A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)

NCT ID: NCT05569759

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-23
• Study Completion Date: 2025-04-30

Brief Summary

This was a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis received zetomipzomib or placebo in addition to standard-of-care for 24 weeks; an optional open-label extension period allowed participants to receive zetomipzomib (KZR-616) for an additional 24 weeks of treatment.

Detailed Description

This was a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study with an open-label extension to evaluate safety, tolerability, and efficacy of zetomipzomib in patients with autoimmune hepatitis (AIH) who have not benefited from standard-of-care treatment, had an incomplete response to ≥3 months of standard-of-care treatment, or had a disease flare after standard of care.

Zetomipzomib or placebo were administered weekly for a 24-week treatment period in addition to standard-of-care (glucocorticoids), followed by a 4-week off-treatment safety follow-up period. Zetomipzomib and placebo was administered subcutaneously (SC) once weekly.

At the end of the 24-week treatment period, eligible participants from both the zetomipzomib- and placebo-treated arms who completed the double-blind treatment period could enroll in the open-label extension period to receive up to an additional 24 weeks of treatment with zetomipzomib.

Conditions

Autoimmune Hepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

zetomipzomib + standard-of-care (glucocorticoids)

Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period.

Group Type: EXPERIMENTAL

zetomipzomib

Intervention Type: DRUG

Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly

placebo + standard-of-care (glucocorticoids)

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Subcutaneous injection of placebo

zetomipzomib + standard-of care (glucocorticoids) open-label extension 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 up to a total of 24 additional weeks of treatment.

Group Type: EXPERIMENTAL

zetomipzomib in open-label extension

Intervention Type: DRUG

Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly

Interventions

zetomipzomib

Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly

Intervention Type: DRUG

placebo

Subcutaneous injection of placebo

Intervention Type: DRUG

zetomipzomib in open-label extension

Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly

Intervention Type: DRUG

Other Intervention Names

KZR-616; sterile water for injection; KZR-616

Eligibility Criteria

Inclusion Criteria

• Must be aged ≥18 years.

• Must have a clinical diagnosis of AIH and signs of active disease despite standard-of-care therapy for ≥3 months or disease flare after experiencing complete remission induced by standard-of-care treatment, 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.
• Must be willing to use effective contraception.

• ALT value can be normal or, if elevated, in the range of 1.25 to 10 times the upper limit of normal
• Must have completed the Double-blind Period study visits through Week 24, including all Week 24 Visit assessments.
• Must be willing to maintain glucocorticoid therapy or continue to taper glucocorticoid therapy.

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.
• Have clinical evidence of significant unstable or uncontrolled diseases other than the disease under study.
• 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.

• Same as Double-blind Treatment Period except no need to re-test for HIV, HBV, HCV, and TB.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kezar Life Sciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Lammert, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Ethan Weinberg, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Keck School of Medicine of USC

Los Angeles, California, United States

University of California, Los Angeles

Los Angeles, California, United States

Stanford Medicine

Redwood City, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of California, San Francisco

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Northwestern University

Chicago, Illinois, United States

Rush University

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Northwell Health Center for Liver Disease and Transplantation

Manhasset, New York, United States

New York University Langone Health/Grossman School of Medicine

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.kezarlifesciences.com

Corporate website

Other Identifiers

KZR-616-208

Identifier Type: -

Identifier Source: org_study_id