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

NCT ID: NCT04065841

Last Updated: 2025-01-28

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

234 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-30

Study Completion Date

2022-10-27

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non Alcoholic Steatohepatitis (NASH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm B: tropifexor monotherapy

Tropifexor monotherapy arm: tropifexor 140 mcg capsule (+ placebo matching licogliflozin tablet), once daily orally

Group Type EXPERIMENTAL

Tropifexor

Intervention Type DRUG

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

Arm C: licogliflozin monotherapy

Licogliflozin monotherapy arm: licogliflozin 30 mg tablet (+ placebo matching tropifexor capsule), once daily orally

Group Type EXPERIMENTAL

Licogliflozin

Intervention Type DRUG

30mg tablet of licoglifozin taken orally every day

Arm D: Placebo

Placebo arm: placebo matching tropifexor capsule + placebo matching licogliflozin tablet, once daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

licogliflozin placebo + tropifexor placebo

Arm A: combination therapy

Combination therapy arm: tropifexor 140 mcg capsule + licogliflozin 30 mg tablet, once daily orally

Group Type EXPERIMENTAL

Tropifexor

Intervention Type DRUG

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

Licogliflozin

Intervention Type DRUG

30mg tablet of licoglifozin taken orally every day

Interventions

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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

Intervention Type DRUG

Licogliflozin

30mg tablet of licoglifozin taken orally every day

Intervention Type DRUG

Placebo

licogliflozin placebo + tropifexor placebo

Intervention Type OTHER

Other Intervention Names

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LJN452 LIK066

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Gut PC Digestive Health Specialist

Dothan, Alabama, United States

Site Status

Southern California Research Center

Coronado, California, United States

Site Status

Velocity Clinical Trials

Los Angeles, California, United States

Site Status

California Liver Research Institute

Pasadena, California, United States

Site Status

Medical Associates Research Group

San Diego, California, United States

Site Status

San fernando Valley Health Institute

Van Nuys, California, United States

Site Status

Island View Gastroenterology Associates

Ventura, California, United States

Site Status

Integrity Clinical Rsh LLC

Doral, Florida, United States

Site Status

Galenus Group

Lehigh Acres, Florida, United States

Site Status

Genoma Research Group Inc

Miami, Florida, United States

Site Status

Digestive Res Alliance of Michiana

South Bend, Indiana, United States

Site Status

Southern Therapy and Adv Res LLC

Jackson, Mississippi, United States

Site Status

Clinical Research Professionals Inc

Chesterfield, Missouri, United States

Site Status

Southwest Gastroenterology Associates

Albuquerque, New Mexico, United States

Site Status

Northwell Health

Manhasset, New York, United States

Site Status

Clinical Trials Of America LLC

Lenoir, North Carolina, United States

Site Status

Diabetes And Endocrinology Conslt

Morehead City, North Carolina, United States

Site Status

Options Health Research

Tulsa, Oklahoma, United States

Site Status

Prisma Health

Greenville, South Carolina, United States

Site Status

Digestive Disease Research

Greenwood, South Carolina, United States

Site Status

Palmetto Clinical Research

Summerville, South Carolina, United States

Site Status

Summit Medical Care

Hermitage, Tennessee, United States

Site Status

Texas Clinical Research Institute

Arlington, Texas, United States

Site Status

Dallas Diabetes and Endocrine Center

Dallas, Texas, United States

Site Status

American Research Corporation at Texas Liver Institute

San Antonio, Texas, United States

Site Status

Clinical Trials of Texas

San Antonio, Texas, United States

Site Status

Endeavor Clinical Trials

San Antonio, Texas, United States

Site Status

Pioneer Research Solutions

Sugar Land, Texas, United States

Site Status

Novartis Investigative Site

San Juan Bautista, Buenos Aires, Argentina

Site Status

Novartis Investigative Site

Mechelen, , Belgium

Site Status

Novartis Investigative Site

Salvador, Estado de Bahia, Brazil

Site Status

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status

Novartis Investigative Site

Sofia, , Bulgaria

Site Status

Novartis Investigative Site

Sofia, , Bulgaria

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Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Valdivia, Los Ríos Region, Chile

Site Status

Novartis Investigative Site

Viña del Mar, Región de Valparaíso, Chile

Site Status

Novartis Investigative Site

Medellín, Antioquia, Colombia

Site Status

Novartis Investigative Site

Rionegro, Antioquia, Colombia

Site Status

Novartis Investigative Site

Bogotá, , Colombia

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Novartis Investigative Site

Aarhus N, , Denmark

Site Status

Novartis Investigative Site

Tallinn, , Estonia

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Novartis Investigative Site

Berlin, , Germany

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Novartis Investigative Site

Dresden, , Germany

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Novartis Investigative Site

Essen, , Germany

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Novartis Investigative Site

Mainz, , Germany

Site Status

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, India

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Rozzano, MI, Italy

Site Status

Novartis Investigative Site

Palermo, PA, Italy

Site Status

Novartis Investigative Site

Padua, PD, Italy

Site Status

Novartis Investigative Site

Takamatsu, Kagawa-ken, Japan

Site Status

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Site Status

Novartis Investigative Site

Saga, Saga-ken, Japan

Site Status

Novartis Investigative Site

Izumo, Shimane, Japan

Site Status

Novartis Investigative Site

Guadalajara, Jalisco, Mexico

Site Status

Novartis Investigative Site

Cuauhtémoc, Mexico City, Mexico

Site Status

Novartis Investigative Site

Monterrey, Nuevo León, Mexico

Site Status

Novartis Investigative Site

México, , Mexico

Site Status

FDI Clinical Research

San Juan, , Puerto Rico

Site Status

Novartis Investigative Site

Novosibirsk, , Russia

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Samara, , Russia

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Port Elizabeth, Eastern Cape, South Africa

Site Status

Novartis Investigative Site

Cape Town, , South Africa

Site Status

Novartis Investigative Site

Dongjak Gu, Seoul, South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Kaohsiung City, , Taiwan

Site Status

Novartis Investigative Site

Tainan City, , Taiwan

Site Status

Novartis Investigative Site

Istanbul, Topkapi, Turkey (Türkiye)

Site Status

Novartis Investigative Site

Aberdeen, Grampian Region, United Kingdom

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Countries

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United States Argentina Belgium Brazil Bulgaria Canada Chile Colombia Denmark Estonia Germany India Italy Japan Mexico Puerto Rico Russia Singapore South Africa South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2019-002324-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLJN452D12201C

Identifier Type: -

Identifier Source: org_study_id

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