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

Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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

ClinicalTrials.gov ID

NCT02855164

Acronym / sponsor ID

FLIGHT-FXR / CLJN452A2202

Conditions

Non-alcoholic Steatohepatitis (NASH)

Keywords

LJN452, non-alcoholic steatohepatitis, NASH, phase 2, adaptive design, randomized

Phase

Phase 2

Study type

Interventional

Recruitment status

Terminated

Enrolment

350 participants (actual)

Lead sponsor

Novartis PharmaceuticalsIndustry (pharma, biotech, devices)

Study start

1 Aug 2016 (actual)

Primary completion

6 Apr 2020 (actual)

Study completion

6 Apr 2020 (actual)

First posted

4 Aug 2016 (estimated)

Results

Posted 29 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Triple blind (participant, care provider, investigator)

Number of arms

8

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.

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Nonalcoholic Steatohepatitis (NASH) Patients With Treatment Emergent Adverse Events (TEAE)

   Time frame: 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

2. Change in Transaminase Levels (ALT)

   Time frame: 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

3. Change in Aspartate Transaminase (AST)

   Time frame: 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 possible liver damage Summary statistics of change in AST from baseline up to end of treatment (EOT)

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

   Time frame: 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)

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 36797481Sanyal AJ, Lopez P, Lawitz EJ, Lucas KJ, Loeffler J, Kim W, Goh GBB, Huang JF, Serra C, Andreone P, Chen YC, Hsia SH, Ratziu V, Aizenberg D, Tobita H, Sheikh AM, Vierling JM, Kim YJ, Hyogo H, Tai D, Goodman Z, Schaefer F, Carbarns IRI, Lamle S, Martic M, Naoumov NV, Brass CA. Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial. Nat Med. 2023 Feb;29(2):392-400. doi: 10.1038/s41591-022-02200-8. Epub 2023 Feb 16.
• Derived from this study: PubMed 35779659Naoumov 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.
• 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)Link provided by the sponsor.
• Individual participant dataSharing planned: Undecided. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

81 sites in 17 countries: see every site and its status.