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

NCT03763877 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PXL770-004
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 15

Brief Summary

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

Conditions

Nonalcoholic Fatty Liver

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (12)

• 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

• Percentage of Responders (Relative Reduction of at Least 30% in Liver Fat Mass) at Week 12/End of Treatment

  Baseline to Week 12

• Change in Alanine Amino Transferase (ALT) From Baseline to Week 12/End of Treatment

  Baseline to Week 12

• Change in Aspartate Amino Transferase (AST) From Baseline to Week 12/End of Treatment

  Baseline to Week 12

• Change in Fasting Plasma Glucose (FPG) From Baseline to Week12/End of Treatment

  Baseline to Week 12

Study Arms (4)

Group 1

EXPERIMENTAL

PXL770 Dose 1

Drug: PXL770

Group 2

EXPERIMENTAL

PXL770 Dose 2

Drug: PXL770

Group 3

EXPERIMENTAL

PXL770 Dose 3

Drug: PXL770

Group 4

PLACEBO COMPARATOR

Placebo oral capsule

Drug: Placebo Oral Capsule

Interventions

PXL770 DRUG

Oral capsule

Group 1; Group 2; Group 3

Placebo Oral Capsule DRUG

Oral capsule

Group 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Poxel SA: lead

Study Sites (15)

Study Site 02

Los Angeles, California, 90057, United States

Location

Study Site 01

Gainesville, Florida, 32610, United States

Location

Study Site 11

Ocoee, Florida, 34761, United States

Location

Study Site 15

Orlando, Florida, 32804, United States

Location

Study Site 10

Athens, Georgia, 30607, United States

Location

Study Site 03

Indianapolis, Indiana, 46260, United States

Location

Study Site 07

Marrero, Louisiana, 70072, United States

Location

Study Site 05

West Monroe, Louisiana, 71291, United States

Location

Study Site 08

Berlin, New Jersey, 08009, United States

Location

Study Site 09

Durham, North Carolina, 27710, United States

Location

Study Site 13

Rapid City, South Dakota, 57701, United States

Location

Study Site 06

Arlington, Texas, 76012, United States

Location

Study Site 04

San Antonio, Texas, 78207, United States

Location

Study Site 12

San Antonio, Texas, 78215, United States

Location

Study Site 14

Richmond, Virginia, 23294, United States

Location

Related Publications (1)

• 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.

  PMID: 34560015 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

2-chloro-3-(1-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-6-oxo-5-phenyl-7H-thieno)(2,3-b)pyridin-4-olate potassium

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Director, Medical Operations
• Organization: Poxel

carole.thang@poxelpharma.com

+33 (0)4 37 37 20 10

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2018
• First Posted: December 4, 2018
• Study Start: March 29, 2019
• Primary Completion: August 3, 2020
• Study Completion: August 10, 2020
• Last Updated: October 28, 2021
• Results First Posted: October 28, 2021

Record last verified: 2021-10

Locations

US (15)