Zetomipzomib for Autoimmune Hepatitis

No longer recruiting at 24 trial locations

Overseen By Li Long, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kezar Life Sciences, Inc.

Must be taking: Glucocorticoids

Must not be taking: Immunomodulators

Disqualifiers: Primary biliary sclerosis, Uncontrolled diseases, Active infection, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of zetomipzomib, a new treatment for autoimmune hepatitis, a condition where the immune system attacks the liver. Participants will receive either zetomipzomib or a placebo (a dummy treatment) alongside their regular treatment to assess disease management over 24 weeks. Individuals who have struggled with autoimmune hepatitis for at least three months may qualify. The trial also includes an option to continue zetomipzomib for another 24 weeks in an open-label extension, where all participants will know they are receiving the actual treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must be willing to taper glucocorticoid therapy. If you are on immunomodulating treatments for other autoimmune diseases, you must follow a washout period (time without taking those medications) before joining the study.

Is there any evidence suggesting that zetomipzomib is likely to be safe for humans?

Research has shown that zetomipzomib is generally safe and well-tolerated. In previous studies, most patients handled the treatment well, with few serious side effects reported. Evidence from these trials suggests that zetomipzomib is safe for humans. While no treatment is completely without risk, current findings reassure those considering participation in a trial with this medication. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autoimmune hepatitis?

Unlike the standard treatment for autoimmune hepatitis, which typically involves glucocorticoids, zetomipzomib offers a novel approach by using a different mechanism of action. This drug is a selective immunoproteasome inhibitor, which means it targets specific parts of the immune system involved in inflammation, potentially reducing side effects associated with traditional treatments. Researchers are excited because zetomipzomib could offer a more targeted therapy, bringing hope for better efficacy and safety in managing autoimmune hepatitis.

What evidence suggests that zetomipzomib might be an effective treatment for autoimmune hepatitis?

Research shows that zetomipzomib may help treat autoimmune hepatitis. In this trial, some participants will receive zetomipzomib with standard-of-care glucocorticoids, while others will receive a placebo with glucocorticoids. Studies have found that zetomipzomib can lead to more people experiencing complete remission, meaning their symptoms disappear, and it can also reduce the need for steroids. Initial trial results showed that patients had improvements in their disease activity markers, indicating less disease activity. Zetomipzomib targets a specific part of the immune system to help lower inflammation. These findings suggest that zetomipzomib could be a promising treatment option for those with autoimmune hepatitis. ^{1 2 3 5 6}

Who Is on the Research Team?

Ethan Weinberg, MD

Principal Investigator

University of Pennsylvania

Craig Lammert, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with autoimmune hepatitis (AIH) showing active disease or flare-ups despite ongoing treatment. Participants must have certain liver enzyme levels and a recent biopsy confirming AIH. They should be in early-stage liver impairment and willing to adjust their steroid therapy.

Inclusion Criteria

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

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, 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zetomipzomib or placebo weekly for 24 weeks in addition to standard-of-care treatment

24 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension

Eligible participants receive zetomipzomib for an additional 24 weeks

24 weeks

Weekly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Zetomipzomib

Trial Overview The study tests Zetomipzomib, an investigational drug, against a placebo alongside standard care for AIH patients for 24 weeks. There's also an optional extension where everyone can get Zetomipzomib for another 24 weeks.

How Is the Trial Designed?

Group I: zetomipzomib + standard-of-care (glucocorticoids) Experimental Treatment 1 Intervention

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

Group II: zetomipzomib + standard-of care (glucocorticoids) open-label extension period Experimental Treatment 1 Intervention

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.

Group III: placebo + standard-of-care (glucocorticoids) Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Kezar Life Sciences, Inc.

Lead Sponsor

Trials

7

Recruited

280+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05569759

NCT05569759 | A Study of Zetomipzomib (KZR-616) in ... This is a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis will receive zetomipzomib or placebo in addition to ...

2. ir.kezarlifesciences.com ir.kezarlifesciences.com/news-releases/news-release-details/kezar-life-sciences-announces-regulatory-update-zetomipzomib

Press Release Details Data generated from completed clinical trials provide evidence that zetomipzomib exhibits a favorable safety and tolerability profile for ...

3. hcplive.com hcplive.com/view/zetomipzomib-shows-promise-autoimmune-hepatitis-phase-2a-portola-trial

Zetomipzomib Shows Promise for Autoimmune Hepatitis in ... Results showed that, consistent with the AASLD treatment goals, zetomipzomib treatment resulted in greater rates of CR combined with reduction ...

4. firstwordpharma.com firstwordpharma.com/story/5944294

Kezar Life Sciences to Present Topline Results from the ... Zetomipzomib, a selective immunoproteasome inhibitor, is currently being evaluated in a Phase 2a clinical trial for autoimmune hepatitis. This ...

5. liverdiseasenews.com liverdiseasenews.com/news/zetomipzomib-induces-steroid-sparing-remission-autoimmune-hepatitis/

Zetomipzomib induces steroid-sparing remission in ... Top-line trial results showed that zetomipzomib induced biochemical disease remission while lowering steroid doses in autoimmune hepatitis.

6. ir.kezarlifesciences.com ir.kezarlifesciences.com/news-releases/news-release-details/kezar-life-sciences-announces-fda-has-lifted-partial-clinical

Press Release Details Data generated from completed clinical trials provide evidence that zetomipzomib exhibits a favorable safety and tolerability profile for ...