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

April 9, 2024 updated by: Polaris Group

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Taiwan
      • Chiayi City, Taiwan, 600566
        • Not yet recruiting
        • Ditmanson Medical Foundation Chiayi Christian Hospital；Chiayi Christian Hospital (CYCH)
        • Contact:
      • Kaohsiung, Taiwan, 807
        • Not yet recruiting
        • Kaohsiung Medical University Chung-Ho Memorial Hospital(KMUH)
        • Contact:
      • Kaohsiung, Taiwan, 824
        • Not yet recruiting
        • E-Da Hospital (EDH)
        • Contact:
      • Kaohsiung, Taiwan, 833
        • Recruiting
        • Chang Gung Medical Foundation-Kaohsiung (CGMF-KS)
        • Contact:
      • Keelung, Taiwan, 204
        • Recruiting
        • Chang Gung Medical Foundation-Keelung (CGMF-KL)
        • Contact:
      • Tainan, Taiwan, 704
        • Not yet recruiting
        • National Cheng Kung University Hospital (NCKUH)
        • Contact:
      • Taipei, Taiwan, 100229
        • Not yet recruiting
        • National Taiwan University Hospital (NTUH)
        • Contact:
      • Taipei, Taiwan, 112201
        • Not yet recruiting
        • Taipei Veterans General Hospital (TPVGH)
        • Contact:
      • Taipei City, Taiwan, 243
        • Recruiting
        • Fu Jen Catholic University Hospital (FJCUH)
        • Contact:
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Chang Gung Medical Foundation-Linkou (CGMF-LK)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Males and non-lactating, pregnancy test negative females between 18 - 80 years of age with biopsy proven F1 - F3 NASH. Limit F1 fibrosis to ≤ 20% of total subject population.
  2. Willingness to use appropriate contraceptive measures though out study treatment and for 90 days thereafter (see Appendix A).
  3. Body mass index (BMI) > 25 kg/m2
  4. Must have confirmation of ≥ 10% liver fat content on MRI-PDFF at screening.

  5. Biopsy-proven NASH. Must have had a liver biopsy within 4 weeks of randomization with fibrosis stage 1 to 3 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:

    1. Steatosis (scored 0 to 3),
    2. Ballooning degeneration (scored 0 to 2), and
    3. Lobular inflammation (scored 0 to 3).
  6. Must have no evidence of worsening of ALT and AST (within 50%) measurements at the screening (-4 weeks) and pre-baseline (-2 weeks) visits.

  7. Screening laboratory parameters, as determined by the central laboratory:

    1. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft- Gault equation;
    2. HbA1c ≤ 9.5% (or serum fructosamine ≤ 381 µmol if HbA1c is unable to be resulted);
    3. Hemoglobin ≥ 11 g/dL;
    4. INR ≤ 1.3, unless due to therapeutic anticoagulation;
    5. Direct bilirubin ≤ 0.5 mg/dL;
    6. Total bilirubin ≤ 1.3 x upper limit of normal (ULN), unless due to an alternate etiology such as Gilbert's syndrome or hemolytic anemia;
    7. Creatinine kinase < 3 x ULN;
    8. Platelet count ≥ 150,000/µL;
    9. Serum triglyceride level ≤ 500 mg/dL;
    10. ALT < 5 x ULN;
    11. AST < 5 x ULN;
    12. ALP < 2 x ULN.
  8. FibroScan® measurement > 7.0 kPa
  9. 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.

Exclusion Criteria:

  1. Weight gain or loss > 5% in the 3 months prior to randomization or > 10% in the 6 months prior to screening.
  2. Type 1 and insulin-dependent Type 2 diabetes.
  3. Presence of cirrhosis on liver biopsy (stage 4 fibrosis).
  4. Poorly controlled hypertension (blood pressure [BP] > 160/100 mmHg).
  5. Prior history of decompensated liver disease including ascites, hepatic encephalopathy (HE), or variceal bleeding.
  6. Chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg] positive).
  7. Chronic hepatitis C virus (HCV) infection (HCV antibody [Ab] and HCV ribonucleic acid [RNA] positive). Subjects cured of HCV infection less than 2 years prior (based on date of RNA polymerase chain reaction [PCR] negative confirmation following conclusion of treatment) to the screening visit are not eligible.
  8. 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.
  9. 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.
  10. History of liver transplantation.
  11. Current or prior history of hepatocellular carcinoma (HCC).
  12. Alcohol intake above an average limit of 2 drinks per day for women and 3 drinks per day for men.
  13. Human immunodeficiency virus (HIV) infection.
  14. Unstable cardiovascular disease in the 6 months prior to screening.
  15. Life expectancy less than 2 years.
  16. 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.
  17. Subjects with a history of (12 months prior to screening) 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug: ADI-PEG 20
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)
Drug: ADI-PEG20
Treatment for NASH
Other Names:
  • Pegargiminase
Placebo Comparator: Drug: Placebo
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)
Other: Placebo
Treatment for NASH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine Efficacy of ADI-PEG 20 vs Placebo in the treatment of fatty liver as assessed by change in hepatic fat fraction
Time Frame: 24 Weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the Efficacy of ADI-PEG 20 vs Placebo reflected in the percent change from baseline in hepatic fat fraction at week 24
Time Frame: 24 Weeks
Evaluate percent change from baseline in hepatic fat fraction assessed by MRI-PDFF at Week 24
24 Weeks
Assess the safety of ADI-PEG 20 in subjects with NASH
Time Frame: 24 Weeks
Evaluate the change from baseline in ALT at Weeks 12 and 24.
24 Weeks
Assess the safety and tolerability of ADI-PEG 20 in subjects with NASH
Time Frame: 24 Weeks
Laboratory tests and clinical adverse events
24 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Polaris Group

Investigators

  • Study Director: John S Bomalaski, Polaris Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 13, 2023

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

January 31, 2028

Study Registration Dates

First Submitted

January 20, 2023

First Submitted That Met QC Criteria

April 24, 2023

First Posted (Actual)

May 6, 2023

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 9, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • POLARIS2023-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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