Study of PXL065 in Patients With Nonalcoholic Steatohepatitis (NASH)

NCT04321343 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PXL065-003
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 29

Brief Summary

This study will assess the effect of 3 doses of PXL065 versus placebo on liver fat content in NASH patients after 36 weeks of treatment

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (2)

• Relative Change From Baseline to Week 36 in the Percentage of Liver Fat Content (LFC) (Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction [MRI-PDFF])

  MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. Relative change from baseline to Week 36 was calculated as follows: (LFC at Week 36 - LFC at baseline) / LFC at baseline x 100. The primary analysis was performed for the Intent-to-treat Set (ITTS) using an analysis of covariance (ANCOVA) model adjusting for treatment, for stratification factors, and for the baseline LFC as a continuous covariate. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.

  Baseline and Week 36

• Relative Change From Baseline to Week 36 in the Percentage of LFC (Assessed by MRI-PDFF) (Wilcoxon Test Sensitivity Analysis)

  MRI-PDFF was performed using a standardized imaging protocol, and a central reader analyzed the results. The central reader for this study trained the local imaging centers and provided the imaging manual. The sensitivity analysis was performed for the Intent-to-treat Set (ITTS) using a non parametric pairwise Wilcoxon test stratified according to T2DM status and NASH CRN fibrosis scoring system. LFC missing values at Week 36 were imputed using a multivariate imputation approach by fully conditional specification regression method assuming Missing At Random Mechanism.

  Baseline and Week 36

Secondary Outcomes (25)

• Absolute Change From Baseline to Week 36 in the Percentage of LFC (Assessed by MRI-PDFF)

  Baseline and Week 36

• Percentage of Responders (Relative Reduction of at Least 30% in LFC) at Week 36

  Baseline and Week 36

• Change From Baseline to Week 36 in Alanine Amino Transferase (ALT)

  Baseline to Week 36

• Percentage of Responders (Normalization of ALT)

  Baseline to Week 36

• Change From Baseline to Week 36 in Aspartate Amino Transferase (AST)

  Baseline to Week 36

Study Arms (4)

Group 1

EXPERIMENTAL

PXL065 Dose 1

Drug: PXL065

Group 2

EXPERIMENTAL

PXL065 Dose 2

Drug: PXL065

Group 3

EXPERIMENTAL

PXL065 Dose 3

Drug: PXL065

Group 4

PLACEBO COMPARATOR

Placebo oral tablet

Drug: Placebo oral tablet

Interventions

PXL065 DRUG

PXL065 oral tablet

Group 1; Group 2; Group 3

Placebo oral tablet DRUG

Placebo oral tablet

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) ≤ 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) ≥ 45 mL/min/1.73m²
• Liver fat content ≥ 8% on MRI-PDFF
• Qualifying liver biopsy (NAS) ≥ 4 and fibrosis score F1, F2 or F3
• 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 within 6 months prior to Randomization
• 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 (29)

Study site 11

Chandler, Arizona, 85224, United States

Location

Study site 12

Glendale, Arizona, 85306, United States

Location

Study site 13

Tucson, Arizona, 85712, United States

Location

Study site 21

Tucson, Arizona, 85712, United States

Location

Study site 17

Chula Vista, California, 91910, United States

Location

Study site 16

Fresno, California, 93720, United States

Location

Study site 04

Huntington Park, California, 90255, United States

Location

Study site 05

Los Angeles, California, 90057, United States

Location

Study site 22

Orange, California, 92866, United States

Location

Study site 06

Panorama City, California, 90402, United States

Location

Study site 07

Santa Ana, California, 92704, United States

Location

Study site 15

Boca Raton, Florida, 33434, United States

Location

Study site 31

Fort Myers, Florida, 33912, United States

Location

Study site 08

Port Orange, Florida, 32127, United States

Location

Study site 01

Sarasota, Florida, 34240, United States

Location

Study site 28

West Des Moines, Iowa, 50265, United States

Location

Study site 18

Kansas City, Kansas, 61431, United States

Location

Study site 24

Flowood, Mississippi, 39232, United States

Location

Study site 10

Jackson, Mississippi, 39216, United States

Location

Study site 27

East Syracuse, New York, 13057, United States

Location

Study site 14

Fayetteville, North Carolina, 28304, United States

Location

Study site 29

Summerville, South Carolina, 29485, United States

Location

Study site 25

Chattanooga, Tennessee, 37411, United States

Location

Study site 30

Clarksville, Tennessee, 37040, United States

Location

Study Site 02

Germantown, Tennessee, 38138, United States

Location

Study site 19

Austin, Texas, 78746, United States

Location

Study site 09

Edinburg, Texas, 78539, United States

Location

Study site 23

Edinburg, Texas, 78539, United States

Location

Pinnacle Clinical Research (Study site 20)

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Limitations and Caveats

Limitations of this trial included a relatively small sample size and treatment duration. However, given a close relationship to the parent molecule, pioglitazone, the potential for unforeseen safety issues is low and the present results can be viewed as confirmatory with respect to efficacy.

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: March 23, 2020
• First Posted: March 25, 2020
• Study Start: September 1, 2020
• Primary Completion: June 8, 2022
• Study Completion: June 20, 2022
• Last Updated: August 29, 2023
• Results First Posted: August 29, 2023

Record last verified: 2023-08

Locations

US (29)