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

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

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

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Fatty Liver
• Intervention / Treatment: Drug: PXL770; Drug: Placebo Oral Capsule

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • Study site 02
  • Florida
    • Gainesville, Florida, United States, 32610
      • Study site 01
    • Ocoee, Florida, United States, 34761
      • Study site 11
    • Orlando, Florida, United States, 32804
      • Study site 15
  • Georgia
    • Athens, Georgia, United States, 30607
      • Study site 10
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Study site 03
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Study Site 07
    • West Monroe, Louisiana, United States, 71291
      • Study site 05
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Study Site 08
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Study site 09
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Study site 13
  • Texas
    • Arlington, Texas, United States, 76012
      • Study site 06
    • San Antonio, Texas, United States, 78207
      • Study site 04
    • San Antonio, Texas, United States, 78215
      • Study site 12
  • Virginia
    • Richmond, Virginia, United States, 23294
      • Study site 14

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; PXL770 Dose 1	Drug: PXL770; Oral capsule
EXPERIMENTAL: Group 2; PXL770 Dose 2	Drug: PXL770; Oral capsule
EXPERIMENTAL: Group 3; PXL770 Dose 3	Drug: PXL770; Oral capsule
PLACEBO_COMPARATOR: Group 4; Placebo oral capsule	Drug: Placebo Oral Capsule; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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] × √[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
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

Collaborators and Investigators

• Sponsor: Poxel SA

Publications and helpful links

General Publications

• Cusi K, Alkhouri N, Harrison SA, Fouqueray P, Moller DE, Hallakou-Bozec S, Bolze S, Grouin JM, Jeannin Megnien S, Dubourg J, Ratziu V. Efficacy and safety of PXL770, a direct AMP kinase activator, for the treatment of non-alcoholic fatty liver disease (STAMP-NAFLD): a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Gastroenterol Hepatol. 2021 Nov;6(11):889-902. doi: 10.1016/S2468-1253(21)00300-9. Epub 2021 Sep 22.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2019
• Primary Completion (ACTUAL): August 3, 2020
• Study Completion (ACTUAL): August 10, 2020

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (ACTUAL): December 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: PXL770-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No