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

Phase 2

Completed

• Conditions: Autoimmune Hepatitis
• Interventions: Drug: zetomipzomib; Drug: placebo; Drug: zetomipzomib in open-label extension

• Registration Number: NCT05569759
• Lead Sponsor: Kezar Life Sciences, Inc.

Brief Summary

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

Detailed Description

This is 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 will be 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 will be administered subcutaneously (SC) once weekly.

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

Primary completion date represents the anticipated completion date of the double-blind portion of the study. Study completion date represents the anticipated completion date of the open-label extension portion of the study.

Study Timeline

• Study First Submitted: 2022-09-29
• Study First Submitted QC: 2022-10-03
• Study First Posted: 2022-10-06
• Study Start: 2023-05-23
• Status Verified: 2024-09
• Primary Completion: 2025-04-30
• Study Completion: 2025-04-30
• Last Update Submitted: 2025-05-28
• Last Update Posted: 2025-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
zetomipzomib + standard-of-care (glucocorticoids)	zetomipzomib	Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period.
placebo + standard-of-care (glucocorticoids)	placebo	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.
zetomipzomib + standard-of care (glucocorticoids) open-label extension period	zetomipzomib in open-label extension	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.

Primary Outcome Measures

Name	Time	Method
To evaluate the efficacy of zetomipzomib	Week 24	Proportion of patients who achieve complete biochemical remission (CR) by Week 24.
To evaluate the safety and tolerability of zetomipzomib	Baseline through 28 weeks.	Proportion of patients who experience AEs (adverse events) and SAEs (serious adverse events), including incidence and severity of AEs and SAEs, incidence of AEs leading to drug discontinuation, and changes in laboratory parameters and vital signs.
To evaluate the efficacy of zetomipzomib during the open-label extension period	Start of open-label extension (OLE) period through End of Study (EOS) at OLE Week 29	Proportion of patients experiencing a disease flare among the patients who achieved a complete biochemical remission (CR) during the double-blind treatment period.

Secondary Outcome Measures

Name	Time	Method
Partial Remission	Weeks 12, 16, 20, and 24	Proportion of patients who achieve a partial remission (PR)
Time to complete remission	Baseline through Week 24	Time to complete remission (CR)
Time to partial remission	Baseline through Week 24	Time to partial remission (PR)
Disease flare after CR	Week 24	Proportion of patients experiencing a disease flare after complete remission (CR)
Treatment failures	Week 24	Proportion of patients who are treatment failures
Successful glucocorticoid taper	Week 24	Proportion of patients who achieve CR or PR with successful glucocorticoid taper by Week 24
Alanine aminotransferase (ALT)	Weeks 12, 16, 20, and 24	Changes from baseline in alanine aminotransferase (ALT)

Trial Locations

Locations (24)

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

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