Study of safety, tolerability and efficacy of a combination treatment of tropifexor (LJN452) & licogliflozin (LIK066) compared to each monotherapy, compared with placebo in adult participants with nonalcoholic steatohepatitis (NASH) and liver fibrosis

A randomized, double-blind, parallel-group, multicenter study to assess efficacy, safety, and tolerability of oral tropifexor (LJN452) & licogliflozin (LIK066) combination therapy, compared to each monotherapy, compared with placebo for treatment of adult participants with nonalcoholic steatohepatitis (NASH) and liver fibrosis (ELIVATE)

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-002324-32-BE

Enrollment

380

Registered

2019-10-22

Start date

2019-12-13

Completion date

Unknown

Last updated

2022-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-alcoholic Steatohepatitis (NASH) MedDRA version: 24.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders

Interventions

Product Name: Tropifexor Product Code: LJN452 Pharmaceutical Form: Capsule, hard INN or Proposed INN: TROPIFEXOR Current Sponsor code: LJN452 Concentration unit: mg milligram(s) Concentration type: eq

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Presence of NASH with fibrosis as confirmed by central reader's evaluation of liver biopsy obtained no more than 6 months before randomization. demonstrated by the following: - NASH using NAFLD Activity Score (NAS) >= 4 with at least 1 point each in inflammation and ballooning and - Fibrosis stage 2 or 3 using NASH CRN fibrosis criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 325 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55

Exclusion criteria

Exclusion criteria: •Type 1 diabetes mellitus •Uncontrolled type 2 diabetes defined as glycated hemoglobin (HbA1c) = 9% at screening •HbA1c ULN ?ALT or AST > 5xULN (in either of the 2 values) ?Total bilirubin > ULN (see central lab manual) (including Gilbert's syndrome) ?Alkaline phosphatase > 300 IU/L (in either of the 2 values during screening) ?History of esophageal varices, ascites or hepatic encephalopathy ?Splenomegaly ?MELD >12

Design outcomes

Primary

Measure	Time frame
Secondary Objective: To evaluate the efficacy of combination therapy and two monotherapies in NASH or fibrosis with a composite endpoint after 48 weeks of treatment To evaluate improvement in fibrosis by at least one stage after 48 weeks of treatment To evaluate improvement in fibrosis by at least two stages with no worsening of NASH after 48 weeks of treatment To evaluate reduction in body weight from Baseline after 48 weeks of treatment To evaluate change in liver fat content after 48 weeks of treatment To evaluate the relationship of investigational treatment and markers of hepatic inflammation in NASH (ALT and AST) after 48 weeks of treatment To evaluate the relationship of investigational treatment and GGT, a marker of cholestasis and oxidative stress after 48 weeks of treatment To evaluate the safety and tolerability of tropifexor (LJN452) in combination with licogliflozin (LIK066), and each monotherapy treatment, compared to placebo, after 48 weeks of treatment;Main Objective: The primary objective of the study is to evaluate the efficacy of tropifexor + licogliflozin in combination therapy and each monotherapy treatment, as assessed by histologic improvement after 48 weeks compared to placebo in participants with NASH and stage 2 or 3 fibrosis.;Primary end point(s): - Whether the participant has at least a one point improvement in fibrosis without worsening of steatohepatitis at Week 48 compared to baseline - Whether the participant achieves resolution of steatohepatitis without worsening of fibrosis at Week 48 compared to baseline;Timepoint(s) of evaluation of this end point: 48 weeks	—

Measure

Time frame

Secondary Objective: To evaluate the efficacy of combination therapy and two monotherapies in NASH or fibrosis with a composite endpoint after 48 weeks of treatment To evaluate improvement in fibrosis by at least one stage after 48 weeks of treatment To evaluate improvement in fibrosis by at least two stages with no worsening of NASH after 48 weeks of treatment To evaluate reduction in body weight from Baseline after 48 weeks of treatment To evaluate change in liver fat content after 48 weeks of treatment To evaluate the relationship of investigational treatment and markers of hepatic inflammation in NASH (ALT and AST) after 48 weeks of treatment To evaluate the relationship of investigational treatment and GGT, a marker of cholestasis and oxidative stress after 48 weeks of treatment To evaluate the safety and tolerability of tropifexor (LJN452) in combination with licogliflozin (LIK066), and each monotherapy treatment, compared to placebo, after 48 weeks of treatment;Main Objective: The primary objective of the study is to evaluate the efficacy of tropifexor + licogliflozin in combination therapy and each monotherapy treatment, as assessed by histologic improvement after 48 weeks compared to placebo in participants with NASH and stage 2 or 3 fibrosis.;Primary end point(s): - Whether the participant has at least a one point improvement in fibrosis without worsening of steatohepatitis at Week 48 compared to baseline - Whether the participant achieves resolution of steatohepatitis without worsening of fibrosis at Week 48 compared to baseline;Timepoint(s) of evaluation of this end point: 48 weeks

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Secondary

Measure	Time frame
Secondary end point(s): •Whether the participant achieves resolution of NASH and no worsening of fibrosis OR improvement in fibrosis by at least one stage without worsening of NASH at Week 48 compared with baseline. •Whether the participant has at least one stage improvement in fibrosis at Week 48 compared with baseline •Whether the participant has at least two stage improvement in fibrosis without worsening of NASH at Week 48 compared with baseline •Whether the participant has 5% or more reduction in body weight at Week 48 compared to baseline •Change in liver fat content based on MRI - PDFF (in 40% of participants) over time up to Week 48 compared with baseline •Change in ALT and AST over time up to Week 48 compared with baseline To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH (ALT and AST) •Change in GGT over time up to Week 48 compared with baseline To determine the relationship of investigational treatment and GGT, a marker of cholestasis and oxidative stress •Number of participants with adverse events To evaluate the safety and tolerability of tropifexor (LJN452) in combination with licogliflozin (LIK066), and each monotherapy treatment compared to placebo after 48 weeks of treatment.;Timepoint(s) of evaluation of this end point: 48 weeks	—

Measure

Time frame

Secondary end point(s): •Whether the participant achieves resolution of NASH and no worsening of fibrosis OR improvement in fibrosis by at least one stage without worsening of NASH at Week 48 compared with baseline. •Whether the participant has at least one stage improvement in fibrosis at Week 48 compared with baseline •Whether the participant has at least two stage improvement in fibrosis without worsening of NASH at Week 48 compared with baseline •Whether the participant has 5% or more reduction in body weight at Week 48 compared to baseline •Change in liver fat content based on MRI - PDFF (in 40% of participants) over time up to Week 48 compared with baseline •Change in ALT and AST over time up to Week 48 compared with baseline To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH (ALT and AST) •Change in GGT over time up to Week 48 compared with baseline To determine the relationship of investigational treatment and GGT, a marker of cholestasis and oxidative stress •Number of participants with adverse events To evaluate the safety and tolerability of tropifexor (LJN452) in combination with licogliflozin (LIK066), and each monotherapy treatment compared to placebo after 48 weeks of treatment.;Timepoint(s) of evaluation of this end point: 48 weeks

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Countries

Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Denmark, Egypt, Estonia, France, Germany, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Portugal, Russian Federation, Saudi Arabia, Singapore, Slovakia, South Africa, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

Public ContactClinical Trial Information Desk

Novartis Pharma AG

clinicaltrial.enquiries@novartis.com+4161324 1111

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026