Clinical trial NCT05781750: A Study of Zetomipzomib (KZR-616) in Patients with Active Lupus Nephritis (PALIZADE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lupus Nephritis
Keywords: immunoproteasome inhibition
selective immunoproteasome inhibition
complete renal response
partial renal response
glucocorticoids
steroids
SLE (systemic lupus erythematosus
UPCR (urine protein to creatinine ratio)
eGFR (estimated glomerular filtration rate)
Lead sponsor: Kezar Life Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-23
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the efficacy of zetomipzomib
timeFrame: Baseline through Week 37
measure: To evaluate safety of zetomipzomib
timeFrame: Baseline through Week 56
Secondary outcomes:
measure: Partial Renal Remission (PRR)
timeFrame: Baseline through Week 25, Week 37, and Week 53
measure: CRR
timeFrame: Baseline through Week 25 and Week 53
Other outcomes:
measure: Change in UPCR
timeFrame: Baseline through Week 53
measure: Time to event
timeFrame: Baseline through Week 53
measure: CRR and successful prednisone taper
timeFrame: Baseline through Week 25, Week 37, and Week 53
measure: CRR and no prednisone use
timeFrame: Baseline through Week 25, Week 37, and Week 53
measure: UPCR ≤0.5
timeFrame: Baseline through Week 13, Week 25, Week 37, and Week 53
measure: CRR with UPCR ≤ ULN
timeFrame: Baseline through Week 25, Week 37, and Week 53
measure: Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K)
timeFrame: Baseline through Week 56
measure: Change in Patient-reported Outcomes
timeFrame: Baseline through Week 56
Locations:
city: Huntsville
country: United States
facility: Nephrology Consultants, LLC
state: Alabama
city: Surprise
country: United States
facility: Southwest Kidney Institute
state: Arizona
city: Los Alamitos
country: United States
facility: Valerius Medical Group and Research Center of Greater Long Beach, Inc.
state: California
city: Torrance
country: United States
facility: The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Reliant Medical Research
state: Florida
city: Miami
country: United States
facility: Phoenix Research Center, LLC
state: Florida
city: Orlando
country: United States
facility: Elixia Central Florida
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates, Inc.
state: Florida
city: Columbus
country: United States
facility: ClinCept Clinical Research
state: Georgia
city: East Point
country: United States
facility: Southeast Kidney Associates
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Lake Charles
country: United States
facility: Accurate Clinical Research - Lake Charles
state: Louisiana
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Langhorne
country: United States
facility: Clinical Renal Associates
state: Pennsylvania
city: Upland
country: United States
facility: Clinical Renal Associates, Ltd.
state: Pennsylvania
city: East Providence
country: United States
facility: Nephrology Associates, Inc
state: Rhode Island
city: Providence
country: United States
facility: Hypertension and Nephrology Inc
state: Rhode Island
city: Amarillo
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: Colleyville
country: United States
facility: Precision Comprehensive Clinical Research Solutions
state: Texas
city: Dallas
country: United States
facility: Texas Kidney Institute
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center (PCRC)
state: Texas
city: Lewisville
country: United States
facility: North Texas Kidney Disease Associates
state: Texas
city: Pasadena
country: United States
facility: Renal Specialists of Houston
state: Texas
city: Rosario
country: Argentina
facility: The Medical Institute of the Clinical Studies Foundation
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: Mayo Clinic of UCMB SRL
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Framingham Medical Center
city: Buenos Aires
country: Argentina
facility: Medical Research Organization
city: Buenos Aires
country: Argentina
facility: Aprillus Assistance and Research by Arcis Health
city: Buenos Aires
country: Argentina
facility: Dr. Doreski Medical Offices
city: Buenos Aires
country: Argentina
facility: Military Central Hospital
city: Pilar
country: Argentina
facility: Austral University Hospital
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast Hospital and Health Service
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Salvador
country: Brazil
facility: Specialized Rheumatology Services of Bahia
state: Bahia
city: Salvador
country: Brazil
facility: Senhor de Bonfim Clinic
state: Bahia
city: Brasília
country: Brazil
facility: L2IP - Clinical Research Institute
state: Distrito Federal
city: Brasília
country: Brazil
facility: Brasília Hospital
state: Federal District
city: São Luís
country: Brazil
facility: Hospital São Domingos
state: Maranhão
city: Belo Horizonte
country: Brazil
facility: Holy House of Mercy of Belo Horizonte
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Pro-Renal Institute Brazil
state: Paraná
city: Porto Alegre
country: Brazil
facility: LMK Medical Services SS
state: Rio Grande do Sol
city: Porto Alegre
country: Brazil
facility: Hospital Association Clinical Research Center - Windmills Hospital
state: Rio Grande do Sul
city: Joinville
country: Brazil
facility: Pro-Rim Foundation Research Center
state: Santa Catarina
city: Ribeirão Preto
country: Brazil
facility: Clinics Hospital FMRP
state: São Paulo
city: Santo André
country: Brazil
facility: Praxis Medical Research
state: São Paulo
city: São Bernardo Do Campo
country: Brazil
facility: Multidisciplinary Center for Clinical Studies
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Faculty of Medicine of SJRP
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Hospital São Lucas Copacabana
city: São Paulo
country: Brazil
facility: Hospital Nove de Julho
city: São Paulo
country: Brazil
facility: Oswaldo Ramos Foundation
city: São Paulo
country: Brazil
facility: Clinical Hospital FMUSP
city: São Paulo
country: Brazil
facility: Saint Marcelina Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Xiamen
country: China
facility: The Fifth Hospital of Xiamen
state: Fujian
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan Hospital of Traditional Chinese Medicine
state: Guangdong
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Huangpu
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
state: Shanxi
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
state: Sichuan
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Medellín
country: Colombia
facility: Alma Mater Hospital of Antioquia
state: Antioquia
city: Barranquilla
country: Colombia
facility: Costa Clinica
state: Atlántico
city: Zipaquirá
country: Colombia
facility: Healthy Medical Center S.A.S.
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Cardiovascular Foundation of Colombia
state: Santander
city: Cali
country: Colombia
facility: IPS Julian Coronel Medical Center SAS
state: Valle de Cauca
city: Split
country: Croatia
facility: University Hospital of Split
city: Zagreb
country: Croatia
facility: Solmed Clinic
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Larisa
country: Greece
facility: University General Hospital of Larisa
city: Thessaloniki
country: Greece
facility: Ippokratio General Hospital of Thessaloniki
city: Guatemala City
country: Guatemala
facility: Medical Clinic Specialized in Internal Medicine and Rheumatology
city: Guatemala City
country: Guatemala
facility: Medical Clinic Specialized in Internal Medicine and Rheumatology
city: Guatemala
country: Guatemala
facility: Center for Advanced Health Clinical Studies
city: Guatemala
country: Guatemala
facility: Clinical Research Center, S.A.
city: Guatemala
country: Guatemala
facility: Medical Clinic Specialized in Nephrology
city: Raipur
country: India
facility: All India Institute of Medical Sciences
state: Chhattisgarh
city: Surat
country: India
facility: Nirmal Hospital
state: Guajrat
city: Surat
country: India
facility: Unity Hospital
state: Guajrat
city: Ahmedabad
country: India
facility: Panchshil Hospital
state: Gujarat
city: Belgaum
country: India
facility: KLES Dr Prabhakar Kore Hospital and Medical Research Centre
state: Karnataka
city: Thrissur
country: India
facility: Elite Mission Hospital
state: Kerala
city: Aurangabad
country: India
facility: MGM Medical College and Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Kingsway Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Jasleen Hospital
state: Maharashtra
city: Nashik
country: India
facility: Assured Care Plus Hospital
state: Maharashtra
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: NCT of Delhi
city: Jaipur
country: India
facility: SMS Medical College
state: Rajasthan
city: Ranipet
country: India
facility: Christian Medical College
state: Tamil Nadu
city: Hyderabad
country: India
facility: Yashoda Hospitals
state: Telangana
city: Secunderabad
country: India
facility: Krishna Institute of Medical Science
state: Telangana
city: Kolkata
country: India
facility: Institute of Post Graduate Medical Education and Research / SSKM Hospital
state: West Bengal
city: Kolkata
country: India
facility: Fortis Hospital
state: West Bengal
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
state: Selangor
city: Kajang
country: Malaysia
facility: Hospital Sultan Idris Shah Serdang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Prince Court Medical Centre
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Hospital Canselor Tuanku Muhriz UKM
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuala Selangor
country: Malaysia
facility: Hospital Al Sultan Abdullah
city: Arequipa
country: Peru
facility: Internal Medicine and Critical Disease Research Unit
city: Lima
country: Peru
facility: Institute of Gynecology and Reproduction
city: Lima
country: Peru
facility: San Juan Bautista Clinic
city: Lipa City
country: Philippines
facility: Mary Mediatrix Medical Center
state: Batangas
city: Iloilo City
country: Philippines
facility: Iloilo Doctors' Hospital
state: Iloilo
city: Manila City
country: Philippines
facility: ManilaMed - Medical Center Manila
state: National Capital Region
city: Manila City
country: Philippines
facility: Chinese General Hospital
state: National Capital Region
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
state: National Capital Region
city: Quezon City
country: Philippines
facility: Far Eastern University Hospital Nicanor Reyes Medical Foundation
state: National Capital Region
city: Manila
country: Philippines
facility: University of Santo Tomas Hospital
city: Braga
country: Portugal
facility: Braga Academic Clinical Center - Braga Hospital
city: Carnaxide
country: Portugal
facility: Western Lisbon Hospital Center, EPE - Santa Cruz Hospital
city: Guimarães
country: Portugal
facility: Lady of Oliveira Hospital - Guimarães, EPE
city: Lisboa
country: Portugal
facility: Lisbon North Hospital and University Center (CHULN), E.P.E - Santa Maria Hospital
city: Porto
country: Portugal
facility: Saint Anthony University Hospital Center
city: Setúbal
country: Portugal
facility: Setúbal Hospital Center EPE
city: San Juan
country: Puerto Rico
facility: GCM Medical Group
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Krusevac
country: Serbia
facility: General Hospital Krusevac
city: Niš
country: Serbia
facility: University Clinical Center Niš
city: Port Elizabeth
country: South Africa
facility: Phoenix Pharma
state: Eastern Cape
city: Germiston
country: South Africa
facility: CRISMO Research Centre
state: Gauteng
city: Cape Town
country: South Africa
facility: Arthritis Clinical Trial Centre
state: Western Cape
city: L'Hospitalet De Llobregat
country: Spain
facility: Bellvitge University Hospital
state: Barcelona
city: Pamplona
country: Spain
facility: University of Navarra Hospital
state: Navarra
city: Barcelona
country: Spain
facility: Puigvert Foundation
city: Barcelona
country: Spain
facility: Clinical Hospital of Barcelona
city: Lleida
country: Spain
facility: University Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Gregorio Marañón General University Hospital
city: Madrid
country: Spain
facility: San Carlos Clinical Hospital
city: Madrid
country: Spain
facility: University Hospital October 12
city: Sevilla
country: Spain
facility: Virgen del Rocío University Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: New Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Derby
country: United Kingdom
facility: Royal Derby Hospitals, University Hospitals of Derby and Burton
state: Derbyshire
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
state: Greater Manchester
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxford
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: Tyne and Wear
city: London
country: United Kingdom
facility: King's College Hospital
state: UK
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: St. Georges University Hospitals
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: West Broward Rheumatology Associates, Inc.
name: Steven Kimmel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Kidney Institute
name: Sumit Kumar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Phoenix Research Center, LLC
name: Amarilis Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nephrology Consultants, LLC
name: David Tietjen, MD
role: PRINCIPAL_INVESTIGATOR
References: