point improvement in fibrosis (NASH CRN staging) without worsening of steatohepatitis (EMA)
EoT (Week 48)
Biopsy-based Response at Week 48 Compared to Baseline: Difference Between Treatment Groups (Part C) - Resolution of Steatohepatitis (Diagnostic Category)
Resolution of steatohepatitis (diagnostic category) without worsening of fibrosis (NASH CRN staging)
EoT (Week 48)
Biopsy-based Response at Week 48 Compared to Baseline: Difference Between Treatment Groups (Part C) - Resolution of Steatohepatitis (FDA, EMA)
Resolution of steatohepatitis (diagnostic category) without worsening of fibrosis (NASH CRN staging)
EoT (Week 48)
North Little Rock
Arkansas
72117
United States
Novartis Investigative Site
Coronado
California
92118
United States
Novartis Investigative Site
Los Angeles
California
90057
United States
Novartis Investigative Site
Pasadena
California
91105
United States
Novartis Investigative Site
Rialto
California
92377
United States
Novartis Investigative Site
San Diego
California
92114
United States
Novartis Investigative Site
San Francisco
California
94115
United States
Novartis Investigative Site
Lonetree
Colorado
80124
United States
Novartis Investigative Site
Boca Raton
Florida
33434
United States
Novartis Investigative Site
Jacksonville
Florida
32256
United States
Novartis Investigative Site
Lakewood Rch
Florida
34211
United States
Novartis Investigative Site
Miami
Florida
33136
United States
Novartis Investigative Site
Orlando
Florida
32806
United States
Novartis Investigative Site
Pensacola
Florida
32503
United States
Novartis Investigative Site
Athens
Georgia
30607
United States
Novartis Investigative Site
Marietta
Georgia
30060
United States
Novartis Investigative Site
Catonsville
Maryland
21228
United States
Novartis Investigative Site
Worcester
Massachusetts
01655
United States
Novartis Investigative Site
Detroit
Michigan
48202
United States
Novartis Investigative Site
Minneapolis
Minnesota
55455
United States
Novartis Investigative Site
Jefferson City
Missouri
65109
United States
Novartis Investigative Site
Berlin
New Jersey
08009
United States
Novartis Investigative Site
Morehead City
North Carolina
28557
United States
Novartis Investigative Site
Cincinnati
Ohio
45219
United States
Novartis Investigative Site
Hermitage
Tennessee
37076
United States
Novartis Investigative Site
Dallas
Texas
75208-2312
United States
Novartis Investigative Site
Houston
Texas
77030
United States
Novartis Investigative Site
San Antonio
Texas
78215
United States
Novartis Investigative Site
Norfolk
Virginia
23502
United States
Novartis Investigative Site
Richmond
Virginia
23298
United States
Novartis Investigative Site
CABA
Buenos Aires
C1181ACH
Argentina
Novartis Investigative Site
Caba
Buenos Aires
C1280AEB
Argentina
Novartis Investigative Site
Buenos Aires
C1120AAC
Argentina
Novartis Investigative Site
Kingswood
New South Wales
2747
Australia
Novartis Investigative Site
Fitzroy
Victoria
3065
Australia
Novartis Investigative Site
Salzburg
5020
Austria
Novartis Investigative Site
Vienna
1090
Austria
Novartis Investigative Site
Brussels
1070
Belgium
Novartis Investigative Site
Ghent
9000
Belgium
Novartis Investigative Site
Leuven
3000
Belgium
Novartis Investigative Site
London
Ontario
N6A 5A5
Canada
Novartis Investigative Site
Toronto
Ontario
M5G 2C4
Canada
Novartis Investigative Site
Chicoutimi
Quebec
G7H 7K9
Canada
Novartis Investigative Site
Montpellier
34295
France
Novartis Investigative Site
Paris
75012
France
Novartis Investigative Site
Paris
75651
France
Novartis Investigative Site
Dresden
01307
Germany
Novartis Investigative Site
Hamburg
20246
Germany
Novartis Investigative Site
Hanover
30625
Germany
Novartis Investigative Site
Leipzig
04103
Germany
Novartis Investigative Site
Würzburg
97080
Germany
Novartis Investigative Site
New Delhi
National Capital Territory of Delhi
110070
India
Novartis Investigative Site
Bergamo
BG
24128
Italy
Novartis Investigative Site
Bologna
40138
Italy
Novartis Investigative Site
Roma
00161
Italy
Novartis Investigative Site
Hatsukaichi
Hiroshima
738 8503
Japan
Novartis Investigative Site
Yokohama
Kanagawa
236-0004
Japan
Novartis Investigative Site
Saga
Saga-ken
849-8501
Japan
Novartis Investigative Site
Izumo
Shimane
693 8501
Japan
Novartis Investigative Site
Utrecht
3584CX
Netherlands
Novartis Investigative Site
Singapore
169608
Singapore
Novartis Investigative Site
Banská Bystrica
97517
Slovakia
Novartis Investigative Site
Bratislava
82606
Slovakia
Novartis Investigative Site
Bratislava
85101
Slovakia
Novartis Investigative Site
Nitra
949 01
Slovakia
Novartis Investigative Site
Seoul
Korea
03722
South Korea
Novartis Investigative Site
Seoul
Korea
05505
South Korea
Novartis Investigative Site
Dongjak Gu
Seoul
07061
South Korea
Novartis Investigative Site
Busan
602739
South Korea
Novartis Investigative Site
Seoul
03080
South Korea
Novartis Investigative Site
Seville
Andalusia
41013
Spain
Novartis Investigative Site
Barcelona
Catalonia
08035
Spain
Novartis Investigative Site
Barcelona
Catalonia
08036
Spain
Novartis Investigative Site
Madrid
28009
Spain
Novartis Investigative Site
Madrid
28034
Spain
Novartis Investigative Site
Kaoshiung
Taiwan
80756
Taiwan
Novartis Investigative Site
Keelung
20401
Taiwan
Novartis Investigative Site
Taichung
40447
Taiwan
Novartis Investigative Site
Taipei
11217
Taiwan
Novartis Investigative Site
Taoyuan
33305
Taiwan
Derived
Naoumov NV, Brees D, Loeffler J, Chng E, Ren Y, Lopez P, Tai D, Lamle S, Sanyal AJ. Digital pathology with artificial intelligence analyses provides greater insights into treatment-induced fibrosis regression in NASH. J Hepatol. 2022 Nov;77(5):1399-1409. doi: 10.1016/j.jhep.2022.06.018. Epub 2022 Jun 30.
FG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A+B)
FG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
FG004
Placebo A+B
Placebo A+B
FG005
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
FG006
LJN452 200 μg
200 micrograms of Tropifexor (Part C)
FG007
Placebo C
Placebo (Part C)
FG00014 subjects
FG00116 subjects
FG00237 subjects
FG00385 subjects
FG00446 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
COMPLETED
FG00014 subjects
FG00116 subjects
FG00236 subjects
FG00377 subjects
FG00445 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0038 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0032 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0034 subjects
FG004
Part C (Randomized Set)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG00550 subjects
FG00651 subjects
FG00751 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Full analysis set (FAS) was all subjects to whom study treatment had been assigned. Following the intent-to-treat (ITT) principle, subjects were analyzed according to the treatment they have been assigned to at randomization.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
BG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
BG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A+B)
BG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
BG004
Placebo A+B
Placebo (Parts A+B)
BG005
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
BG006
LJN452 200 μg
200 micrograms of Tropifexor (Part C)
BG007
Placebo C
Placebo (Part C)
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00014
BG00116
BG00237
BG00385
BG00446
BG00550
BG00651
BG00751
BG008350
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
FAS
Count of Participants
Participants
No
Title
Denominators
Categories
Parts A + B
ParticipantsBG00014
ParticipantsBG00116
ParticipantsBG00237
ParticipantsBG003
Age, Continuous
Full Analysis Set
Mean
Standard Deviation
years
Title
Denominators
Categories
Parts A + B
ParticipantsBG00014
ParticipantsBG00116
ParticipantsBG002
Sex: Female, Male
Sex of participant by treatment
FAS
Count of Participants
Participants
Title
Denominators
Categories
Parts A + B
ParticipantsBG00014
ParticipantsBG00116
ParticipantsBG002
Race/Ethnicity, Customized
FAS
Count of Participants
Participants
No
Title
Denominators
Categories
Caucasian (Parts A + B)
ParticipantsBG00014
ParticipantsBG00116
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Nonalcoholic Steatohepatitis (NASH) Patients With Treatment Emergent Adverse Events (TEAE)
Number of Nonalcoholic steatohepatitis (NASH) patients with TEAEs
Safety analysis set (SAS) is all subjects who received at least one dose of drug and had at least one post-baseline safety assessment.
Posted
Count of Participants
Participants
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)
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A+B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A+B)
OG004
Placebo A+B
Placebo (Parts A+B)
OG005
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG006
LNJ452 200 μg
200 micrograms of Tropifexor (Part C)
OG007
Placebo Part C
Placebo (Part C)
Units
Counts
Participants
OG00013
OG00117
OG00237
OG003
Title
Denominators
Categories
Title
Measurements
OG0005
OG00111
OG00224
OG003
Primary
Change in Transaminase Levels (ALT)
The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. High levels of ALT may indicate liver damage. Normal range for ALT is typically 10 to 45 U/L or so (varies a little by age and gender). Elevation of these values indicate more liver inflammation/damage.
ALT elevation is not unexpected in this patient population
Dose relationship of tropifexor (LJN452) on ALT marker of hepatic inflammation in NASH from baseline to week 12
Summary statistics of change in ALT from baseline to EOT by treatment
Full analysis set (FAS): All subjects to whom study treatment had been assigned.
Following the intent-to-treat (ITT) principle, subjects were analyzed according to the treatment they have been assigned to at randomization.
Posted
Mean
Standard Deviation
IU/L
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)
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
Primary
Change in Aspartate Transaminase (AST)
To determine the dose relationship of tropifexor (LJN452) on markers of hepatic inflammation (AST) in NASH from baseline to Week 12 The alanine aminotransferase (AST) test is a blood test that checks for liver damage. High levels of AST may indicate liver damage. Normal range for AST is typically 10 to 45 U/L or so (varies a little by age and gender). Elevation of these values indicate more liver inflammation/damage
AST elevation is not unexpected in this patient population
The aspartate aminotransferase (AST) test is a blood test that checks for liver damage. Higher levels indicate more possible liver damage
Summary statistics of change in AST from baseline up to end of treatment (EOT)
Full Analysis Set (FAS)
Posted
Mean
Standard Deviation
U/L
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)
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
Primary
Change From Baseline in % of Fat in the Liver Assessed Using Magnetic Resonance Imaging (MRI)
Repeated measures analysis: Relative change in percentage of fat in the liver assessed using MRI from baseline by visit up to EOT (Full analysis set)
FAS
Posted
Mean
Standard Error
percentage of fat in the liver
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)
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Secondary
Change From Baseline in Weight
Repeated measures for LS mean change in weight after 12 weeks of treatment
FAS
Posted
Mean
Standard Error
kg
48 weeks
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A) vs placebo
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
OG005
LJN452 140 μg
Secondary
Change in Body Mass Index (BMI)
Repeated measures for the LS mean change in BMI after 12 weeks of treatment. Body mass index (BMI) is a measure of body fat based on height and weight
FAS
Posted
Mean
Standard Error
kg/m2
12 weeks
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
OG005
Secondary
Change From Baseline in Waist to Hip (WTH) Ratio
The LS mean change in waist to hip ratio after 12 weeks of treatment
FAS
Posted
Mean
Standard Error
ratio
12 weeks
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
OG005
LJN452 140 μg
Secondary
Change From Baseline in Biomarker FGF19
Dose-response relationship of tropifexor (LJN452) on FGF19 over time, a marker of FXR target engagement in the gut.
ANCOVA: Ratio of FGF19 (pg/mL) post-dose to pre-dose at Week 6
Value at 6 weeks minus value at baseline
FAS
Posted
Geometric Least Squares Mean
95% Confidence Interval
pg/mL
baseline, week 6
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
Secondary
Change From Baseline in Biomarker C4
Dose-response relationship of LJN452 on C4, a marker of hepatic target engagement at 4 hours post dose
C4 (ng/mL): Summary statistics by treatment and visit
FAS
Posted
Mean
Standard Deviation
ng/mL
Week 6, 4 hours post dose
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
OG005
Secondary
Change From Baseline on Markers of Liver Fibrosis, Fibroscan
Dose-response relationship of tropifexor (LJN452) on markers of liver fibrosis commonly available such as Fibroscan®
Liver stiffness (kPa): Summary statistics by treatment and visit
FibroScan is a specialized ultrasound machine for measuring fibrosis (scarring) in the liver
Scores range from 0-4 with zero being no liver scarring and 4 being advanced liver scarring (cirrhosis)
FAS
Posted
Mean
Standard Deviation
scores
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Secondary
Change From Baseline on Markers of Liver Fibrosis Panel (ELF) Score
ANCOVA: LS Mean Change in Enhanced liver fibrosis panel (ELF) score from baseline by visit up to EOT.
The total ELF score reference range calculated non-parametrically is 6.72 (90% CI 6.58-6.84) to 9.79 (90% CI 9.45-10.01); Journal of Hepatology 2013 vol. 59 j 236-242.
Enhanced liver fibrosis Test (ELF) panel: the following was assessed: hyaluronic acid (HA), tissue inhibitor of metalloproteinases (TIMP-1), and amino-terminal pro-peptide of procollagen type III (PIIINP).
The Enhanced Liver Fibrosis score is a linear combination of TIMP-1, PIIINP, and HA with the following formula: ELF score = 2.494+0.846 x ln(HA) + 0.735 x ln (PIIINP) + 0.391 x ln (TIMP-1).
FAS
Posted
Least Squares Mean
Standard Error
scores on a scale
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Parts A + B)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
Secondary
Change From Baseline on Markers of Liver Fibrosis, Fibrotest (Parts A+B)
Fibrosis biomarker test, originally called Fibrotest®/ Fibrosure®, is combines α2-macroglobulin (a2m), apolipoprotein A1 (aA1), total bilirubin (BIL), haptoglobin (h), GGT, and ALT. The coefficient for the score is calculated as: z = 4.467 x log(a2m) - 1.357 x log(h) + 1.017 x log(GGT) + 0.0281 x Age + 1.737 x log(BIL) - 1.184 x (aA1) + 0.301 x Gender - 5.54 where Gender = 1 for male and Gender = 0 for female. The score is then: 1/(1+e^-z).
Calculated scores range from 0.00 (no fibrosis) to 1.00 (severe fibrosis or cirrhosis) (See Part C in separate outcomes that follows)
FAS
Posted
Mean
Standard Deviation
scores
End of Treatment (EoT):12 weeks
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
Secondary
Change From Baseline on Markers of Liver Fibrosis, Fibrotest, (Part C)
Fibrosis biomarker test, originally called Fibrotest®/ Fibrosure®, is combines α2-macroglobulin (a2m), apolipoprotein A1 (aA1), total bilirubin (BIL), haptoglobin (h), GGT, and ALT. The coefficient for the score is calculated as: z = 4.467 x log(a2m) - 1.357 x log(h) + 1.017 x log(GGT) + 0.0281 x Age + 1.737 x log(BIL) - 1.184 x (aA1) + 0.301 x Gender - 5.54 where Gender = 1 for male and Gender = 0 for female. The score is then: 1/(1+e^-z).
Calculated scores range from 0.00 (no fibrosis) to 1.00 (severe fibrosis or cirrhosis)
FAS
Posted
Least Squares Mean
Standard Error
scores
End of Treatment (EoT) was 48 weeks
ID
Title
Description
OG000
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG001
LJN452 200 μg
200 micrograms of Tropifexor (Part C)
OG002
Placebo A+B
Placebo A+B
Units
Counts
Secondary
Change From Baseline on Gamma-glutamyl Transferase (GGT)
Summary statistics of change in GGT (IU/L) from baseline by visit up to EoT
FAS
Posted
Least Squares Mean
Standard Error
IU/L
EoT for Parts A+B=12 weeks; EoT for Part C = 48 weeks
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
OG005
Secondary
Change From Baseline on Fasting Lipid Profile
Repeated measures analysis: LS geometric mean ratio of fasting lipids to baseline by visit up to EOT
FAS
Posted
Geometric Least Squares Mean
95% Confidence Interval
mmol/L
End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo (Parts A+B)
Secondary
Itch Based on a Visual Analog Scale (VAS) Rating Scale
Repeated measures analysis: Change in VAS for Itch from baseline by visit up to EoT
VAS score 0 = no disease; and 9 is severely advanced disease
FAS
Posted
Least Squares Mean
Standard Error
scores
EoT for Parts A+B=12 weeks; EoT for Part C = 48 weeks
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Part A)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A) vs placebo
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B) vs placebo
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
Placebo A+B
Placebo for parts A + B
Secondary
Pre-dose Trough Concentration (Ctrough) of LJN452
Pre-dose Trough Concentration (Ctrough) of tropifexor (LJN452)
FAS
Posted
Mean
Standard Deviation
ng/mL
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
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Parts A + B)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Parts A + B)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
OG004
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
Secondary
C2h (Steady-state Drug Levels 2 Hours Postdose) of LJN452
Summary C2h of tropifexor (LJN452)
FAS
Posted
Mean
Standard Deviation
ng/mL
Days 7 and 14 (10 and 30μg LJN452 C2h was not measured day 14)
ID
Title
Description
OG000
LJN452 10 μg
10 micrograms of Tropifexor (Parts A + B)
OG001
LJN452 30 μg
30 micrograms of Tropifexor (Parts A + B)
OG002
LJN452 60 μg
60 micrograms of Tropifexor (Parts A + B)
OG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
Units
Counts
Participants
Secondary
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
Number of patients who have at least one point improvement in fibrosis (NASH CRN staging) without worsening of steatohepatitis (total score)
Full analysis set (FAS)
Posted
Count of Participants
Participants
EoT (Week 48)
ID
Title
Description
OG000
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG001
LNJ452 200 μg
200 micrograms of Tropifexor (Part C)
OG002
Placebo C
Placebo (Part C)
Units
Counts
Participants
OG000
Secondary
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening - FDA
Number of patients who have at least one point improvement in fibrosis (NASH CRN staging) without worsening of steatohepatitis (FDA)
Full analysis set (FAS)
Posted
Count of Participants
Participants
EoT (Week 48)
ID
Title
Description
OG000
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG001
LNJ452 200 μg
200 micrograms of Tropifexor (Part C)
OG002
Placebo A+B
Placebo A+B
Units
Counts
Participants
OG000
Secondary
Biopsy-based Response at Week 48 Compared to Baseline: At Least One Point Improvement in Fibrosis (NASH CRN Staging) Without Worsening - EMA
Number of patients who have at least one point improvement in fibrosis (NASH CRN staging) without worsening of steatohepatitis (EMA)
Full analysis set (FAS)
Posted
Count of Participants
Participants
EoT (Week 48)
ID
Title
Description
OG000
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG001
LNJ452 200 μg
200 micrograms of Tropifexor (Part C)
OG002
Placebo A+B
Placebo A+B
Units
Counts
Participants
OG000
Secondary
Biopsy-based Response at Week 48 Compared to Baseline: Difference Between Treatment Groups (Part C) - Resolution of Steatohepatitis (Diagnostic Category)
Resolution of steatohepatitis (diagnostic category) without worsening of fibrosis (NASH CRN staging)
Full analysis set (FAS)
Posted
Count of Participants
Participants
EoT (Week 48)
ID
Title
Description
OG000
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG001
LNJ452 200 μg
200 micrograms of Tropifexor (Part C)
OG002
Placebo A+B
Placebo A+B
Units
Counts
Participants
OG000
Secondary
Biopsy-based Response at Week 48 Compared to Baseline: Difference Between Treatment Groups (Part C) - Resolution of Steatohepatitis (FDA, EMA)
Resolution of steatohepatitis (diagnostic category) without worsening of fibrosis (NASH CRN staging)
Full analysis set (FAS)
Posted
Count of Participants
Participants
EoT (Week 48)
ID
Title
Description
OG000
LJN452 140 μg
140 micrograms of Tropifexor (Part C)
OG001
LNJ452 200 μg
200 micrograms of Tropifexor (Part C)
OG002
Placebo A+B
Placebo A+B
Units
Counts
Participants
OG000
Time Frame
To End of Treatment (EoT): For Parts A&B, EoT was Week 12; For Part C, EoT was Week 48
Description
AEs are any untoward sign or symptom that occurred during the study treatment period
350 patients were randomized. One patient was treated at 2 sites, so 351 enrolled may appearr in some places.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
LJN452 10 μg
LJN452 10 mcg (Part A)
0
13
0
13
5
13
EG001
LJN452 30 μg
30 micrograms of Tropifexor (Part A)
0
17
0
17
11
17
EG002
LJN452 60 μg
LJN452 60 mcg (Parts A+B)
0
37
0
37
16
37
EG003
LJN452 90 μg
90 micrograms of Tropifexor (Parts A + B)
0
85
4
85
50
85
EG004
LJN452 140 μg
LJN452 140 mcg (Part C)
0
50
5
50
43
50
EG005
LJN452 200 μg
LJN452 200 mcg (Part C)
0
51
3
51
45
51
EG006
Placebo
Placebo A+B+C
0
97
6
97
63
97
EG007
Total
Total
0
350
18
350
233
350
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Angina pectoris
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG0030 affected85 at risk
EG0041 affected50 at risk
EG0051 affected51 at risk
EG0060 affected97 at risk
EG0072 affected350 at risk
Tachycardia
Cardiac disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Animal bite
Injury, poisoning and procedural complications
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Multiple injuries
Injury, poisoning and procedural complications
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Synovial cyst
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Trigger finger
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Device dislocation
Product Issues
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Renal impairment
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Endometrial thickening
Reproductive system and breast disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Haemothorax
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG0030 affected85 at risk
EG0041 affected50 at risk
EG0050 affected51 at risk
EG0061 affected97 at risk
EG0073 affected350 at risk
Abdominal distension
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0021 affected37 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected17 at risk
EG0020 affected37 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0021 affected37 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0021 affected37 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0021 affected37 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0021 affected37 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected17 at risk
EG0020 affected37 at risk
EG003
Fatigue
General disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0013 affected17 at risk
EG0021 affected37 at risk
EG003
Pyrexia
General disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Body tinea
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Influenza
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Laryngitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0022 affected37 at risk
EG003
Periodontitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0022 affected37 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Viral sinusitis
Infections and infestations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Blood creatinine increased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Platelet count decreased
Investigations
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0012 affected17 at risk
EG0021 affected37 at risk
EG003
Diabetes mellitus
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Headache
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected17 at risk
EG0021 affected37 at risk
EG003
Poor quality sleep
Nervous system disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0021 affected37 at risk
EG003
Loss of libido
Psychiatric disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected17 at risk
EG0021 affected37 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0013 affected17 at risk
EG0021 affected37 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0011 affected17 at risk
EG0020 affected37 at risk
EG003
Neurodermatitis
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0001 affected13 at risk
EG0010 affected17 at risk
EG0020 affected37 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0025 affected37 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0021 affected37 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA (20.1)
Systematic Assessment
EG0000 affected13 at risk
EG0010 affected17 at risk
EG0022 affected37 at risk
EG003
No outputs were planned; and are not available for determining the effects of tropifexor on primary endpoints in the subset of patients who had historical biopsy data.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.