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

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ClinicalTrials.gov Identifier: NCT05569759
Recruitment Status : Recruiting
First Posted : October 6, 2022
Last Update Posted : January 18, 2023
Sponsor:
Information provided by (Responsible Party):
Kezar Life Sciences, Inc.

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : January 2023
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: sterile water for injection


Outcome Measures
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Primary Outcome Measures :
  1. To evaluate the efficacy of zetomipzomib [ Time Frame: Week 24 ]
    Proportion of patients who achieve complete biochemical remission (CR) with successful glucocorticoid taper by Week 24.

  2. To evaluate the safety and tolerability of zetomipzomib [ Time Frame: 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 :
  1. Alanine aminotransferase (ALT) [ Time Frame: Week 24 ]
    Mean changes from baseline in alanine aminotransferase (ALT)

  2. Partial Remission [ Time Frame: Week 24 ]
    Proportion of patients who achieve a partial remission (PR)

  3. Time to complete remission [ Time Frame: Baseline through Week 24 ]
    Time to complete remission (CR)

  4. Time to partial remission [ Time Frame: Baseline through Week 24 ]
    Time to partial remission (PR)


Other Outcome Measures:
  1. Plasma concentrations of zetomipzomib and its metabolites [ Time Frame: Baseline through Week 16 ]
    Maximum plasma concentration [Cmax]

  2. Plasma concentrations of zetomipzomib and its metabolites [ Time Frame: Baseline through Week 16 ]
    Time of maximum plasma concentration [Tmax]

  3. Plasma concentrations of zetomipzomib and its metabolites [ Time Frame: Baseline through Week 16 ]
    Area under the concentration-time curve [AUC]


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05569759


Contacts
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Contact: Kezar Life Sciences, Inc. (650) 822-5600 clinicaltrials@kezarbio.com
Contact: Li Long, MD llong@kezarbio.com

Locations
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United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Craig Lammert, MD         
Sponsors and Collaborators
Kezar Life Sciences, Inc.
Investigators
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Principal Investigator: Craig Lammert, MD Indiana University Hospital
Principal Investigator: Paul Martin University of Miami
More Information
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Additional Information:

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Responsible Party: Kezar Life Sciences, Inc.
ClinicalTrials.gov Identifier: NCT05569759    
Other Study ID Numbers: KZR-616-208
First Posted: October 6, 2022    Key Record Dates
Last Update Posted: January 18, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kezar Life Sciences, Inc.:
immunoproteasome inhibition
selective proteasome inhibition
disease flare
Liver enzymes
 ALT (alanine aminotransferase)
AST (aspartate aminotransferase)
glucocorticoids
steroids
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis
Hepatitis, Autoimmune
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
 Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepatitis, Chronic
Autoimmune Diseases
Immune System Diseases