Back to resultsA Study of the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD
Primary Purpose
Nonalcoholic Fatty Liver
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PXL770
Placebo Oral Capsule
Sponsored by
About this trial
This is an interventional treatment trial for Nonalcoholic Fatty Liver
Eligibility Criteria
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
Sites / Locations
- Study Site 02
- Study Site 01
- Study Site 11
- Study Site 15
- Study Site 10
- Study Site 03
- Study Site 07
- Study Site 05
- Study Site 08
- Study Site 09
- Study Site 13
- Study Site 06
- Study Site 04
- Study Site 12
- Study Site 14
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Group 1
Group 2
Group 3
Group 4
Arm Description
PXL770 Dose 1
PXL770 Dose 2
PXL770 Dose 3
Placebo oral capsule
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03763877
Brief Title
A Study of the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
March 29, 2019 (Actual)
Primary Completion Date
August 3, 2020 (Actual)
Study Completion Date
August 10, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Poxel SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Fatty Liver
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
121 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
PXL770 Dose 1
Arm Title
Group 2
Arm Type
Experimental
Arm Description
PXL770 Dose 2
Arm Title
Group 3
Arm Type
Experimental
Arm Description
PXL770 Dose 3
Arm Title
Group 4
Arm Type
Placebo Comparator
Arm Description
Placebo oral capsule
Intervention Type
Drug
Intervention Name(s)
PXL770
Intervention Description
Oral capsule
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Capsule
Intervention Description
Oral capsule
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Baseline to Week 12
Title
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)
Description
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.
Time Frame
Baseline to Week 12
Title
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)
Description
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.
Time Frame
Baseline to Week 12
Title
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])
Description
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.
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
Absolute Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment
Description
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
Time Frame
Baseline to Week 12
Title
Change in Alanine Amino Transferase (ALT) From Baseline to Week 12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Aspartate Amino Transferase (AST) From Baseline to Week 12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Fasting Plasma Glucose (FPG) From Baseline to Week12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Glycated Hemoglobin (HbA1c) From Baseline to Week12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Total Cholesterol From Baseline to Week12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in High Density Lipoprotein-Cholesterol (HDL-C) From Baseline to Week12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Week12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Triglycerides From Baseline to Week12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Fibrosis-4 (Fib-4) Score From Baseline to Week 12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
Title
Change in Body Weight From Baseline to Week 12/End of Treatment
Description
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.
Time Frame
Baseline to Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Study Site 02
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Facility Name
Study Site 01
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Study Site 11
City
Ocoee
State/Province
Florida
ZIP/Postal Code
34761
Country
United States
Facility Name
Study Site 15
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Study Site 10
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Study Site 03
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Study Site 07
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
Facility Name
Study Site 05
City
West Monroe
State/Province
Louisiana
ZIP/Postal Code
71291
Country
United States
Facility Name
Study Site 08
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Study Site 09
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Study Site 13
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
Study Site 06
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Study Site 04
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207
Country
United States
Facility Name
Study Site 12
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Study Site 14
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34560015
Citation
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.
Results Reference
derived
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/34560015/
Description
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A Study of the Efficacy and Safety of PXL770 Versus Placebo After 12 Weeks of Treatment in Patients With NAFLD
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