Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.)

Criterios de exclusión

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

Intervenciones

drug

LYS006

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

drug

Tropifexor

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

Ubicaciones

Novartis Investigative Site

Buenos Aires, Argentina

Patrocinadores

PrincipalNovartis Pharmaceuticals