Clinical trial NCT03763877: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Fatty Liver
Lead sponsor: Poxel SA
Sponsor class: INDUSTRY
First posted: 2018-12-04
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: 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)
timeFrame: Baseline to Week 12
measure: 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)
timeFrame: Baseline to Week 12
measure: 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)
timeFrame: Baseline to Week 12
measure: 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])
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Absolute Change in the Percentage of Liver Fat Mass (Assessed by MRI-PDFF) From Baseline to Week 12/End of Treatment
timeFrame: Baseline to Week 12
measure: Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Alanine Amino Transferase (ALT) From Baseline to Week 12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Aspartate Amino Transferase (AST) From Baseline to Week 12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Glycated Hemoglobin (HbA1c) From Baseline to Week12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Total Cholesterol From Baseline to Week12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in High Density Lipoprotein-Cholesterol (HDL-C) From Baseline to Week12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Low Density Lipoprotein-Cholesterol (LDL-C) From Baseline to Week12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Triglycerides From Baseline to Week12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Fibrosis-4 (Fib-4) Score From Baseline to Week 12/End of Treatment
timeFrame: Baseline to Week 12
measure: Change in Body Weight From Baseline to Week 12/End of Treatment
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Study Site 02
state: California
city: Gainesville
country: United States
facility: Study Site 01
state: Florida
city: Ocoee
country: United States
facility: Study Site 11
state: Florida
city: Orlando
country: United States
facility: Study Site 15
state: Florida
city: Athens
country: United States
facility: Study Site 10
state: Georgia
city: Indianapolis
country: United States
facility: Study Site 03
state: Indiana
city: Marrero
country: United States
facility: Study Site 07
state: Louisiana
city: West Monroe
country: United States
facility: Study Site 05
state: Louisiana
city: Berlin
country: United States
facility: Study Site 08
state: New Jersey
city: Durham
country: United States
facility: Study Site 09
state: North Carolina
city: Rapid City
country: United States
facility: Study Site 13
state: South Dakota
city: Arlington
country: United States
facility: Study Site 06
state: Texas
city: San Antonio
country: United States
facility: Study Site 04
state: Texas
city: San Antonio
country: United States
facility: Study Site 12
state: Texas
city: Richmond
country: United States
facility: Study Site 14
state: Virginia
Study officials:
References:
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.