Study of ADI-PEG 20 Versus Placebo in Subjects With NASH

NCT05842512 | Recruiting Phase 2 DMC

• 1 other identifier: POLARIS2023-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief Summary

Evaluate efficacy and safety of ADI-PEG 20 in patients with NASH

Conditions

Nonalcoholic Steatohepatitis (NASH)

Keywords

Nonalcoholic Steatohepatitis (NASH); Arginine; Arginine Deiminase; ADI-PEG 20; Pegargiminase

Outcome Measures

Primary Outcomes (1)

• Determine Efficacy of ADI-PEG 20 vs Placebo in the treatment of fatty liver as assessed by change in hepatic fat fraction

  Evaluate absolute change from baseline in hepatic fat fraction assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 24

  24 Weeks

Secondary Outcomes (3)

• Assess the Efficacy of ADI-PEG 20 vs Placebo reflected in the percent change from baseline in hepatic fat fraction at week 24

  24 Weeks

• Assess the safety of ADI-PEG 20 in subjects with NASH

  24 Weeks

• Assess the safety and tolerability of ADI-PEG 20 in subjects with NASH

  24 Weeks

Study Arms (2)

Drug: ADI-PEG 20

EXPERIMENTAL

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)

Drug: ADI-PEG20

Drug: Placebo

PLACEBO COMPARATOR

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)

Other: Placebo

Interventions

ADI-PEG20 DRUG

Treatment for NASH

Also known as: Pegargiminase

Drug: ADI-PEG 20

Placebo OTHER

Treatment for NASH

Drug: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and non-lactating, pregnancy test negative females between 18 - 80 years of age with biopsy proven F1 - F4 (compensated cirrhosis, Child-Pugh A, score ≤6) NASH. Limit F1 fibrosis to ≤ 20% of total subject population.
• Willingness to use appropriate contraceptive measures throughout study treatment and for 90 days thereafter (see Appendix A).
• Body mass index (BMI) \> 23 kg/m2
• Must have confirmation of ≥ 5 % liver fat content on MRI-PDFF at screening.
• Biopsy-proven NASH confirmed by a central pathologist. Must have had a liver biopsy either during the screening period or a historical biopsy conducted within the last 6 months prior to pre-screening with fibrosis stage 1 to 4 (F score, F1-F4) and a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at least a score of 1 in each of the following NAS components:
• Steatosis (scored 0 to 3),
• Ballooning degeneration (scored 0 to 2), and
• Lobular inflammation (scored 0 to 3).
• Must have no evidence of worsening of ALT and AST (within 50%) measurements within 2 months prior to screening (-8 weeks) visits.
• Screening laboratory parameters, as determined by the central laboratory:
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft- Gault equation;
• HbA1c ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to be resulted);
• Hemoglobin ≥ 11 g/dL;
• INR ≤ 1.3, unless due to therapeutic anticoagulation;
• Direct bilirubin ≤ 0.5 mg/dL;

You may not qualify if:

• Weight gain or loss \> 5% in the 3 months prior to randomization or \> 10% in the 6 months prior to screening.
• Type 1 and insulin-dependent Type 2 diabetes.
• Poorly controlled hypertension (blood pressure \[BP\] \> 160/100 mmHg).
• Prior history of decompensated liver disease including ascites, hepatic encephalopathy (HE), or variceal bleeding.
• Chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen \[HBsAg\] positive.
• Chronic hepatitis C virus (HCV) infection (HCV antibody \[Ab\] and HCV ribonucleic acid \[RNA\] positive). Subjects cured of HCV infection less than 1 year prior (based on date of RNA polymerase chain reaction \[PCR\] negative confirmation following conclusion of treatment) to the screening visit are not eligible.
• Prior or planned (during the study period) bariatric surgery (e.g., gastroplasty, roux-en-Y gastric bypass), surgery reversal or removal of intragastric balloon \> 2 years prior to enrollment would be eligible.
• Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis \[PBC\], primary sclerosing cholangitis \[PSC\], autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment.
• History of liver transplantation.
• Subjects with primary cancer, including co-existent second malignancy, with the exception of primary solid tumor with no known active disease present in the opinion of the Investigator which will not affect subject outcome in the setting of current diagnosis.
• Alcohol intake above an average limit of 2 drinks per day for women and 3 drinks per day for men. An alcoholic drink is defined as 12 ounces of regular beer, which is usually about 5% alcohol, 5 ounces of wine, which is typically about 12% alcohol, and 1.5 ounces of distilled spirits, which is about 40% alcohol.
• Human immunodeficiency virus (HIV) infection.
• Unstable cardiovascular disease in the 6 months prior to screening.
• Life expectancy less than 2 years.
• Use of any investigational medication within 30 days or within 5 half-lives of the investigational medication, whichever is longer, prior to screening and throughout the study is prohibited.

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (10)

Ditmanson Medical Foundation Chiayi Christian Hospital；Chiayi Christian Hospital (CYCH)

Chiayi City, Taiwan, 600566, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital(KMUH)

Kaohsiung, Taiwan, 807, Taiwan

RECRUITING

E-Da Hospital (EDH)

Kaohsiung, Taiwan, 824, Taiwan

RECRUITING

Chang Gung Medical Foundation-Kaohsiung (CGMF-KS)

Kaohsiung, Taiwan, 833, Taiwan

RECRUITING

Chang Gung Medical Foundation-Keelung (CGMF-KL)

Keelung, Taiwan, 204, Taiwan

RECRUITING

National Cheng Kung University Hospital (NCKUH)

Tainan, Taiwan, 704, Taiwan

RECRUITING

National Taiwan University Hospital (NTUH)

Taipei, Taiwan, 100229, Taiwan

RECRUITING

Taipei Veterans General Hospital (TPVGH)

Taipei, Taiwan, 112201, Taiwan

RECRUITING

Fu Jen Catholic University Hospital (FJCUH)

Taipei, Taiwan, 243, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou (CGMF-LK)

Taoyuan District, Taiwan, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

ADI PEG20

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• John S Bomalaski

  Polaris Group

  STUDY DIRECTOR

Central Study Contacts

Silvia Lee

CONTACT

02-2656-2727; silvialee@polarispharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a randomized, double-blind trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To evaluate efficacy and safety of ADI-PEG 20 or Placebo in patients with NASH

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: May 6, 2023
• Study Start: September 13, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

TW (10)