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A Study of Zetomipzomib (KZR-616) in Patients with Active Lupus Nephritis (PALIZADE)

Phase 2
Terminated
Conditions
Lupus Nephritis
Interventions
Drug: placebo
Registration Number
NCT05781750
Lead Sponsor
Kezar Life Sciences, Inc.
Brief Summary

The purpose of this study is to assess the efficacy and safety of zetomipzomib (30 mg or 60 mg) compared with placebo in achieving renal response after 52 weeks of treatment in patients with active lupus nephritis (LN).

Detailed Description

This study aims to investigate whether zetomipzomib, added to standard of care treatment in patients with active LN, is able to reduce disease activity over a treatment period of 52 weeks. The background standard of care therapy will be mycophenolate mofetil (MMF) and initial optional treatment with IV methylprednisolone, followed by a tapering course of oral corticosteroids.

Patients are required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis.

Patients will be randomized in a 2:1 ratio to receive either zetomipzomib (30 mg or 60 mg) or placebo administered as a subcutaneous injection once weekly for 52 weeks, followed by a 4-week safety follow-up period. Efficacy will be assessed by measuring the level of proteinuria (as measured by urine protein to creatinine ratio \[UPCR\]) and estimated glomerular filtration rate (eGFR) as compared to current standard of care treatment. Safety will also be assessed throughout the study to ensure an acceptable safety profile.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
84
Inclusion Criteria
  • Body mass index of ≥18 kg/m^2
  • eGFR ≥30 mL/min/1.73 m^2
  • Unequivocally positive ANA test result and/or a positive anti-dsDNA serum antibody test
  • Diagnosis of LN according to 2003 or 2018 ISN/RPS criteria and confirmed by renal biopsy performed within 12 months prior to Screening.
  • UPCR ≥1.0 (Class III/IV +/-V) or UPCR ≥2.0 (Class V)
  • Adequate hematologic, hepatic, and renal function

Key

Exclusion Criteria
  • Current or medical history of:

    • Central nervous system manifestations of SLE
    • Overlapping autoimmune condition that may affect study assessments/outcomes
    • Antiphospholipid syndrome with history of thromboembolic event of within the 52 weeks prior to Screening
    • Thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies (i.e., plasmapheresis or acute blood or platelet transfusions
    • Solid organ transplant or planned transplant during study
    • Malignancy of any type, with exceptions for non-melanoma skin cancers and certain cancers >5 years ago
  • Has received dialysis within the 52 weeks prior to Screening

  • Positive test at Screening for HIV, hepatitis B/C

  • Known intolerance to MMF or equivalent and corticosteroids

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
zetomipzomib 30 mg + standard-of-carezetomipzomibInitial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through 52 weeks of the treatment period.
zetomipzomib 60 mg + standard-of-carezetomipzomibInitial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through 52 weeks of the treatment period.
placebo + standard-of-careplaceboInitial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through 52 weeks of the treatment period.
Primary Outcome Measures
NameTimeMethod
To evaluate the efficacy of zetomipzomibBaseline through Week 37

Proportion of patients achieving complete renal response (CRR), defined as:

* A UPCR ≤0.5 in one 24-hour urine sample (for primary endpoint and Week 53) or 2 consecutive first morning void urine samples (for all other time points)

* An eGFR ≥60 mL/min/1.73 m\^2 or no confirmed decrease of \>20% from Baseline eGFR.

To evaluate safety of zetomipzomibBaseline through Week 56

Incidence and severity of adverse event (AE)s for each treatment group and patients treated with zetomipzomib compared with placebo

Secondary Outcome Measures
NameTimeMethod
Partial Renal Remission (PRR)Baseline through Week 25, Week 37, and Week 53

Proportion of patients achieving PRR, defined as:

* A ≥50% reduction of UPCR from Baseline, and to \<1.0 if the Baseline UPCR was \<3.0 or to \<3.0 if the Baseline value was ≥3.0.

CRRBaseline through Week 25 and Week 53

Proportion of patients achieving CRR

Trial Locations

Locations (182)

Nephrology Consultants, LLC

🇺🇸

Huntsville, Alabama, United States

Southwest Kidney Institute

🇺🇸

Surprise, Arizona, United States

Valerius Medical Group and Research Center of Greater Long Beach, Inc.

🇺🇸

Los Alamitos, California, United States

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center

🇺🇸

Torrance, California, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Reliant Medical Research

🇺🇸

Miami, Florida, United States

Phoenix Research Center, LLC

🇺🇸

Miami, Florida, United States

Elixia Central Florida

🇺🇸

Orlando, Florida, United States

West Broward Rheumatology Associates, Inc.

🇺🇸

Tamarac, Florida, United States

ClinCept Clinical Research

🇺🇸

Columbus, Georgia, United States

Scroll for more (172 remaining)
Nephrology Consultants, LLC
🇺🇸Huntsville, Alabama, United States

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