Nonalcoholic Steatohepatitis (NASH)Phase 2NCT05842512
Study of ADI-PEG 20 Versus Placebo in Subjects With NASH
A Phase 2 study testing ADI-PEG20 in people with Nonalcoholic Steatohepatitis (NASH), run by Polaris Group at 10 sites in Taiwan.
Trial summary
Evaluate efficacy and safety of ADI-PEG 20 in patients with NASH Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis (NASH)
- What is being tested?
- ADI-PEG20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 10 sitesTaiwan
- Study dates
- 13 Sep 2023to 31 Jan 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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),
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- 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;
- Total bilirubin ≤ 1.3 x upper limit of normal (ULN), unless due to an alternate etiology such as Gilbert's syndrome or hemolytic anemia;
- Creatinine kinase < 3 x ULN;
- Platelet count ≥ 150,000/μL;
- Serum triglyceride level ≤ 500 mg/dL;
- ALT < 6 x ULN;
- AST < 6 x ULN;
- ALP < 2 x ULN.
- FibroScan® measurement > 7.0 kPa and < 20.0 kPa.
- Subjects on non-insulin dependent diabetic, weight loss, or lipid-modifying medication(s) must be on stable dose(s) for at least 3 months prior to the diagnostic liver biopsy through randomization.
- Subjects on vitamin E and pioglitazone must maintain a stable dosage before the diagnostic liver biopsy and during the study period.
Who cannot join
- 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.
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- 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.
- Subjects with a history of (12 months prior to baseline) or current use of prescription drugs associated with liver steatosis (e.g., methotrexate, amiodarone, high-dose estrogen, tamoxifen, systemic steroids, anabolic steroids, valproic acid) should be excluded. However, subjects currently using silymarin should maintain their current dosage throughout the trial period.
- Contraindication of magnetic resonance imaging. These include but are not limited to devices or metal foreign bodies, such as Pacemaker, defibrillator or wires other than sternal wires, metallic foreign body in the eye, "triggerfish" contact lens, gastric reflux device, and insulin pumps.
- MELD score >12
- Subjects with esophageal or gastric varices with recent bleeding episodes (within 1 year).
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Taiwan10 sites, 10 recruiting
- Recruiting
Ditmanson Medical Foundation Chiayi Christian Hospital；Chiayi Christian Hospital (CYCH)
Chiayi City, Taiwan, 600566
Perry Weng, 886-5-276-5041 ext. 2535, cych06629@gmail.com
- Recruiting
Kaohsiung Medical University Chung-Ho Memorial Hospital(KMUH)
Kaohsiung, Taiwan, 807
Feng Yufeng, 886-7-312-1101 ext. 6770, fatfat0520@gmail.com
- Recruiting
E-Da Hospital (EDH)
Kaohsiung, Taiwan, 824
Chih-Wen Lin, 886-7-6150011 ext. 251179, lincw66@gmail.com
- Recruiting
Chang Gung Medical Foundation-Kaohsiung (CGMF-KS)
Kaohsiung, Taiwan, 833
Sheng-Nan Lu, 886-7-7317123 ext. 6161, juten@ms17.hinet.net
- Recruiting
Chang Gung Medical Foundation-Keelung (CGMF-KL)
Keelung, Taiwan, 204
Li-Wen Chen, 886-2-24313131 ext. 6203, leiwei@cgmh.org.tw
- Recruiting
National Cheng Kung University Hospital (NCKUH)
Tainan, Taiwan, 704
Ying Ru Lu, 886-6-2353535 ext. 4220, ruby10808076@gmail.com
- Recruiting
National Taiwan University Hospital (NTUH)
Taipei, Taiwan, 100229
Chun-Hui Fu, +886-2-23123456 ext. 66384, jiun0924@gmail.com
- Recruiting
Taipei Veterans General Hospital (TPVGH)
Taipei, Taiwan, 112201
Ying-Luan Wang, 886-958661767, ine0213@yahoo.com.tw
- Recruiting
Fu Jen Catholic University Hospital (FJCUH)
Taipei, Taiwan, 243
Chi-Yang Chang, 886-2-85128888 ext. 28880, chiyang1112@gmail.com
- Recruiting
Chang Gung Medical Foundation-Linkou (CGMF-LK)
Taoyuan, Taiwan, 333
Chau-Ting Yeh, 886-3-3281200 ext. 8121, chauting@cgmh.org.tw
About this study
Official title: A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial of ADI-PEG 20 or Placebo in Subjects With Nonalcoholic Steatohepatitis (NASH)
Evaluate efficacy and safety of ADI-PEG 20 in patients with NASH
Read the detailed description
The safety of ADI-PEG 20 will be assessed during the study through the reporting of adverse events (AEs), clinical laboratory tests, electrocardiogram (ECG), vital sign assessments, body weight, and concomitant medication usage.
An external Data Safety and Monitoring Committee (DSMB) that consists of two hepatologists and a statistician will review the safety of the study. The DSMB will convene after 10 subjects (approximately 5 per treatment group) have completed the Week 4 assessments. The DSMB will receive all reports of serious adverse events (SAEs) and convene as needed to monitor for safety.
The primary efficacy will be assessed via the absolute change from baseline in hepatic fat fraction measured by MRI-PDFF at Week 24.
- Conditions
- Nonalcoholic Steatohepatitis (NASH)
- Being tested
- ADI-PEG20, Placebo
- Keywords
- Nonalcoholic Steatohepatitis (NASH), Arginine, Arginine Deiminase, ADI-PEG 20, Pegargiminase
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG20Drug
Also called Pegargiminase
Treatment for NASH
PlaceboOther
Treatment for NASH
| Study group | Role | What they receive |
|---|---|---|
| Drug: ADI-PEG 20 | Experimental | Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Receives: Drug: ADI-PEG20 |
| Drug: Placebo | Placebo comparator | Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Evaluate percent change from baseline in hepatic fat fraction assessed by MRI-PDFF at Week 24
Measured: 24 Weeks
Assess the safety of ADI-PEG 20 in subjects with NASH
Evaluate the change from baseline in ALT at Weeks 12 and 24.
Measured: 24 Weeks
Assess the safety and tolerability of ADI-PEG 20 in subjects with NASH
Laboratory tests and clinical adverse events
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start13 Sep 2023
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonalcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- To evaluate efficacy and safety of ADI-PEG 20 or Placebo in patients with NASH
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Polaris Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John S Bomalaski, Study director, Polaris Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05842512
- Sponsor's protocol ID
- POLARIS2023-001
- Status last verified
- Sep 2025
- First submitted
- 20 Jan 2023
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No