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

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

Detailed Description
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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).

Official Title
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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

Conditions
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Nonalcoholic Fatty Liver

Intervention / Treatment
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* Drug: PXL770
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>PXL770 Dose 1 | Drug: PXL770<br>* Oral capsule<br>|
| Experimental: Group 2<br>PXL770 Dose 2 | Drug: PXL770<br>* Oral capsule<br>|
| Experimental: Group 3<br>PXL770 Dose 3 | Drug: PXL770<br>* Oral capsule<br>|
| Placebo Comparator: Group 4<br>Placebo oral capsule | Drug: Placebo Oral Capsule<br>* Oral capsule<br>|

What is the study measuring?
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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 |