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)

December 7, 2023 updated by: Novartis Pharmaceuticals

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Buenos Aires
      • Florencio Varela, Buenos Aires, Argentina, C1073ABA
        • Novartis Investigative Site
      • Mechelen, Belgium, 2800
        • Novartis Investigative Site
    • BA
      • Salvador, BA, Brazil, 40110-160
        • Novartis Investigative Site
    • RS
      • Porto Alegre, RS, Brazil, 90035-003
        • Novartis Investigative Site
    • SP
      • Sao Paulo, SP, Brazil, 04037-002
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 05403-000
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1413
        • Novartis Investigative Site
      • Sofia, Bulgaria, 1784
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Novartis Investigative Site
    • Los Rios
      • Valdivia, Los Rios, Chile, 5110683
        • Novartis Investigative Site
    • Valparaiso
      • Vina del Mar, Valparaiso, Chile, 2540364
        • Novartis Investigative Site
      • Bogota, Colombia, 110131
        • Novartis Investigative Site
    • Antioquia
      • Medellin, Antioquia, Colombia, 050001
        • Novartis Investigative Site
      • Rionegro, Antioquia, Colombia, 054047
        • Novartis Investigative Site
      • Aarhus, Denmark, 8000 C
        • Novartis Investigative Site
      • Tallinn, Estonia, 10617
        • Novartis Investigative Site
      • Berlin, Germany, 10825
        • Novartis Investigative Site
      • Dresden, Germany, 01307
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
    • Delhi
      • New Delhi, Delhi, India, 110070
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20112
        • 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
    • 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
      • Seoul, Korea, Republic of, 03080
        • Novartis Investigative Site
    • Seoul
      • Dongjak Gu, Seoul, Korea, Republic of, 07061
        • Novartis Investigative Site
      • 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
      • San Juan, Puerto Rico, 00927
        • Novartis Investigative Site
      • 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, 119074
        • Novartis Investigative Site
      • Singapore, Singapore, 169608
        • Novartis Investigative Site
      • Cape Town, South Africa, 7531
        • Novartis Investigative Site
    • Eastern Cape
      • Port Elizabeth, Eastern Cape, South Africa, 6001
        • Novartis Investigative Site
      • Madrid, Spain, 28046
        • Novartis Investigative Site
      • Madrid, Spain, 28009
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Kaohsiung, Taiwan, 80756
        • Novartis Investigative Site
      • Tainan, Taiwan, 70403
        • Novartis Investigative Site
    • Topkapı
      • Istanbul, Topkapı, Turkey, 34010
        • Novartis Investigative Site
      • Aberdeen, United Kingdom, AB25 2ZN
        • Novartis Investigative Site
      • London, United Kingdom, SE5 9RS
        • Novartis Investigative Site
    • Alabama
      • Dothan, Alabama, United States, 36305
        • Novartis Investigative Site
    • California
      • Coronado, California, United States, 92118
        • Novartis Investigative Site
      • Los Angeles, California, United States, 90057
        • Novartis Investigative Site
      • Pasadena, California, United States, 91105
        • Novartis Investigative Site
      • San Diego, California, United States, 92123
        • Novartis Investigative Site
      • Van Nuys, California, United States, 91405
        • Novartis Investigative Site
      • Ventura, California, United States, 93003
        • Novartis Investigative Site
    • Florida
      • Doral, Florida, United States, 33166
        • Novartis Investigative Site
      • Lehigh Acres, Florida, United States, 33936
        • Novartis Investigative Site
      • Miami, Florida, United States, 33165-7574
        • Novartis Investigative Site
    • Indiana
      • South Bend, Indiana, United States, 46635
        • Novartis Investigative Site
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Novartis Investigative Site
    • Missouri
      • Chesterfield, Missouri, United States, 63005
        • Novartis Investigative Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Novartis Investigative Site
    • New York
      • Manhasset, New York, United States, 11030
        • Novartis Investigative Site
    • North Carolina
      • Lenoir, North Carolina, United States, 28645
        • Novartis Investigative Site
      • Morehead City, North Carolina, United States, 28557
        • Novartis Investigative Site
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
        • Novartis Investigative Site
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Novartis Investigative Site
      • Greenwood, South Carolina, United States, 29646
        • Novartis Investigative Site
      • Summerville, South Carolina, United States, 29485
        • Novartis Investigative Site
    • Tennessee
      • Hermitage, Tennessee, United States, 37076
        • Novartis Investigative Site
    • Texas
      • Arlington, Texas, United States, 76012
        • Novartis Investigative Site
      • Dallas, Texas, United States, 75230
        • Novartis Investigative Site
      • San Antonio, Texas, United States, 78229
        • Novartis Investigative Site
      • San Antonio, Texas, United States, 78240
        • Novartis Investigative Site
      • San Antonio, Texas, United States, 78215
        • Novartis Investigative Site
      • Sugar Land, Texas, United States, 77479
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
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
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
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
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
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
Time Frame: Baseline, Week 48

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
Time Frame: 48 weeks
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
Time Frame: 48 weeks
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
Time Frame: 48 weeks
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
Time Frame: 48 weeks
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
Time Frame: Baseline, Week 48
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)
Time Frame: Baseline, Week 48
Change in liver fat content based on MRI-PDFF.
Baseline, Week 48
Change From Baseline in Alanine Transaminase (ALT) Over Time
Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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
Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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
Time Frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

December 26, 2023

Last Update Submitted That Met QC Criteria

December 7, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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