Phase 2
N=24
A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)
Autoimmune Hepatitis
Bottom Line
View on ClinicalTrials.gov: NCT05569759 ↗Enrolled (actual)
24
Serious AEs
8.1%
Results posted
Jan 2026
Primary outcome: Primary: Patients Who Achieved Complete Biochemical Response — 6; 3; 7; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- zetomipzomib (Drug); placebo (Drug); zetomipzomib in open-label extension (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kezar Life Sciences, Inc.
- Primary completion
- Apr 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Patients Who Achieved Complete Biochemical Response |
6; 3; 7; 3; 8; 3 | — |
| PRIMARY The Safety and Tolerability of Zetomipzomib |
2; 1; 0; 0; 16; 7 | — |
| PRIMARY Proportion of Participants Experiencing a Disease Flare Among the Participants Who Achieved a CR During the Double-blind Treatment Period |
0; 0 | — |
| SECONDARY Alanine Aminotransferase (ALT) |
-49.8; -47.3; -46.4; -65.8; -29.4; -33.3 | — |
| SECONDARY Partial Response |
4; 2; 1; 0; 1; 0 | — |
| SECONDARY Time to Complete Response |
NA; NA | — |
| SECONDARY Disease Flare After CR |
0; 0 | — |
| SECONDARY Treatment Failures |
2; 1 | — |
| SECONDARY Complete Response With Glucocorticoid Taper to ≤10 mg |
18.8; 25.0; 37.5; 25.0; 43.8; 25.0 | — |
| SECONDARY Complete Response With Glucocorticoid Taper to ≤5 mg |
12.5; 0; 25.0; 12.5; 37.5; 12.5 | — |
| SECONDARY Complete Response With Glucocorticoid Taper to 0 mg |
6.3; 0; 6.3; 0; 12.5; 0 | — |
| SECONDARY Partial Response With Glucocorticoid Taper to ≤10 mg |
31.3; 25.0 | — |
| SECONDARY Partial Response With Glucocorticoid Taper to ≤5 mg |
12.5; 12.5 | — |
| SECONDARY Partial Response With Glucocorticoid Taper to 0 mg |
12.5; 0 | — |
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.
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 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.
Data sourced from ClinicalTrials.gov (NCT05569759). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.