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

A Phase 2b, Randomized, Controlled Double-blind, Multicenter Study Comparing the Efficacy and Safety of Zetomipzomib (KZR-616) 30 mg or 60 mg With Placebo in Patients With Active Lupus Nephritis

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).

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: zetomipzomib; Drug: placebo

Detailed Description

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
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1902ADW
    • Framingham Medical Center
  • Buenos Aires, Argentina, C1015
    • Medical Research Organization
  • Buenos Aires, Argentina, C1406AGA
    • Aprillus Assistance and Research by Arcis Health
  • Buenos Aires, Argentina, C1426ABP
    • Dr. Doreski Medical Offices
  • Buenos Aires, Argentina, C1426BOS
    • Military Central Hospital
  • Pilar, Argentina, B1629ODT
    • Austral University Hospital
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, T4000
      • Mayo Clinic of UCMB SRL
• Brazil
  • São Paulo, Brazil, 05403-000
    • Clinical Hospital FMUSP
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Holy House of Mercy of Belo Horizonte
  • São Paulo
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Clinics Hospital FMRP
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Faculty of Medicine of SJRP
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangdong, China, 510280
      • Zhujiang Hospital of Southern Medical University
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
• Colombia
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080020
      • Costa Clinica
• Greece
  • Athens, Greece, 11527
    • Laiko General Hospital of Athens
• Guatemala
  • Guatemala City, Guatemala, 01010
    • Medical Clinic Specialized in Internal Medicine and Rheumatology
  • Guatemala City, Guatemala, 01011
    • Medical Clinic Specialized in Internal Medicine and Rheumatology
  • Guatemala City, Guatemala, 01009
    • Center for Advanced Health Clinical Studies
  • Guatemala City, Guatemala, 01010
    • Clinical Research Center, S.A.
• India
  • Chhattisgarh
    • Raipur, Chhattisgarh, India, 492099
      • All India Institute of Medical Sciences
  • Guajrat
    • Surat, Guajrat, India, 395002
      • Nirmal Hospital
    • Surat, Guajrat, India, 395010
      • Unity Hospital
  • Gujarat
    • Ahmedabad, Gujarat, India, 380005
      • Panchshil Hospital
  • Kerala
    • Thrissur, Kerala, India, 680007
      • Elite Mission Hospital
  • Maharashtra
    • Aurangabad, Maharashtra, India, 431003
      • MGM Medical College and Hospital
    • Nagpur, Maharashtra, India, 440001
      • Kingsway Hospital
    • Nagpur, Maharashtra, India, 440012
      • Jasleen Hospital
    • Nashik, Maharashtra, India, 422101
      • Assured Care Plus Hospital
  • NCT of Delhi
    • New Delhi, NCT of Delhi, India, 110060
      • Sir Ganga Ram Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302001
      • SMS Medical College
  • Telangana
    • Hyderabad, Telangana, India, India
      • Yashoda Hospitals
    • Secunderabad, Telangana, India, 500003
      • Krishna Institute of Medical Science
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Kuala Lumpur
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 50450
      • Prince Court Medical Centre
  • Perak
    • Ipoh, Perak, Malaysia, 30450
      • Hospital Raja Permaisuri Bainun
  • Selangor
    • Batu Caves, Selangor, Malaysia, 68100
      • Hospital Selayang
    • Kajang, Selangor, Malaysia, 43000
      • Hospital Sultan Idris Shah Serdang
• Philippines
  • Manila, Philippines, 1015
    • University of Santo Tomas Hospital
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Mary Mediatrix Medical Center
  • Iloilo
    • Iloilo City, Iloilo, Philippines, 5000
      • Iloilo Doctors' Hospital
  • National Capital Region
    • Manila, National Capital Region, Philippines, 1000
      • ManilaMed - Medical Center Manila
    • Quezon City, National Capital Region, Philippines, 1118
      • Far Eastern University Hospital Nicanor Reyes Medical Foundation
    • Quezon City, National Capital Region, Philippines, 1102
      • St. Luke's Medical Center
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Phoenix Pharma
• South Korea
  • Seoul, South Korea, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• United States
  • Louisiana
    • Lake Charles, Louisiana, United States, 70605
      • Accurate Clinical Research - Lake Charles
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Nephrology Associates, Inc
  • Texas
    • Colleyville, Texas, United States, 76034
      • Precision Comprehensive Clinical Research Solutions
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center (PCRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zetomipzomib 30 mg + standard-of-care; Participants randomized to be treated with initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through the treatment period in addition to background standard of care therapy.	Drug: zetomipzomib; Subcutaneous injection of zetomipzomib; Other Names: KZR-616
Experimental: zetomipzomib 60 mg + standard-of-care; Participants randomized to be treated with initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through the treatment period in addition to background standard of care therapy.	Drug: zetomipzomib; Subcutaneous injection of zetomipzomib; Other Names: KZR-616
Placebo Comparator: placebo + standard-of-care; Participants randomized to be treated with initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through the treatment period in addition to background standard of care therapy.	Drug: placebo; Subcutaneous injection of placebo; Other Names: matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 37

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 25 and Week 37
Proportion of Patients Achieving Complete Renal Response	Proportion of patients achieving complete renal response (CRR)	Week 25
Change in UPCR	Percentage change from Baseline in Urine Protein to Creatinine Ratio (UPCR) by visit	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).	Baseline through Week 37
Proportion of Patients With UPCR ≤0.5	Proportion of patients with UPCR ≤0.5	Week 13, Week 25, and Week 37
Percent Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K)	Percent change from Baseline in clinical SLEDAI-2K score. The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity.	Week 13, Week 25, and Week 37

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in UPCR	Percentage change from Baseline in UPCR by visit	Baseline through Week 53
Time to event	Time to CRR, PRR, death or renal events	Baseline through Week 53
CRR and successful prednisone taper	Proportion of patients achieving CRR with successful taper of prednisone or equivalent by Week 17	Baseline through Week 25, Week 37, and Week 53
CRR and no prednisone use	Proportion of patients achieving CRR with no use of prednisone or equivalent during the 8 weeks prior to renal response assessment	Baseline through Week 25, Week 37, and Week 53
UPCR ≤0.5	Proportion of patients with UPCR ≤0.5	Baseline through Week 13, Week 25, Week 37, and Week 53
CRR with UPCR ≤ ULN	Proportion of patients achieving CRR with UPCR ≤ Upper Limit of Normal	Baseline through Week 25, Week 37, and Week 53
Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K)	Changes from Baseline in clinical SLEDAI-2K score. The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity.	Baseline through Week 56
Change in Patient-reported Outcomes	Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) assessment. The EQ-5D-5L descriptive system comprises five dimensions (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression), each with five response levels (no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). A higher score in each category indicates a higher level of patient-reported dysfunction or discomfort.	Baseline through Week 56

Collaborators and Investigators

• Sponsor: Kezar Life Sciences, Inc.
• Investigators: Study Director: Kezar, Kezar Life Sciences, Inc.

Publications and helpful links

Helpful Links

• Corporate website

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2023
• Primary Completion (Actual): November 8, 2024
• Study Completion (Actual): November 8, 2024

Study Registration Dates

• First Submitted: March 12, 2023
• First Submitted That Met QC Criteria: March 12, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: steroids; glucocorticoids; complete renal response; immunoproteasome inhibition; selective immunoproteasome inhibition; partial renal response; UPCR (urine protein to creatinine ratio); eGFR (estimated glomerular filtration rate); SLE (systemic lupus erythematosus)
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; KZR-616
• Other Study ID Numbers: KZR-616-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No