Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (ELIVATE)

A Randomized, Double-blind, Parallel-group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Oral Tropifexor (LJN452) & Licogliflozin (LIK066) Combination Therapy and Each Monotherapy, Compared With Placebo for Treatment of Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis.(ELIVATE)

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

Study Overview

• Status: Terminated
• Conditions: Non Alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Other: Placebo; Drug: Tropifexor; Drug: Licogliflozin

Detailed Description

The study consisted of 1) a screening period, 2) a treatment period starting from randomization on Day 0 and running to Week 48, and 3) a follow-up period of 4 weeks after the last dose of study treatment. The study duration from first dose of study medication was 52 weeks.

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Florencio Varela, Buenos Aires, Argentina, C1073ABA
      • Novartis Investigative Site
• Belgium
  • Mechelen, Belgium, 2800
    • Novartis Investigative Site
• Brazil
  • BA
    • Salvador, BA, Brazil, 40110-160
      • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 04037-002
      • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1784
    • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Novartis Investigative Site
• Chile
  • Los Rios
    • Valdivia, Los Rios, Chile, 5110683
      • Novartis Investigative Site
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2540364
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia, 110131
    • Novartis Investigative Site
  • Antioquia
    • Medellin, Antioquia, Colombia, 050001
      • Novartis Investigative Site
    • Rionegro, Antioquia, Colombia, 054047
      • Novartis Investigative Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 10617
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10825
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
• Japan
  • Kagawa
    • Takamatsu city, Kagawa, Japan, 760 8557
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 236-0004
      • Novartis Investigative Site
  • Saga
    • Saga-city, Saga, Japan, 849-8501
      • Novartis Investigative Site
  • Shimane
    • Izumo-city, Shimane, Japan, 693 8501
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul
    • Dongjak Gu, Seoul, Korea, Republic of, 07061
      • Novartis Investigative Site
• Mexico
  • Mexico, Mexico, 22381
    • Novartis Investigative Site
  • Ciudad De Mexico
    • Cuauhtemoc, Ciudad De Mexico, Mexico, 06700
      • Novartis Investigative Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Novartis Investigative Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • FDI Clinical Research
• Russian Federation
  • Novosibirsk, Russian Federation, 630090
    • Novartis Investigative Site
  • Samara, Russian Federation, 443063
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 199226
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 199034
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7531
    • Novartis Investigative Site
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Novartis Investigative Site
  • Tainan, Taiwan, 70403
    • Novartis Investigative Site
• Turkey
  • Topkapi
    • Istanbul, Topkapi, Turkey, 34010
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • Grampian Region
    • Aberdeen, Grampian Region, United Kingdom, AB25 2ZN
      • Novartis Investigative Site
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Gut PC Digestive Health Specialist
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Trials
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • San Diego, California, United States, 92123
      • Medical Associates Research Group
    • Van Nuys, California, United States, 91405
      • San Fernando Valley Health Institute
    • Ventura, California, United States, 93003
      • Island View Gastroenterology Associates
  • Florida
    • Doral, Florida, United States, 33166
      • Integrity Clinical Rsh LLC
    • Lehigh Acres, Florida, United States, 33936
      • Galenus Group
    • Miami, Florida, United States, 33165-7574
      • Genoma Research Group Inc
  • Indiana
    • South Bend, Indiana, United States, 46635
      • Digestive Res Alliance of Michiana
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Adv Res LLC
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals Inc
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Southwest Gastroenterology Associates
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
  • North Carolina
    • Lenoir, North Carolina, United States, 28645
      • Clinical Trials of America LLC
    • Morehead City, North Carolina, United States, 28557
      • Diabetes And Endocrinology Conslt
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health
    • Greenwood, South Carolina, United States, 29646
      • Digestive Disease Research
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
  • Tennessee
    • Hermitage, Tennessee, United States, 37076
      • Summit Medical Care
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Center
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at Texas Liver Institute
    • San Antonio, Texas, United States, 78240
      • Endeavor Clinical Trials
    • Sugar Land, Texas, United States, 77479
      • Pioneer Research Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Presence of NASH with fibrosis confirmed by central reader's evaluation of liver biopsy obtained no more than 6 months before randomization as demonstrated by the following:

1. NASH using NAFLD Activity Score (NAS) ≥ 4 with at least 1 point each in inflammation and ballooning and
2. Fibrosis stage 2 or 3 using NASH CRN fibrosis criteria

Exclusion Criteria:

• Type 1 diabetes mellitus
• Uncontrolled type 2 diabetes defined as glycated hemoglobin (HbA1c) ≥ 9.0% at screening
• HbA1c < 6.5% at screening in Type 2 diabetics currently treated with insulin or sulfonylureas

• Clinical evidence of liver impairment as defined by the presence of any of the following abnormalities:

  • Platelet count < LLN (see Central laboratory manual).
  • Serum albumin < LLN (see Central laboratory manual).
  • International Normalized Ratio (INR) > ULN (see Central laboratory manual).
  • ALT or AST > 5× ULN (confirmed by 2 values during screening).
  • Total bilirubin > ULN (see Central laboratory manual) (confirmed by 2 values during screening), including Gilbert's syndrome.
  • Alkaline phosphatase > 300 IU/L (confirmed by 2 values during screening).
  • History of esophageal varices, ascites or hepatic encephalopathy
  • Splenomegaly
  • MELD score >12

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: combination therapy; Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally	Drug: Tropifexor; 100mcg+30mcg+10mcg capsules of tropifexor taken orally every day until the 140 mcg capsule of tropifexor taken orally every day is produced, then patients will switch to the single 140mcg capsule taken orally every day; Other Names: LJN452; Drug: Licogliflozin; 30mg tablet of licoglifozin taken orally every day; Other Names: LIK066
Experimental: Arm B: tropifexor monotherapy; Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally	Drug: Tropifexor; 100mcg+30mcg+10mcg capsules of tropifexor taken orally every day until the 140 mcg capsule of tropifexor taken orally every day is produced, then patients will switch to the single 140mcg capsule taken orally every day; Other Names: LJN452
Experimental: Arm C: licogliflozin monotherapy; Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally	Drug: Licogliflozin; 30mg tablet of licoglifozin taken orally every day; Other Names: LIK066
Placebo Comparator: Arm D: Placebo; Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily	Other: Placebo; licogliflozin placebo + tropifexor placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological Improvement: Number and Percentage of Participants Who Responded at Week 48 Compared With Baseline	Response was defined as at least a one-stage improvement in fibrosis without worsening of nonalcoholic steatohepatitis (NASH) Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.	Baseline, Week 48
Number and Percentage of Participants With Resolution of NASH and no Worsening of Fibrosis	Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants Who Achieved Resolution of NASH and no Worsening of Fibrosis OR Improvement in Fibrosis by at Least One Stage Without Worsening of NASH	Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.	48 weeks
Number and Percentage of Participants With at Least One Stage Improvement in Fibrosis	Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.	48 weeks
Number and Percentage of Participants With at Least Two Stage Improvement in Fibrosis Without Worsening of NASH	Fibrosis staging and Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.	48 weeks
Number and Percentage of Participants Achieving 5% or More Reduction in Body Weight at Week 48 Compared With Baseline	Whether the participants had 5% or more reduction in body weight.	Baseline, Week 48
Change From Baseline to Week 48 in Percent Liver Fat Content Based on Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI - PDFF)	Change in liver fat content based on MRI-PDFF.	Baseline, Week 48
Change From Baseline in Alanine Transaminase (ALT) Over Time	To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.	Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
Change From Baseline in Aspartate Aminotransferase (AST) Over Time	To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.	Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time	To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.	Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Patient Lay Trial Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Actual): October 27, 2022
• Study Completion (Actual): October 27, 2022

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: NASH; Placebo; LIK066; Non alcoholic steatohepatitis; Tropifexor; LJN452; Licogliflozin
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Licogliflozin
• Other Study ID Numbers: CLJN452D12201C; 2019-002324-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No