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

Phase 2TerminatedNCT05781750

Kezar Life Sciences, Inc.84 enrolled

Overview

The purpose of this study was 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).

This study aimed to investigate whether zetomipzomib, added to standard of care treatment in patients with active LN, was able to reduce disease activity over a treatment period of 52 weeks. The background standard of care therapy was mycophenolate mofetil (MMF) and initial optional treatment with IV methylprednisolone, followed by a tapering course of oral corticosteroids. Patients were required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis. Patients were 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 was to 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 was also assessed throughout the study to ensure an acceptable safety profile.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Lupus Nephritis

Interventions

zetomipzomibDRUG

Subcutaneous injection of zetomipzomib

placeboDRUG

Subcutaneous injection of placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key 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

Locations (50)

Outcomes

Primary Outcomes

Proportion of Patients Achieving Complete Renal Response

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.

Time frame: Week 37

Secondary Outcomes

Proportion of Patients Achieving Partial Renal Response (PRR)

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.

Time frame: Week 25 and Week 37

Proportion of Patients Achieving Complete Renal Response

Proportion of patients achieving complete renal response (CRR)

Time frame: Week 25

Change in UPCR

Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit

Time frame: Week 13, Week 25, and Week 37

Time to Complete Renal Response and Partial Renal Response

The comparison of the time to Complete Renal Response and Partial Renal Response for the zetomipzomib treatment groups (zetomipzomib 30mg and zetomipzomib 60mg) versus placebo. Hazard ratio (HR) and associated two-sided CIs are estimated using the Cox proportional hazards model. The model includes terms for treatment, the randomization stratification factors, and baseline UPCR (continuous).

Time frame: Baseline through Week 37

Proportion of Patients With UPCR ≤0.5

Proportion of patients with UPCR ≤0.5

Data from ClinicalTrials.gov

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