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

NCT04065841 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLJN452D12201C2019-002324-32
• Study Type: interventional
• Target: 234
• Locations: 23 countries
• Sites: 77

Brief Summary

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.

Conditions

Non Alcoholic Steatohepatitis (NASH)

Keywords

NASH; Non alcoholic steatohepatitis; Tropifexor; LJN452; Licogliflozin; LIK066; Placebo

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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

  48 weeks

• Number and Percentage of Participants With at Least One Stage Improvement in Fibrosis

  48 weeks

• Number and Percentage of Participants With at Least Two Stage Improvement in Fibrosis Without Worsening of NASH

  48 weeks

• Number and Percentage of Participants Achieving 5% or More Reduction in Body Weight at Week 48 Compared With Baseline

  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)

  Baseline, Week 48

Study Arms (4)

Arm A: combination therapy

EXPERIMENTAL

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

Drug: Tropifexor; Drug: Licogliflozin

Arm B: tropifexor monotherapy

EXPERIMENTAL

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

Drug: Tropifexor

Arm C: licogliflozin monotherapy

EXPERIMENTAL

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

Drug: Licogliflozin

Arm D: Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Tropifexor 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

Also known as: LJN452

Arm A: combination therapy; Arm B: tropifexor monotherapy

Licogliflozin DRUG

30mg tablet of licoglifozin taken orally every day

Also known as: LIK066

Arm A: combination therapy; Arm C: licogliflozin monotherapy

Placebo OTHER

licogliflozin placebo + tropifexor placebo

Arm D: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (80)

Gut PC Digestive Health Specialist

Dothan, Alabama, 36305, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

Velocity Clinical Trials

Los Angeles, California, 90057, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

San fernando Valley Health Institute

Van Nuys, California, 91405, United States

Location

Island View Gastroenterology Associates

Ventura, California, 93003, United States

Location

Integrity Clinical Rsh LLC

Doral, Florida, 33166, United States

Location

Galenus Group

Lehigh Acres, Florida, 33936, United States

Location

Genoma Research Group Inc

Miami, Florida, 33165-7574, United States

Location

Digestive Res Alliance of Michiana

South Bend, Indiana, 46635, United States

Location

Southern Therapy and Adv Res LLC

Jackson, Mississippi, 39216, United States

Location

Clinical Research Professionals Inc

Chesterfield, Missouri, 63005, United States

Location

Southwest Gastroenterology Associates

Albuquerque, New Mexico, 87109, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Clinical Trials Of America LLC

Lenoir, North Carolina, 28645, United States

Location

Diabetes And Endocrinology Conslt

Morehead City, North Carolina, 28557, United States

Location

Options Health Research

Tulsa, Oklahoma, 74104, United States

Location

Prisma Health

Greenville, South Carolina, 29605, United States

Location

Digestive Disease Research

Greenwood, South Carolina, 29646, United States

Location

Palmetto Clinical Research

Summerville, South Carolina, 29485, United States

Location

Summit Medical Care

Hermitage, Tennessee, 37076, United States

Location

Texas Clinical Research Institute

Arlington, Texas, 76012, United States

Location

Dallas Diabetes and Endocrine Center

Dallas, Texas, 75230, United States

Location

American Research Corporation at Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Endeavor Clinical Trials

San Antonio, Texas, 78240, United States

Location

Pioneer Research Solutions

Sugar Land, Texas, 77479, United States

Location

Novartis Investigative Site

San Juan Bautista, Buenos Aires, C1073ABA, Argentina

Location

Novartis Investigative Site

Mechelen, 2800, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 40110-160, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04037-002, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Sofia, 1413, Bulgaria

Location

Novartis Investigative Site

Sofia, 1784, Bulgaria

Location

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

Location

Novartis Investigative Site

Valdivia, Los Ríos Region, 5110683, Chile

Location

Novartis Investigative Site

Viña del Mar, Región de Valparaíso, 2540364, Chile

Location

Novartis Investigative Site

Medellín, Antioquia, 050001, Colombia

Location

Novartis Investigative Site

Rionegro, Antioquia, 054047, Colombia

Location

Novartis Investigative Site

Bogotá, 110131, Colombia

Location

Novartis Investigative Site

Aarhus N, 8200, Denmark

Location

Novartis Investigative Site

Tallinn, 10617, Estonia

Location

Novartis Investigative Site

Berlin, 10825, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110070, India

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Takamatsu, Kagawa-ken, 760 8557, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 236-0004, Japan

Location

Novartis Investigative Site

Saga, Saga-ken, 849-8501, Japan

Location

Novartis Investigative Site

Izumo, Shimane, 693 8501, Japan

Location

Novartis Investigative Site

Guadalajara, Jalisco, 44130, Mexico

Location

Novartis Investigative Site

Cuauhtémoc, Mexico City, 06700, Mexico

Location

Novartis Investigative Site

Monterrey, Nuevo León, 64460, Mexico

Location

Novartis Investigative Site

México, 22381, Mexico

Location

FDI Clinical Research

San Juan, 00927, Puerto Rico

Location

Novartis Investigative Site

Novosibirsk, 630090, Russia

Location

Novartis Investigative Site

Saint Petersburg, 199034, Russia

Location

Novartis Investigative Site

Saint Petersburg, 199226, Russia

Location

Novartis Investigative Site

Samara, 443063, Russia

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Novartis Investigative Site

Cape Town, 7531, South Africa

Location

Novartis Investigative Site

Dongjak Gu, Seoul, 07061, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Kaohsiung City, 80756, Taiwan

Location

Novartis Investigative Site

Tainan, 70403, Taiwan

Location

Novartis Investigative Site

Istanbul, Topkapi, 34010, Turkey (Türkiye)

Location

Novartis Investigative Site

Aberdeen, Grampian Region, AB25 2ZN, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

tropifexor; licogliflozin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

(862) 778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 22, 2019
• Study Start: December 30, 2019
• Primary Completion: October 27, 2022
• Study Completion: October 27, 2022
• Last Updated: January 28, 2025
• Results First Posted: December 26, 2023

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); AR (1); BU (2); CO (3); US (28); DK (1); SG (2); IT (4); DE (4); ES (1); BE (1); CL (2); ZA (2); BR (4); IN (1); ME (4); PR (1); RU (4); CA (1); KR (2); JP (4); TU (1); TW (2)