A Study of the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD

Nonalcoholic Fatty Liver Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Assess the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03763877
• Other study ID #: PXL770-004
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2019
• Est. completion date: August 10, 2020

Study information

• Verified date: October 2021
• Source: Poxel SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of 3 doses of PXL770 versus placebo after 12 weeks of treatment.

Description:

The study will be performed in patients with Nonalcoholic Fatty Liver Disease. The primary endpoint will be the assessment of the change in the percentage of liver fat mass (assessed by MRI-PDFF).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: August 10, 2020
• Est. primary completion date: August 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients have given written informed consent
• Body mass index (BMI) = 25 to = 50 kg/m²
• For patients with type 2 diabetes mellitus: either naive of glucose lowering drug or under stable oral glucose lowering drug
• Estimated glomerular filtration rate (eGFR) = 60 mL/[min*1.73m²]
• Alanine amino transferase (ALT) > 20 IU/L in females and > 30 IU/L in males
• Hepatic steatosis (MRI-PDFF = 10%)
• Effective contraception for women of child bearing potential

Exclusion Criteria:

• Evidence of another form of liver disease
• Evidence of liver cirrhosis
• Evidence of hepatic impairment
• Positive serologic evidence of current infectious liver disease
• History of excessive alcohol intake
• Acute cardiovascular disease with 24 weeks prior to screening
• Uncontrolled high blood pressure
• Any disease which in the Investigator's opinion which in the Investigator's opinion would exclude the patient from the study
• Use of non-permitted concomitant medication
• Pregnancy or lactation

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver

Intervention

Drug:
• PXL770
Oral capsule
• Placebo Oral Capsule
Oral capsule

Locations

Country	Name	City	State
United States	Study Site 06	Arlington	Texas
United States	Study Site 10	Athens	Georgia
United States	Study Site 08	Berlin	New Jersey
United States	Study Site 09	Durham	North Carolina
United States	Study Site 01	Gainesville	Florida
United States	Study Site 03	Indianapolis	Indiana
United States	Study Site 02	Los Angeles	California
United States	Study Site 07	Marrero	Louisiana
United States	Study Site 11	Ocoee	Florida
United States	Study Site 15	Orlando	Florida
United States	Study Site 13	Rapid City	South Dakota
United States	Study Site 14	Richmond	Virginia
United States	Study Site 04	San Antonio	Texas
United States	Study Site 12	San Antonio	Texas
United States	Study Site 05	West Monroe	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Poxel SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative Change in the Percentage of Liver Fat Mass (Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction [MRI-PDFF]) From Baseline to Week 12/End of Treatment (EOT)	MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 region of interest (ROI) was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint.	Baseline to Week 12
Primary	Relative Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment (Per Protocol Sensitivity Analysis)	MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint.	Baseline to Week 12
Primary	Relative Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment (Unstratified Wilcoxon Sensitivity Analysis)	MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint.	Baseline to Week 12
Primary	Relative Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment (Subgroup Analysis - Type 2 Diabetes Mellitus [T2DM])	MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint.	Baseline to Week 12
Secondary	Absolute Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment	MRI acquisitions were performed at pre-qualified local MRI facilities using qualified and standardized instruments at high field strength (3 T or 1.5T) without oral or intravenous contrast. All acquisitions images were transferred to a central reader vendor for central calculation and measurement of MRI-PDFF using the method of Zhong et al. to estimate water and fat components. A 3 cm2 ROI was placed in each Couinaud segment. Central reading was masked to treatment group, clinical data, study site of origin and timepoint.	Baseline to Week 12
Secondary	Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment	Responders were defined as patients who achieved a clinically meaningful relative reduction of at least 30% in liver fat mass From baseline to Week 12/EOT as assessed by MRI-PDFF	Baseline to Week 12
Secondary	Change in Alanine Amino Transferase (ALT) From Baseline to Week 12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Aspartate Amino Transferase (AST) From Baseline to Week 12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Week12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Glycated Hemoglobin (HbA1c) From Baseline to Week12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Total Cholesterol From Baseline to Week12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in High Density Lipoprotein-Cholesterol (HDL-C) From Baseline to Week12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Week12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Triglycerides From Baseline to Week12/End of Treatment	Blood samples were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Fibrosis-4 (Fib-4) Score From Baseline to Week 12/End of Treatment	Fib-4 score is a non invasive method based on clinical determinations that indicates the level of fibrosis/ scarring of the liver. The set cutoffs for this scoring are: Fib-4 < 1.45: absence of cirrhosis; Fib-4 between 1.45 - 3.25: inconclusive and Fib-4 > 3.25: cirrhosis.; Fib-4 score was calculated as (Age [years] × AST [U/L]) / (platelet [10^9/L] × v[ALT [U/L]]). Blood samples used for AST, ALT and platelet counts were collected, handled and stored according to the instructions described in the laboratory manual and all measurements were performed at a central laboratory.	Baseline to Week 12
Secondary	Change in Body Weight From Baseline to Week 12/End of Treatment	Body weight was measured using a scale with appropriate resolution, placed on a stable, flat surface. Shoes, bulky layers of clothing, and jackets had to be removed so that only light clothing remained.	Baseline to Week 12

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