A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)
Autoimmune Hepatitis
About this trial
This is an interventional treatment trial for Autoimmune Hepatitis focused on measuring immunoproteasome inhibition, selective proteasome inhibition, disease flare, Liver enzymes, ALT (alanine aminotransferase), AST (aspartate aminotransferase), glucocorticoids, steroids
Eligibility Criteria
Key Inclusion Criteria:
Must be aged ≥18 years.
Must have a clinical diagnosis of AIH and signs of active disease or disease flare despite standard-of-care therapy for ≥3 months, including:
- Screening ALT values that are 1.25 to 10 times the upper limit of the normal range (ULN)
- Liver biopsy results with Ishak score (modified HAI) ≥5/18 indicating active AIH, from a biopsy performed at Screening, or within 6 months prior to Screening
- Mild or no hepatic impairment (Child Pugh category A)
- Must be willing to use and taper glucocorticoid therapy.
Key Exclusion Criteria:
- Have a concomitant diagnosis of primary biliary sclerosis, primary sclerosing cholangitis, IgG 4 related cholangitis, drug related AIH (at Screening) or a history of drug-related AIH.
- Are receiving oral or injectable immunomodulating treatment for any other autoimmune disease prior to enrollment in the study. Patients who have been using such treatments must follow the specified washout periods.
- Have an active infection (eg, acute hepatitis E, cytomegalovirus, or Epstein-Barr virus) requiring systemic therapy with antibiotic, antiviral, or antifungal treatment, or has had any febrile illness within 7 days prior to Day -1.
- Have a history of thyroiditis, celiac disease, or other autoimmune disorder known to be associated with transaminitis.
- Have liver cirrhosis with significant impairment of liver function (Child Pugh category B or C) or have decompensated cirrhosis.
- Patients with histology confirmed coincident non-alcoholic steatohepatitis.
Sites / Locations
- Mayo Clinic ArizonaRecruiting
- Keck School of Medicine of USCRecruiting
- University of California, Los AngelesRecruiting
- Stanford MedicineRecruiting
- California Pacific Medical CenterRecruiting
- University of ColoradoRecruiting
- Mayo Clinic FloridaRecruiting
- University of MiamiRecruiting
- Northwestern UniversityRecruiting
- Rush UniversityRecruiting
- Indiana UniversityRecruiting
- Ochsner Clinic FoundationRecruiting
- Massachusetts General HospitalRecruiting
- Beth Israel Deaconess Medical CenterRecruiting
- University of Michigan Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- New York University Langone Health/Grossman School of MedicineRecruiting
- University Hospitals Cleveland Medical CenterRecruiting
- University of PennsylvaniaRecruiting
- Virginia Commonwealth UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Placebo Comparator
Experimental
zetomibzomib + standard-of-care (glucocorticoids)
placebo + standard-of-care (glucocorticoids)
zetomipzomib + standard-of care (glucocorticoids) open-label extension period
Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period.
Initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period.
Initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for a total of 24 additional weeks of treatment.