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

NCT05569759 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: KZR-616-208
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 24

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.

Conditions

Autoimmune Hepatitis

Keywords

immunoproteasome inhibition; selective proteasome inhibition; disease flare; liver enzymes; ALT (alanine aminotransferase); AST (aspartate aminotransferase); glucocorticoids; steroids

Outcome Measures

Primary Outcomes (3)

• Patients Who Achieved Complete Biochemical Response

  The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.

  Week 12, Week 16, Week 20, and Week 24

• The Safety and Tolerability of Zetomipzomib

  Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).

  Baseline through end of study visit (DBTP, Week 28 and OLE, Up to Week 24)

• Proportion of Participants Experiencing a Disease Flare Among the Participants Who Achieved a CR During the Double-blind Treatment Period

  Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.

  Start of open-label extension (OLE) period through End of Study (EOS) up to OLE Week 25

Secondary Outcomes (11)

• Alanine Aminotransferase (ALT)

  Weeks 12, 16, 20, and 24

• Partial Response

  Weeks 12, 16, 20, and 24

• Time to Complete Response

  Baseline through Week 24

• Disease Flare After CR

  Week 24

• Treatment Failures

  Week 24

Other Outcomes (1)

• Change From Baseline in Glucocorticoid Dose

  Weeks 12, 16, 20, and 24

Study Arms (3)

zetomipzomib + standard-of-care (glucocorticoids)

EXPERIMENTAL

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

Drug: zetomipzomib

placebo + standard-of-care (glucocorticoids)

PLACEBO COMPARATOR

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.

Drug: placebo

zetomipzomib + standard-of care (glucocorticoids) open-label extension period

EXPERIMENTAL

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.

Drug: zetomipzomib in open-label extension

Interventions

zetomipzomib DRUG

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

Also known as: KZR-616

zetomipzomib + standard-of-care (glucocorticoids)

placebo DRUG

Subcutaneous injection of placebo

Also known as: sterile water for injection

placebo + standard-of-care (glucocorticoids)

zetomipzomib in open-label extension DRUG

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

Also known as: KZR-616

zetomipzomib + standard-of care (glucocorticoids) open-label extension period

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Kezar Life Sciences, Inc.: lead

Study Sites (24)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford Medicine

Redwood City, California, 94063, United States

Location

California Pacific Medical Center

San Francisco, California, 94109, United States

Location

University of California, San Francisco

San Francisco, California, 94132, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Northwell Health Center for Liver Disease and Transplantation

Manhasset, New York, 11030, United States

Location

New York University Langone Health/Grossman School of Medicine

New York, New York, 10016, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Links

• Corporate website

MeSH Terms

Conditions

Hepatitis, Autoimmune

Interventions

KZR-616; Injections

Condition Hierarchy (Ancestors)

Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

Limitations of this study include its small sample size, unpowered design, and a predominantly white study population, which may limit generalizability.

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Kezar Life Sciences, Inc.

clinicaltrials@kezarbio.com

650-822-5600

Study Officials

• Craig Lammert, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Ethan Weinberg, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2022
• First Posted: October 6, 2022
• Study Start: May 23, 2023
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)