Autoimmune HepatitisPhase 2NCT05569759
A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)
A Phase 2 study testing zetomipzomib and zetomipzomib in open-label extension in people with Autoimmune Hepatitis, run by Kezar Life Sciences, Inc. at 24 sites in United States.
Trial summary
This was a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis received zetomipzomib or placebo in addition to standard-of-care for 24 weeks; an optional open-label extension period allowed participants to receive zetomipzomib (KZR-616) for an additional 24 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Hepatitis
- What is being tested?
- zetomipzomib and zetomipzomib in open-label extension
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 24 sitesUnited States
- Study dates
- 23 May 2023to 30 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 or continue to taper glucocorticoid therapy.
Who cannot join
- Same as Double-blind Treatment Period except no need to re-test for HIV, HBV, HCV, and TB.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
University of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Northwestern University
Chicago, Illinois, 60611
Rush University
Chicago, Illinois, 60612
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Duke University Medical Center
Durham, North Carolina, 27710
Indiana University
Indianapolis, Indiana, 46202
Mayo Clinic Florida
Jacksonville, Florida, 32224
Keck School of Medicine of USC
Los Angeles, California, 90033
University of California, Los Angeles
Los Angeles, California, 90095
Northwell Health Center for Liver Disease and Transplantation
Manhasset, New York, 11030
University of Miami
Miami, Florida, 33136
Yale University
New Haven, Connecticut, 06510
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
New York University Langone Health/Grossman School of Medicine
New York, New York, 10016
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Stanford Medicine
Redwood City, California, 94063
Virginia Commonwealth University
Richmond, Virginia, 23298
California Pacific Medical Center
San Francisco, California, 94109
University of California, San Francisco
San Francisco, California, 94132
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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
This was a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis received zetomipzomib or placebo in addition to standard-of-care for 24 weeks; an optional open-label extension period allowed participants to receive zetomipzomib (KZR-616) for an additional 24 weeks of treatment.
Read the detailed description
This was 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 were 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 was administered subcutaneously (SC) once weekly.
At the end of the 24-week treatment period, eligible participants from both the zetomipzomib- and placebo-treated arms who completed the double-blind treatment period could enroll in the open-label extension period to receive up to an additional 24 weeks of treatment with zetomipzomib.
- Conditions
- Autoimmune Hepatitis
- Being tested
- zetomipzomib, placebo, zetomipzomib in open-label extension
- Keywords
- immunoproteasome inhibition, selective proteasome inhibition, disease flare, liver enzymes, ALT (alanine aminotransferase), AST (aspartate aminotransferase), glucocorticoids, steroids
- Medical subject headings
- Hepatitis, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zetomipzomibDrug
Also called KZR-616
Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
placeboDrug
Also called sterile water for injection
Subcutaneous injection of placebo
zetomipzomib in open-label extensionDrug
Also called KZR-616
Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
| Study group | Role | What they receive |
|---|---|---|
| zetomipzomib + standard-of-care (glucocorticoids) | Experimental | Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period. Receives: Drug: zetomipzomib |
| placebo + standard-of-care (glucocorticoids) | Placebo comparator | 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. Receives: Drug: placebo |
| zetomipzomib + standard-of care (glucocorticoids) open-label extension period | Experimental | 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 up to a total of 24 additional weeks of treatment. Receives: Drug: zetomipzomib in open-label extension |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients Who Achieved Complete Biochemical Response
The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.
Measured: Week 12, Week 16, Week 20, and Week 24
The Safety and Tolerability of Zetomipzomib
Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).
Measured: Baseline through end of study visit (DBTP, Week 28 and OLE, Up to Week 24)
Proportion of Participants Experiencing a Disease Flare Among the Participants Who Achieved a CR During the Double-blind Treatment Period
Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.
Measured: Start of open-label extension (OLE) period through End of Study (EOS) up to OLE Week 25
Secondary outcomes (11)
Alanine Aminotransferase (ALT)
Changes from baseline in alanine aminotransferase (ALT) during the double-blind treatment period.
Measured: Weeks 12, 16, 20, and 24
Partial Response
Proportion of participants who achieved a partial response (PR) during the double-blind treatment period of the study.
Measured: Weeks 12, 16, 20, and 24
Time to Complete Response
Time to complete response (CR), defined as the duration from first dose of study drug (zetomipzomib or placebo) to first CR, during the double-blind treatment period was measured using the Kaplan-Meier method. Due to the small sample size, not enough events of participants achieving CR were observed to provide Kaplan-Meier estimates for the 25th percentile, median, and 75th percentile time to CR.
Measured: Baseline through Week 24
Disease Flare After CR
Proportion of participants who experienced a disease flare after complete response (CR) during the double-blind treatment period.
Measured: Week 24
Treatment Failures
Proportion of participants who were considered treatment failures, defined as ALT or AST level worsened ≥2 times that of the Baseline value that is sustained for ≥1 week as verified via repeat laboratory assessments, despite compliance with standard of care (ie, with regard to inclusion criteria) or protocol-defined therapy or a glucocorticoid dose is increased above the Baseline dose, it may be considered a treatment failure unless attributed to an adverse event not relating to AIH, during the double-blind treatment period.
Measured: Week 24
Complete Response With Glucocorticoid Taper to ≤10 mg
Percentage of participants who achieved complete response with successful glucocorticoid taper to ≤10 mg by Week 24 of the double-blind treatment period.
Measured: Weeks 12, 16, 20, and 24
Complete Response With Glucocorticoid Taper to ≤5 mg
Percentage of participants who achieved complete response and glucocorticoid taper to ≤5 mg by Week 24 of the double-blind treatment period.
Measured: Weeks 12, 16, 20, and 24
Complete Response With Glucocorticoid Taper to 0 mg
Percentage of participants who achieved complete response with glucocorticoid taper to 0 mg by Week 24 of the double-blind treatment period.
Measured: Weeks 12, 16, 20, and 24
Partial Response With Glucocorticoid Taper to ≤10 mg
Percentage of participants who achieved partial response with successful glucocorticoid taper to ≤10 mg by Week 24 of the double-blind treatment period.
Measured: Week 24
Partial Response With Glucocorticoid Taper to ≤5 mg
Percentage of participants who achieved partial response and glucocorticoid taper to ≤5 mg by Week 24 of the double-blind treatment period.
Measured: Week 24
Partial Response With Glucocorticoid Taper to 0 mg
Percentage of participants who achieved partial response with glucocorticoid taper to 0 mg by Week 24 of the double-blind treatment period.
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2022
- Study start23 May 2023
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Autoimmune HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kezar Life Sciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Craig Lammert, MD, Principal investigator, Indiana UniversityEthan Weinberg, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05569759
- Sponsor's protocol ID
- KZR-616-208
- Status last verified
- Dec 2025
- First submitted
- 29 Sep 2022
- Last updated
- 13 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05569759
- Acronym / sponsor ID
- KZR-616-208
- Conditions
- Autoimmune Hepatitis
- Keywords
- immunoproteasome inhibition, selective proteasome inhibition, disease flare, liver enzymes, ALT (alanine aminotransferase), AST (aspartate aminotransferase), glucocorticoids, steroids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Kezar Life Sciences, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 May 2023 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 6 Oct 2022 (actual)
- Results
- Posted 13 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis received zetomipzomib or placebo in addition to standard-of-care for 24 weeks; an optional open-label extension period allowed participants to receive zetomipzomib (KZR-616) for an additional 24 weeks of treatment.
Detailed description
This was 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 were 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 was administered subcutaneously (SC) once weekly.
At the end of the 24-week treatment period, eligible participants from both the zetomipzomib- and placebo-treated arms who completed the double-blind treatment period could enroll in the open-label extension period to receive up to an additional 24 weeks of treatment with zetomipzomib.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| zetomipzomib + standard-of-care (glucocorticoids) | Experimental | Drug: zetomipzomibInitial 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 comparator | Drug: placeboInitial 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 | Experimental | Drug: zetomipzomib in open-label extensionInitial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Same as Double-blind Treatment Period inclusion criteria, except the following modifications:
- 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 or continue to taper glucocorticoid therapy.
Key exclusion criteria (1 listed)
- Same as Double-blind Treatment Period except no need to re-test for HIV, HBV, HCV, and TB.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zetomipzomibAlso: KZR-616Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly | Drug | zetomipzomib + standard-of-care (glucocorticoids) |
| placeboAlso: sterile water for injectionSubcutaneous injection of placebo | Drug | placebo + standard-of-care (glucocorticoids) |
| zetomipzomib in open-label extensionAlso: KZR-616Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly | Drug | zetomipzomib + standard-of care (glucocorticoids) open-label extension period |
Primary outcome
Patients Who Achieved Complete Biochemical Response
Time frame: Week 12, Week 16, Week 20, and Week 24
The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.
The Safety and Tolerability of Zetomipzomib
Time frame: Baseline through end of study visit (DBTP, Week 28 and OLE, Up to Week 24)
Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).
Proportion of Participants Experiencing a Disease Flare Among the Participants Who Achieved a CR During the Double-blind Treatment Period
Time frame: Start of open-label extension (OLE) period through End of Study (EOS) up to OLE Week 25
Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.
11 secondary outcomes
Alanine Aminotransferase (ALT)
Time frame: Weeks 12, 16, 20, and 24
Partial Response
Time frame: Weeks 12, 16, 20, and 24
Time to Complete Response
Time frame: Baseline through Week 24
Disease Flare After CR
Time frame: Week 24
Treatment Failures
Time frame: Week 24
Complete Response With Glucocorticoid Taper to ≤10 mg
Time frame: Weeks 12, 16, 20, and 24
Complete Response With Glucocorticoid Taper to ≤5 mg
Time frame: Weeks 12, 16, 20, and 24
Complete Response With Glucocorticoid Taper to 0 mg
Time frame: Weeks 12, 16, 20, and 24
Partial Response With Glucocorticoid Taper to ≤10 mg
Time frame: Week 24
Partial Response With Glucocorticoid Taper to ≤5 mg
Time frame: Week 24
Partial Response With Glucocorticoid Taper to 0 mg
Time frame: Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Corporate websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Lammert, MD principal investigator
Indiana University
Ethan Weinberg, MD principal investigator
University of Pennsylvania
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing zetomipzomib and zetomipzomib in open-label extension in people with Autoimmune Hepatitis, run by Kezar Life Sciences, Inc. at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients Who Achieved Complete Biochemical Response (time frame: Week 12, Week 16, Week 20, and Week 24). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.