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

Sponsor

Kezar Life Sciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05569759

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Hepatitis	Drug: zetomipzomib Drug: placebo	Phase 2

Detailed Description

This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Phase 2a Study to Evaluate the Safety and Efficacy of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: zetomibzomib + 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.	Drug: zetomipzomib Subcutaneous injection of zetomipzomib
Placebo Comparator: 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.	Drug: placebo Subcutaneous injection of placebo Other Names: sterile water for injection

Arm

Intervention/Treatment

Experimental: zetomibzomib + 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.

Drug: zetomipzomib

Subcutaneous injection of zetomipzomib

Placebo Comparator: 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.

Drug: placebo

Subcutaneous injection of placebo

Other Names:

sterile water for injection

Outcome Measures

Primary Outcome Measures

To evaluate the efficacy of zetomipzomib [Week 24]
Proportion of patients who achieve complete biochemical remission (CR) with successful glucocorticoid taper 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.

Secondary Outcome Measures

Alanine aminotransferase (ALT) [Week 24]
Mean changes from baseline in alanine aminotransferase (ALT)
Partial Remission [Week 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)

Other Outcome Measures

Plasma concentrations of zetomipzomib and its metabolites [Baseline through Week 16]
Maximum plasma concentration [Cmax]
Plasma concentrations of zetomipzomib and its metabolites [Baseline through Week 16]
Time of maximum plasma concentration [Tmax]
Plasma concentrations of zetomipzomib and its metabolites [Baseline through Week 16]
Area under the concentration-time curve [AUC]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.