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

Autoimmune Hepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05569759
• Other study ID #: KZR-616-208
• Status: Recruiting
• Phase: Phase 2
• Start date: May 23, 2023
• Est. completion date: March 2025

Study information

• Verified date: December 2023
• Source: Kezar Life Sciences, Inc.
• Contact: Kezar Life Sciences, Inc.
• Phone: (650) 822-5600
• Email: PORTOLA[@]kezarbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: March 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria for the Double-blind Treatment Period:

• 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.

Key Exclusion Criteria for the Double-blind Treatment Period:

• 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.

Key Inclusion Criteria for the Open-label Extension Period:

• Same as Double-blind Treatment Period inclusion criteria, except the following modifications:

• 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 at 5 mg/day or continue to taper glucocorticoid therapy.

Key Exclusion Criteria for the Open-label Extension Period:

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

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Autoimmune

Intervention

Drug:
• zetomipzomib
Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
• placebo
Subcutaneous injection of placebo
• zetomipzomib in open-label extension
Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Rush University	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Indiana University	Indianapolis	Indiana
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Keck School of Medicine of USC	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Northwell Health Center for Liver Disease and Transplantation	Manhasset	New York
United States	University of Miami	Miami	Florida
United States	Yale University	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	New York University Langone Health/Grossman School of Medicine	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Stanford Medicine	Redwood City	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	California Pacific Medical Center	San Francisco	California
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Kezar Life Sciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma concentrations of zetomipzomib and its metabolites	Maximum plasma concentration [Cmax]	Baseline through Week 16
Other	Plasma concentrations of zetomipzomib and its metabolites	Time of maximum plasma concentration [Tmax]	Baseline through Week 16
Other	Plasma concentrations of zetomipzomib and its metabolites	Area under the concentration-time curve [AUC]	Baseline through Week 16
Primary	To evaluate the efficacy of zetomipzomib	Proportion of patients who achieve complete biochemical remission (CR) with successful glucocorticoid taper by Week 24.	Week 24
Primary	To evaluate the safety and tolerability of zetomipzomib	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.	Baseline through 28 weeks.
Primary	To evaluate the efficacy of zetomipzomib during the open-label extension period	Proportion of patients experiencing a disease flare among the patients who achieved a complete biochemical remission (CR) during the double-blind treatment period.	Start of open-label extension (OLE) period through End of Study (EOS) at OLE Week 29
Secondary	Alanine aminotransferase (ALT)	Mean changes from baseline in alanine aminotransferase (ALT)	Week 24
Secondary	Partial Remission	Proportion of patients who achieve a partial remission (PR)	Week 24
Secondary	Time to complete remission	Time to complete remission (CR)	Baseline through Week 24
Secondary	Time to partial remission	Time to partial remission (PR)	Baseline through Week 24

External Links

•   Corporate website