NCT02855164 (FLIGHT-FXR) is a Phase 2 clinical trial of Tropifexor (LJN452) in Non-alcoholic Steatohepatitis (NASH), sponsored by Novartis Pharmaceuticals.

Who is sponsoring NCT02855164?

NCT02855164 is sponsored by Novartis Pharmaceuticals.

What drugs are being tested in NCT02855164?

Interventions in NCT02855164: Tropifexor (LJN452), Placebo.

What condition does NCT02855164 study?

NCT02855164 studies Non-alcoholic Steatohepatitis (NASH).

Is NCT02855164 still recruiting?

NCT02855164 is currently terminated. Last updated 5 September 2021.

Are results published for NCT02855164?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2021-09-05 · How we verify

NCT02855164: FLIGHT-FXR

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Study of Safety and Efficacy of Tropifexor (LJN452) in Patients With Non-alcoholic Steatohepatitis (NASH)

Terminated Phase 2 Results posted Last updated 5 September 2021

What this trial tests

Phase 2 trial testing Tropifexor (LJN452) in Non-alcoholic Steatohepatitis (NASH) in 350 participants. Terminated before completion.

Timeline

1 August 2016

Primary endpoint
6 April 2020

6 April 2020

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	350
Start date	1 August 2016
Primary completion	6 April 2020
Estimated completion	6 April 2020
Sites	81 locations across France, Italy, Japan, Netherlands, Slovakia, Belgium, Austria, Taiwan

Drugs / interventions tested

Tropifexor (LJN452) — full drug profile →
Placebo

Conditions studied

Non-alcoholic Steatohepatitis (NASH) — all drugs for Non-alcoholic Steatohepatitis (NASH) →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Non-alcoholic Steatohepatitis (NASH). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Nonalcoholic Steatohepatitis (NASH) Patients With Treatment Emergent Adverse Events (TEAE) Primary · 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)

Number of Nonalcoholic steatohepatitis (NASH) patients with TEAEs

Group	Value	95% CI
LJN452 10 μg	5
LJN452 30 μg	11
LJN452 60 μg	24
LJN452 90 μg	61
Placebo A+B	31
LJN452 140 μg	49
LNJ452 200 μg	49
Placebo Part C	46

Change in Transaminase Levels (ALT) Primary · 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)

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

Group	Value	95% CI
LJN452 10 μg	-16.7	± 17.53
LJN452 30 μg	-12.0	± 35.99
LJN452 60 μg	-17.3	± 28.12
LJN452 90 μg	-15.4	± 30.32
Placebo A+B	-8.1	± 29.37
LJN452 140 μg	-27.0	± 30.24
LNJ452 200 μg	-28.7	± 25.40
Placebo Part C	-11.7	± 61.64

Change in Aspartate Transaminase (AST) Primary · 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)

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 pos

Group	Value	95% CI
LJN452 10 μg	-11.3	± 12.09
LJN452 30 μg	-2.1	± 29.62
LJN452 60 μg	-10.2	± 25.03
LJN452 90 μg	-2.5	± 24.60
Placebo A+B	-7.1	± 23.85
LJN452 140 μg	-16.7	± 23.36
LJN452 200 μg	-13.3	± 20.14
Placebo Part C	-13.1	± 29.00

Change From Baseline in % of Fat in the Liver Assessed Using Magnetic Resonance Imaging (MRI) Primary · 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)

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)

Group	Value	95% CI
LJN452 10 μg	-7.48	± 6.174
LJN452 30 μg	-14.07	± 5.661
LJN452 60 μg	-15.04	± 3.754
LJN452 90 μg	-12.34	± 2.482
Placebo A+B	-6.19	± 3.381
LJN452 140 μg	-31.25	± 5.228
LJN452 200 μg	-39.54	± 4.968
Placebo Part C	-3.58	± 4.718

Change From Baseline in Weight Secondary · 48 weeks

Repeated measures for LS mean change in weight after 12 weeks of treatment

Group	Value	95% CI
LJN452 10 μg	-1.79	± 0.608
LJN452 30 μg	-0.78	± 0.567
LJN452 60 μg	-1.05	± 0.377
LJN452 90 μg	-1.15	± 0.253
Placebo A+B	0.00	± 0.338
LJN452 140 μg	-5.10	± 0.988
LJN452 200 μg	-5.89	± 1.002
Placebo Part C	-2.48	± 0.915

Change in Body Mass Index (BMI) Secondary · 12 weeks

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

Group	Value	95% CI
LJN452 10 μg	-0.64	± 0.208
LJN452 30 μg	-0.29	± 0.194
LJN452 60 μg	-0.35	± 0.129
LJN452 90 μg	-0.42	± 0.087
Placebo A+B	0.02	± 0.116
LJN452 140 μg	-1.88	± 0.322
LJN452 200 μg	-2.11	± 0.327
Placebo Part C	-0.80	± 0.299

Change From Baseline in Waist to Hip (WTH) Ratio Secondary · 12 weeks

The LS mean change in waist to hip ratio after 12 weeks of treatment

Group	Value	95% CI
LJN452 10 μg	-0.01	± 0.009
LJN452 30 μg	0.00	± 0.008
LJN452 60 μg	-0.01	± 0.005
LJN452 90 μg	0.00	± 0.004
Placebo A+B	0.00	± 0.005
LJN452 140 μg	0.00	± 0.008
LJN452 200 μg	-0.01	± 0.007
Placebo Part C	-0.02	± 0.007

Change From Baseline in Biomarker FGF19 Secondary · baseline, week 6

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

Group	Value	95% CI
LJN452 10 μg	1.45	0.93 – 2.26
LJN452 30 μg	1.53	1.00 – 2.35
LJN452 60 μg	3.82	2.88 – 5.09
LJN452 90 μg	5.78	4.78 – 6.98
Placebo A+B	1.33	1.03 – 1.73
LJN452 140 μg	1.97	1.48 – 2.62
LJN452 200 μg	2.23	1.65 – 3.01
Placebo Part C	1.22	0.92 – 1.61

Change From Baseline in Biomarker C4 Secondary · Week 6, 4 hours post dose

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

Group	Value	95% CI
LJN452 10 μg	38.82	± 25.765
LJN452 30 μg	32.75	± 23.360
LJN452 60 μg	28.38	± 13.394
LJN452 90 μg	40.19	± 31.356
Placebo A+B	47.70	± 25.524
LJN452 140 μg	14.97	± 20.232
LJN452 200 μg	8.54	± 9.583
Placebo Part C	38.40	± 24.552

Change From Baseline on Markers of Liver Fibrosis, Fibroscan Secondary · End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48

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)

Group	Value	95% CI
LJN452 10 μg	10.94	± 5.314
LJN452 30 μg	10.40	± 7.663
LJN452 60 μg	9.90	± 4.095
LJN452 90 μg	9.00	± 4.152
Placebo A+B	9.30	± 4.676
LJN452 140 μg	11.29	± 3.677
LJN452 200 μg	12.03	± 4.804
Placebo (Part C)	11.26	± 4.027

Change From Baseline on Markers of Liver Fibrosis Panel (ELF) Score Secondary · End of Treatment (EoT): For Parts A&B, EoT was Week 12. For Part C, EoT was Week 48

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

Group	Value	95% CI
LJN452 10 μg	0.05	± 0.158
LJN452 30 μg	0.00	± 0.146
LJN452 60 μg	-0.19	± 0.097
LJN452 90 μg	0.20	± 0.064
Placebo A+B	0.08	± 0.087
LJN452 140 μg	-0.34	± 0.132
LJN452 200 μg	-0.24	± 0.122
Placebo Part C	-0.08	± 0.115

Change From Baseline on Markers of Liver Fibrosis, Fibrotest (Parts A+B) Secondary · End of Treatment (EoT):12 weeks

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)

Group	Value	95% CI
LJN452 10 μg	-0.23	± 0.284
LJN452 30 μg	-1.49	± 0.852
LJN452 60 μg	-1.44	± 1.080
LJN452 90 μg	-1.34	± 1.222
Placebo (A+B)	-1.23	± 1.088

Adverse events — posted to ClinicalTrials.gov

Time frame: To End of Treatment (EoT): For Parts A&B, EoT was Week 12; For Part C, EoT was Week 48. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LJN452 10 μg

Serious: 0/13 (0%)

Deaths: 0/13

LJN452 30 μg

Serious: 0/17 (0%)

Deaths: 0/17

LJN452 60 μg

Serious: 0/37 (0%)

Deaths: 0/37

LJN452 90 μg

Serious: 4/85 (5%)

Deaths: 0/85

LJN452 140 μg

Serious: 5/50 (10%)

Deaths: 0/50

LJN452 200 μg

Serious: 3/51 (6%)

Deaths: 0/51

Placebo

Serious: 6/97 (6%)

Deaths: 0/97

Total

Serious: 18/350 (5%)

Deaths: 0/350

Serious adverse events (20 terms)

Reaction	System	LJN452 10 μg	LJN452 30 μg	LJN452 60 μg	LJN452 90 μg	LJN452 140 μg	LJN452 200 μg	Placebo	Total
Angina pectoris	Cardiac disorders	—	—	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—	—	—
Haematochezia	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—
Animal bite	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Multiple injuries	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Synovial cyst	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Trigger finger	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—	—	—	—	—	—
Device dislocation	Product Issues	—	—	—	—	—	—	—	—
Nephrolithiasis	Renal and urinary disorders	—	—	—	—	—	—	—	—
Renal impairment	Renal and urinary disorders	—	—	—	—	—	—	—	—
Endometrial thickening	Reproductive system and breast disorders	—	—	—	—	—	—	—	—
Haemothorax	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—

Other adverse events (52 terms — click to expand)

Reaction	System	LJN452 10 μg	LJN452 30 μg	LJN452 60 μg	LJN452 90 μg	LJN452 140 μg	LJN452 200 μg	Placebo	Total
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Rash pruritic	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Body tinea	Infections and infestations	—	—	—	—	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—

Most-reported serious reactions: Angina pectoris, Tachycardia, Haematochezia, Non-cardiac chest pain, Cholecystitis acute, Gastroenteritis, Animal bite, Multiple injuries.

Data from ClinicalTrials.gov NCT02855164 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Mechanisms of NAFLD development and therapeutic strategies.
Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. · · 2018 · cited 3203× · PMID 29967350 · DOI 10.1038/s41591-018-0104-9
Current and future pharmacological therapies for NAFLD/NASH.
Sumida Y, Yoneda M. · · 2018 · cited 487× · PMID 29247356 · DOI 10.1007/s00535-017-1415-1
Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.
Fleishman JS, Kumar S. · · 2024 · cited 267× · PMID 38664391 · DOI 10.1038/s41392-024-01811-6
Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).
Xu X, Poulsen KL, Wu L, Liu S, et al · · 2022 · cited 235× · PMID 35963848 · DOI 10.1038/s41392-022-01119-3
Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases.
Gutiérrez-Cuevas J, Santos A, Armendariz-Borunda J. · · 2021 · cited 173× · PMID 34769060 · DOI 10.3390/ijms222111629
Gut liver brain axis in diseases: the implications for therapeutic interventions.
Yan M, Man S, Sun B, Ma L, et al · · 2023 · cited 165× · PMID 38057297 · DOI 10.1038/s41392-023-01673-4
Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.
Wu X, Xu M, Geng M, Chen S, et al · · 2023 · cited 161× · PMID 37244925 · DOI 10.1038/s41392-023-01439-y
Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges.
Dufour JF, Caussy C, Loomba R. · · 2020 · cited 145× · PMID 32381514 · DOI 10.1136/gutjnl-2019-319104

Verify or expand the search:

Other trials of Tropifexor (LJN452)

Trials testing the same drug.

NCT03517540 — Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and · Phase 2 · completed

Other recruiting trials for Non-alcoholic Steatohepatitis (NASH)

Currently open trials in the same condition.

NCT05384652 — Simultaneous Quantification of Liver Fat Content, Fatty Acid Composition, and Fibrosis Using Spin-lock MRI for Steatohep · active not recruiting
NCT04820036 — A Physiologic Analysis of Endoscopic Sleeve Gastroplasty (ESG) · NA · active not recruiting
NCT02754037 — Non-alcoholic Fatty Liver Disease Parametric PET (FLiPP) Study · active not recruiting

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

NCT07498335 — Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary · Phase 3 · not yet recruiting
NCT07489573 — Study of Efficacy and Safety of Secukinumab in Chinese Adult Patients With Moderate to Severe Hidradenitis Suppurativa · Phase 4 · not yet recruiting
NCT07484269 — PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan · not yet recruiting
NCT07416162 — A Study of Iptacopan in Korean Patients With Paroxysmal Nocturnal Hemoglobinuria or C3 Glomerulopathy · not yet recruiting
NCT07387926 — Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+ · Phase 1, PHASE2 · not yet recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02855164 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Novartis Pharmaceuticals
Last refreshed: 5 September 2021

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02855164.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing