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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Non-alcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis

Treatments: Drug: LYS006; Drug: Tropifexor

Study type: Interventional

Funder types: Industry

Identifiers

NCT04147195

2018-002692-17 (EudraCT Number)

CADPT02A12001

Details and patient eligibility

About

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.

Full description

This was a Phase II, non-confirmatory, multicenter, open label, platform study in NAFLD participants with a NASH-like biomarker phenotype to examine the effects of single and combination therapies over 12 weeks of treatment. The study consisted of four distinct study periods:

• Screening Period (Day -60 to -28): Lasted up to a maximum of 33 days where participants were assessed for inclusion and exclusion criteria prior the baseline assessments.
• Baseline Period (Day -27 to -1): Lasted up to a maximum of 27 days and comprised baseline assessments and randomization.
• Treatment Period (Day 1 to 85): Participants were randomized in a 1:1 ratio to LYS006 20 mg (twice a day) arm or to LYS006 20 mg (twice a day) and tropifexor 200ug (once a day). Participants were treated daily during 12 weeks.
• Follow-up Period (Day 85 to 113): After completion of the treatment period, participants were observed until the End Of Study (EOS) visit at Day 113.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.)

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

41 participants in 2 patient groups

LYS006

Experimental group

Description:

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

Treatment:

Drug: LYS006

LYS006 + LJN452

Experimental group

Description:

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

Treatment:

Drug: Tropifexor