Clinical trial NCT03205150: Effect of LIK066 on Reduction of Fatty Content in Livers of Obese Patients
Official title: A 12-week Randomized, Patient and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate the Efficacy of LIK066 in Obese Patients With Non-alcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obese Patients With Non-alcoholic Steatohepatitis (NASH)
Keywords: non-alcoholic steatohepatitis
NASH
Obese
Type 2 diabetes mellitus
non-alcoholic fatty liver disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-07-02
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess the effects of LIK066 on a variety of metabolic and inflammation biomarkers in patients with non-alcoholic steatohepatitis (NASH)

Detailed description: This was a a non-confirmatory, multicenter, patient and investigator blinded, randomized, placebo-controlled, parallel group study in patients with non-alcoholic steatohepatitis (NASH).

The study consisted of a 28 day screening period (Day -44 to Day -16), a baseline period of 14 days (Day -15 to Day -1), a treatment period of 12 weeks (Day 1 to Day 84), and a study completion evaluation approximately 28 days after the last drug administration. The patients were advised to maintain their recommended diet during the study.

Patients who met the inclusion/exclusion criteria at screening went to the study site for baseline assessments. All baseline safety evaluation results were available prior to the first dosing.

The study started by enrolling patients into the 150 mg and placebo arms with a randomization ratio of 2:1. After the enrollment of the first 33 patients, the 30 mg arm was added to the study and the randomization ratio changed to a 2:4:1 ratio (150 mg: 30 mg: placebo) to maintain the 2:2:1 ratio across the three groups (150 mg: 30 mg: placebo) at study completion.

Eligibility criteria: Inclusion Criteria:

EITHER

-Histologic confirmed NASH based on liver biopsy obtained 2 years or less before randomization with a fibrosis level of F1, F2 or F3 in the absence of a histological diagnosis of alternative chronic liver disease AND ALT greater than or equal to 50 IU/L (males) or greater than or equal to 35 IU/L (females) at screening.

OR

Phenotypic diagnosis of NASH based on presence of ALL three of the following at screening:

* ALT greater than or equal to 50IU/L (males) or greater than or equal to 35 IU/L (females) AND
* BMI greater than or equal to 27 kg/m\^2 (in patients with a self-identified race other than Asian) or greater than or equal to 23 kg/m\^2 (in patients with a self identified Asian race) AND
* Diagnosis of Type 2 diabetes mellitus by HbA1c: greater than or equal to 6.5 % and less than or equal to 10%
* Patients must weigh no more than 150 kg (330 lbs) to participate in the study.
* Male and female patients 18 years or older at the time of screening visit.

Exclusion Criteria:

* History or presence of other concomitant liver diseases
* History or current diagnosis of ECG abnormalities
* Use of GLP-1 agonists, SGLT2 inhibitors, TZDs, FXR agonists and any pharmacologically active weight loss drugs within 6 weeks of screening and until end of study
* 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 basic contraception methods)
* Presence of liver cirrhosis

Primary outcomes:
measure: Change From Baseline in Alanine Aminotransferase (ALT) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Percent Liver Fat at Week 12
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Total Body Weight at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12.
timeFrame: Baseline, Week 12
measure: Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration
timeFrame: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)
measure: Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration
timeFrame: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)
measure: Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration
timeFrame: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)
measure: Change From Baseline in Aspartate Aminotransferase (AST) at Week 12
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Live Oak
country: United States
facility: Novartis Investigative Site
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: St-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Chia-Yi
country: Taiwan
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
Study officials:
References:
citation: Harrison SA, Manghi FP, Smith WB, Alpenidze D, Aizenberg D, Klarenbeek N, Chen CY, Zuckerman E, Ravussin E, Charatcharoenwitthaya P, Cheng PN, Katchman H, Klein S, Ben-Ari Z, Mendonza AE, Zhang Y, Martic M, Ma S, Kao S, Tanner S, Pachori A, Badman MK, He Y, Ukomadu C, Sicard E. Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study. Nat Med. 2022 Jul;28(7):1432-1438. doi: 10.1038/s41591-022-01861-9. Epub 2022 Jun 20.