A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT05569759|
Recruitment Status : Recruiting
First Posted : October 6, 2022
Last Update Posted : January 18, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Autoimmune Hepatitis||Drug: zetomipzomib Drug: placebo||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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.
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.
Subcutaneous injection of placebo
Other Name: sterile water for injection
- 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.
- 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.
- Alanine aminotransferase (ALT) [ Time Frame: Week 24 ]Mean changes from baseline in alanine aminotransferase (ALT)
- Partial Remission [ Time Frame: Week 24 ]Proportion of patients who achieve a partial remission (PR)
- Time to complete remission [ Time Frame: Baseline through Week 24 ]Time to complete remission (CR)
- Time to partial remission [ Time Frame: Baseline through Week 24 ]Time to partial remission (PR)
- Plasma concentrations of zetomipzomib and its metabolites [ Time Frame: Baseline through Week 16 ]Maximum plasma concentration [Cmax]
- Plasma concentrations of zetomipzomib and its metabolites [ Time Frame: Baseline through Week 16 ]Time of maximum plasma concentration [Tmax]
- Plasma concentrations of zetomipzomib and its metabolites [ Time Frame: Baseline through Week 16 ]Area under the concentration-time curve [AUC]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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.
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
|Contact: Kezar Life Sciences, Inc.||(650) email@example.com|
|Contact: Li Long, MDfirstname.lastname@example.org|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|Contact: Craig Lammert, MD|
|Principal Investigator:||Craig Lammert, MD||Indiana University Hospital|
|Principal Investigator:||Paul Martin||University of Miami|
|Responsible Party:||Kezar Life Sciences, Inc.|
|Other Study ID Numbers:||
|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|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
selective proteasome inhibition
ALT (alanine aminotransferase)
AST (aspartate aminotransferase)
Digestive System Diseases
Hepatitis, Viral, Human
RNA Virus Infections
Immune System Diseases