Study of Various Treatments in Non-alcoholic Fatty Liver Disease (NAFLD) Patients Who Have Aspects of Non-alcoholic Steatohepatitis (NASH)

NCT04147195 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CADPT02A120012018-002692-17
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 10

Brief Summary

This clinical study was designed to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in adult patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype.

Conditions

Non-alcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis

Keywords

Non-alcoholic fatty liver disease; NAFLD; Non-alcoholic steatohepatitis; NASH; Platform design; LYS006; LJN452; Tropifexor

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Number of participants with AEs and SAEs including significant changes from baseline in vital signs, electrocardiograms and laboratory parameters qualifying and reported as AEs. The number of participants in each category is reported in the table.

  From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 113 Days

Secondary Outcomes (12)

• Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score

  Baseline and Days 57, 85 and EOS (Day 113)

• Change From Baseline in Cholesterol: Fasting Lipid Profile Endpoint

  Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)

• Change From Baseline in Percent Liver Fat at Day 85

  Baseline and Day 85

• Change From Baseline in Total Body Weight

  Baseline and Days 15, 29, 43, 57, 85 and EOS (Day 113)

• Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Day 85

  Baseline and Day 85

Study Arms (2)

LYS006

EXPERIMENTAL

LYS006 20 mg was administered orally twice per day (b.i.d) for 12 weeks

Drug: LYS006

LYS006 + LJN452

EXPERIMENTAL

LYS006 20 mg was administered orally twice per day (b.i.d) in addition to LJN452 200ug administered orally once daily for 12 weeks

Drug: Tropifexor

Interventions

LYS006 DRUG

5 mg LYS006 capsules orally administered 20 mg b.i.d for 12 weeks

LYS006

Tropifexor DRUG

100 ug LJN452 capsules orally administered 200ug once daily for 12 weeks

Also known as: LJN452

LYS006 + LJN452

Eligibility Criteria

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

You may qualify if:

• Phenotypic diagnosis of NASH based on the presence of all of the following:
• ALT ≥ 43 IU/L (males) or ≥ 28 IU/L (females)
• BMI ≥ 27 kg/m2 (race other than Asian) or ≥ 23 kg/m2 (Asian race)
• History of type 2 diabetes mellitus with HbA1c ≤ 9%
• ELF test score ≥ 8.5 and ≤ 10.5
• Liver fat ≥ 8%
• Patients must weigh between 40 kg (88 lbs.) and 150 kg (330 lbs.)

You may not qualify if:

• Use of other investigational drugs within 5 half-lives of randomization or within 3 months, whichever is longer
• Use of obeticholic acid (OCA) or pharmacologically-active weight loss drugs within 1 month of randomization
• Use of strong CYP3A4/5 inhibitors or strong CYP3A4 inducers within 5 half-lives or 7 days of randomization, whichever is longer
• History or presence of other concomitant liver diseases
• History or current diagnosis of ECG abnormalities
• Patients with contraindications to MRI imaging
• Current or history of significant alcohol consumption
• Clinical evidence of hepatic decompensation or severe liver impairment
• Women of child bearing potential (unless on highly effective methods of contraception)
• Presence of liver cirrhosis
• Use of OAT3 inhibitors within 5 half-lives or 7 days of randomization, whichever is longer

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Coronado, California, 92118, United States

Location

Novartis Investigative Site

Los Angeles, California, 90057, United States

Location

Novartis Investigative Site

Miami Lakes, Florida, 33014, United States

Location

Novartis Investigative Site

Marietta, Georgia, 30060, United States

Location

Novartis Investigative Site

Honolulu, Hawaii, 96814, United States

Location

Novartis Investigative Site

South Bend, Indiana, 46635, United States

Location

Novartis Investigative Site

Morehead City, North Carolina, 28557, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78215, United States

Location

Novartis Investigative Site

Buenos Aires, C1012AAR, Argentina

Location

Novartis Investigative Site

Essen, Nordrhine Westphalia, 45136, Germany

Location

Related Publications (1)

• Frias J, Schmouder R, Lawitz E, Zhang Y, Zhou H, Badman MK, Ukomadu C, Weiss HM, Zack J, Yadav B, Martic M, Drakeford C, Koo P, Naoumov NV, Greenbaum LE. Clinical trial: A Phase 2 Randomised Platform Study to Assess Monotherapy and Combination Treatment Regimens in Metabolic Dysfunction-Associated Steatohepatitis. Aliment Pharmacol Ther. 2025 Nov 26. doi: 10.1111/apt.70475. Online ahead of print.

  PMID: 41305844 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

tropifexor

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: November 1, 2019
• Study Start: June 4, 2020
• Primary Completion: January 6, 2022
• Study Completion: January 6, 2022
• Last Updated: August 21, 2023
• Results First Posted: January 26, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); US (8); DE (1)