A Study of the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD
- Conditions
- Nonalcoholic Fatty Liver
- Interventions
- Drug: PXL770Drug: Placebo Oral Capsule
- Registration Number
- NCT03763877
- Lead Sponsor
- Poxel SA
- Brief Summary
This study will assess the efficacy and safety of 3 doses of PXL770 versus placebo after 12 weeks of treatment.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 PXL770 PXL770 Dose 1 Group 2 PXL770 PXL770 Dose 2 Group 3 PXL770 PXL770 Dose 3 Group 4 Placebo Oral Capsule Placebo oral capsule
- Primary Outcome Measures
Name Time Method 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) Baseline to Week 12 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.
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) Baseline to Week 12 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.
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) Baseline to Week 12 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.
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]) Baseline to Week 12 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.
- Secondary Outcome Measures
Name Time Method Change in High Density Lipoprotein-Cholesterol (HDL-C) From Baseline to Week12/End of Treatment Baseline to Week 12 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.
Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Week12/End of Treatment Baseline to Week 12 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.
Change in Triglycerides From Baseline to Week12/End of Treatment Baseline to Week 12 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.
Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment Baseline to Week 12 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
Change in Alanine Amino Transferase (ALT) From Baseline to Week 12/End of Treatment Baseline to Week 12 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.
Change in Body Weight From Baseline to Week 12/End of Treatment Baseline to Week 12 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.
Change in Aspartate Amino Transferase (AST) From Baseline to Week 12/End of Treatment Baseline to Week 12 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.
Absolute Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment Baseline to Week 12 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.
Change in Fibrosis-4 (Fib-4) Score From Baseline to Week 12/End of Treatment Baseline to Week 12 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.Change in Fasting Plasma Glucose (FPG) From Baseline to Week12/End of Treatment Baseline to Week 12 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.
Change in Glycated Hemoglobin (HbA1c) From Baseline to Week12/End of Treatment Baseline to Week 12 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.
Change in Total Cholesterol From Baseline to Week12/End of Treatment Baseline to Week 12 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.
Trial Locations
- Locations (15)
Study Site 15
🇺🇸Orlando, Florida, United States
Study Site 02
🇺🇸Los Angeles, California, United States
Study Site 01
🇺🇸Gainesville, Florida, United States
Study Site 11
🇺🇸Ocoee, Florida, United States
Study Site 03
🇺🇸Indianapolis, Indiana, United States
Study Site 09
🇺🇸Durham, North Carolina, United States
Study Site 06
🇺🇸Arlington, Texas, United States
Study Site 12
🇺🇸San Antonio, Texas, United States
Study Site 04
🇺🇸San Antonio, Texas, United States
Study Site 14
🇺🇸Richmond, Virginia, United States
Study Site 05
🇺🇸West Monroe, Louisiana, United States
Study Site 13
🇺🇸Rapid City, South Dakota, United States
Study Site 07
🇺🇸Marrero, Louisiana, United States
Study Site 08
🇺🇸Berlin, New Jersey, United States
Study Site 10
🇺🇸Athens, Georgia, United States