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

Primary Purpose

Autoimmune Hepatitis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
zetomipzomib
placebo
zetomipzomib in open-label extension
Sponsored by
Kezar Life Sciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoimmune Hepatitis focused on measuring immunoproteasome inhibition, selective proteasome inhibition, disease flare, Liver enzymes, ALT (alanine aminotransferase), AST (aspartate aminotransferase), glucocorticoids, steroids

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Mayo Clinic ArizonaRecruiting
  • Keck School of Medicine of USCRecruiting
  • University of California, Los AngelesRecruiting
  • Stanford MedicineRecruiting
  • California Pacific Medical CenterRecruiting
  • University of ColoradoRecruiting
  • Mayo Clinic FloridaRecruiting
  • University of MiamiRecruiting
  • Northwestern UniversityRecruiting
  • Rush UniversityRecruiting
  • Indiana UniversityRecruiting
  • Ochsner Clinic FoundationRecruiting
  • Massachusetts General HospitalRecruiting
  • Beth Israel Deaconess Medical CenterRecruiting
  • University of Michigan Medical CenterRecruiting
  • Washington University School of MedicineRecruiting
  • New York University Langone Health/Grossman School of MedicineRecruiting
  • University Hospitals Cleveland Medical CenterRecruiting
  • University of PennsylvaniaRecruiting
  • Virginia Commonwealth UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

zetomibzomib + standard-of-care (glucocorticoids)

placebo + standard-of-care (glucocorticoids)

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

Arm Description

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

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Alanine aminotransferase (ALT)
Mean changes from baseline in alanine aminotransferase (ALT)
Partial Remission
Proportion of patients who achieve a partial remission (PR)
Time to complete remission
Time to complete remission (CR)
Time to partial remission
Time to partial remission (PR)

Full Information

First Posted
September 29, 2022
Last Updated
October 20, 2023
Sponsor
Kezar Life Sciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05569759
Brief Title
A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2023 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kezar Life Sciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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; 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Hepatitis
Keywords
immunoproteasome inhibition, selective proteasome inhibition, disease flare, Liver enzymes, ALT (alanine aminotransferase), AST (aspartate aminotransferase), glucocorticoids, steroids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
zetomibzomib + standard-of-care (glucocorticoids)
Arm Type
Experimental
Arm Description
Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period.
Arm Title
placebo + standard-of-care (glucocorticoids)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
zetomipzomib + standard-of care (glucocorticoids) open-label extension period
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
zetomipzomib
Other Intervention Name(s)
KZR-616
Intervention Description
Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
sterile water for injection
Intervention Description
Subcutaneous injection of placebo
Intervention Type
Drug
Intervention Name(s)
zetomipzomib in open-label extension
Other Intervention Name(s)
KZR-616
Intervention Description
Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Primary Outcome Measure Information:
Title
To evaluate the efficacy of zetomipzomib
Description
Proportion of patients who achieve complete biochemical remission (CR) with successful glucocorticoid taper by Week 24.
Time Frame
Week 24
Title
To evaluate the safety and tolerability of zetomipzomib
Description
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.
Time Frame
Baseline through 28 weeks.
Title
To evaluate the efficacy of zetomipzomib during the open-label extension period
Description
Proportion of patients experiencing a disease flare among the patients who achieved a complete biochemical remission (CR) during the double-blind treatment period.
Time Frame
Start of open-label extension (OLE) period through End of Study (EOS) at OLE Week 29
Secondary Outcome Measure Information:
Title
Alanine aminotransferase (ALT)
Description
Mean changes from baseline in alanine aminotransferase (ALT)
Time Frame
Week 24
Title
Partial Remission
Description
Proportion of patients who achieve a partial remission (PR)
Time Frame
Week 24
Title
Time to complete remission
Description
Time to complete remission (CR)
Time Frame
Baseline through Week 24
Title
Time to partial remission
Description
Time to partial remission (PR)
Time Frame
Baseline through Week 24
Other Pre-specified Outcome Measures:
Title
Plasma concentrations of zetomipzomib and its metabolites
Description
Maximum plasma concentration [Cmax]
Time Frame
Baseline through Week 16
Title
Plasma concentrations of zetomipzomib and its metabolites
Description
Time of maximum plasma concentration [Tmax]
Time Frame
Baseline through Week 16
Title
Plasma concentrations of zetomipzomib and its metabolites
Description
Area under the concentration-time curve [AUC]
Time Frame
Baseline through Week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kezar Life Sciences, Inc.
Phone
(650) 822-5600
Email
PORTOLA@kezarbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig Lammert, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ethan Weinberg, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hugo Vargas, MD
First Name & Middle Initial & Last Name & Degree
Hugo Vargas, MD
Facility Name
Keck School of Medicine of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lily Dara, MD
First Name & Middle Initial & Last Name & Degree
Lily Dara, MD
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sammy Saab, MD
First Name & Middle Initial & Last Name & Degree
Sammy Saab, MD
Facility Name
Stanford Medicine
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aparna Goel, MD
First Name & Middle Initial & Last Name & Degree
Aparna Goel, MD
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kidist Yimam, MD
First Name & Middle Initial & Last Name & Degree
Kidist Yimam, MD
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Forman, MD
First Name & Middle Initial & Last Name & Degree
Lisa Forman, MD
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Surakit Pungpapong, MD
First Name & Middle Initial & Last Name & Degree
Surakit Pungpapong, MD
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Martin, MD
First Name & Middle Initial & Last Name & Degree
Paul Martin, MD
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Josh Levitsky, MD
First Name & Middle Initial & Last Name & Degree
Josh Levitksy, MD
Facility Name
Rush University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Flamm, MD
First Name & Middle Initial & Last Name & Degree
Steven Flamm, MD
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Craig Lammert, MD
First Name & Middle Initial & Last Name & Degree
Craig Lammert, MD
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Therapondos, MD
First Name & Middle Initial & Last Name & Degree
George Therapondos, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Pratt, MD
First Name & Middle Initial & Last Name & Degree
Daniel Pratt, MD
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vilas Patwardhan, MD
First Name & Middle Initial & Last Name & Degree
Vilas Patwardhan, MD
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Fontana, MD
First Name & Middle Initial & Last Name & Degree
Robert Fontana, MD
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin Korenblat, MD
First Name & Middle Initial & Last Name & Degree
Kevin Korenblat, MD
Facility Name
New York University Langone Health/Grossman School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raiya Sarwar, MD
First Name & Middle Initial & Last Name & Degree
Raiya Sarwar, MD
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seth Sclair, MD
First Name & Middle Initial & Last Name & Degree
Seth Sclair, MD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ethan Weinberg, MD
First Name & Middle Initial & Last Name & Degree
Ethan Weinberg, MD
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sayed Aseem, MD
First Name & Middle Initial & Last Name & Degree
Sayed Aseem, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.kezarlifesciences.com
Description
Corporate website

Learn more about this trial

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

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