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

Lupus Nephritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05781750
• Other study ID #: KZR-616-202
• Status: Recruiting
• Phase: Phase 2
• Start date: November 3, 2023
• Est. completion date: July 2026

Study information

• Verified date: May 2024
• Source: Kezar Life Sciences, Inc.
• Contact: Kezar Life Sciences, Inc
• Phone: (650) 640-4480
• Email: PALIZADE[@]kezarbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 279
• Est. completion date: July 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• zetomipzomib
Subcutaneous injection of zetomipzomib
• placebo
Subcutaneous injection of placebo

Locations

Country	Name	City	State
Argentina	Aprillus Assistance and Research by Arcis Health	Buenos Aires
Argentina	Dr. Doreski Medical Offices	Buenos Aires
Argentina	Framingham Medical Center	Buenos Aires
Argentina	Medical Research Organization	Buenos Aires
Argentina	Military Central Hospital	Buenos Aires
Argentina	Austral University Hospital	Pilar
Argentina	The Medical Institute of the Clinical Studies Foundation	Rosario	Santa Fe
Argentina	Mayo Clinic of UCMB SRL	San Miguel De Tucumán	Tucumán
Australia	Monash Health	Clayton	Victoria
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	St George Hospital	Kogarah	New South Wales
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Gold Coast Hospital and Health Service	Southport	Queensland
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Wollongong Hospital	Wollongong	New South Wales
Brazil	Holy House of Mercy of Belo Horizonte	Belo Horizonte	Minas Gerais
Brazil	Brasília Hospital	Brasília	Federal District
Brazil	L2IP - Clinical Research Institute	Brasília	Distrito Federal
Brazil	Pro-Renal Institute Brazil	Curitiba	Paraná
Brazil	Pro-Rim Foundation Research Center	Joinville	Santa Catarina
Brazil	Hospital Association Clinical Research Center - Windmills Hospital	Porto Alegre	Rio Grande Do Sul
Brazil	LMK Medical Services SS	Porto Alegre	Rio Grande Do Sol
Brazil	Clinics Hospital FMRP	Ribeirão Preto	São Paulo
Brazil	Hospital São Lucas Copacabana	Rio De Janeiro
Brazil	Senhor de Bonfim Clinic	Salvador	Bahia
Brazil	Specialized Rheumatology Services of Bahia	Salvador	Bahia
Brazil	Praxis Medical Research	Santo André	São Paulo
Brazil	Multidisciplinary Center for Clinical Studies	São Bernardo Do Campo	São Paulo
Brazil	Faculty of Medicine of SJRP	São José Do Rio Preto	São Paulo
Brazil	Hospital São Domingos	São Luís	Maranhão
Brazil	Clinical Hospital FMUSP	São Paulo
Brazil	Hospital Nove de Julho	São Paulo
Brazil	Oswaldo Ramos Foundation	São Paulo
Brazil	Saint Marcelina Hospital	São Paulo
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
Colombia	Costa Clinica	Barranquilla	Atlántico
Colombia	Cardiovascular Foundation of Colombia	Bucaramanga	Santander
Colombia	Healthy Medical Center S.A.S.	Zipaquirá	Cundinamarca
Croatia	University Hospital of Split	Split
Croatia	Solmed Clinic	Zagreb
Croatia	University Hospital Center Zagreb	Zagreb
Greece	Laiko General Hospital of Athens	Athens
Greece	Laiko General Hospital of Athens	Athens
Greece	University General Hospital of Larisa	Larisa
Greece	Ippokratio General Hospital of Thessaloniki	Thessaloniki
Guatemala	Center for Advanced Health Clinical Studies	Guatemala
Guatemala	Clinical Research Center, S.A.	Guatemala
Guatemala	Medical Clinic Specialized in Nephrology	Guatemala
Guatemala	Medical Clinic Specialized in Internal Medicine and Rheumatology	Guatemala City
Guatemala	Medical Clinic Specialized in Internal Medicine and Rheumatology	Guatemala City
India	Panchshil Hospital	Ahmedabad	Gujarat
India	MGM Medical College and Hospital	Aurangabad	Maharashtra
India	KLES Dr Prabhakar Kore Hospital and Medical Research Centre	Belgaum	Karnataka
India	Yashoda Hospitals	Hyderabad	Telangana
India	SMS Medical College	Jaipur	Rajasthan
India	Fortis Hospital	Kolkata	West Bengal
India	Jasleen Hospital	Nagpur	Maharashtra
India	Kingsway Hospital	Nagpur	Maharashtra
India	Assured Care Plus Hospital	Nashik	Maharashtra
India	Sir Ganga Ram Hospital	New Delhi	NCT Of Delhi
India	All India Institute of Medical Sciences	Raipur	Chhattisgarh
India	Krishna Institute of Medical Science	Secunderabad	Telangana
India	Nirmal Hospital	Surat	Guajrat
India	Unity Hospital	Surat	Guajrat
India	Elite Mission Hospital	Thrissur	Kerala
Korea, Republic of	CHA Bundang Medical Center, CHA University	Gyeonggi-do
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Soon Chun Hyang University Hospital Seoul	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Malaysia	Hospital Selayang	Batu Caves	Selangor
Malaysia	Hospital Raja Permaisuri Bainun	Ipoh	Perak
Malaysia	Hospital Sultan Idris Shah Serdang	Kajang	Selangor
Malaysia	Hospital Canselor Tuanku Muhriz UKM	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Prince Court Medical Centre	Kuala Lumpur	Wilayah Persekutuan
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Al Sultan Abdullah	Kuala Selangor
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan	Pahang
Philippines	Iloilo Doctors' Hospital	Iloilo City	Iloilo
Philippines	Mary Mediatrix Medical Center	Lipa City	Batangas
Philippines	University of Santo Tomas Hospital	Manila
Philippines	Chinese General Hospital	Manila City	National Capital Region
Philippines	ManilaMed - Medical Center Manila	Manila City	National Capital Region
Philippines	Far Eastern University Hospital Nicanor Reyes Medical Foundation	Quezon City	National Capital Region
Philippines	St. Luke's Medical Center	Quezon City	National Capital Region
Philippines	St. Luke's Medical Center	Quezon City	National Capital Region
Portugal	Braga Academic Clinical Center - Braga Hospital	Braga
Portugal	Western Lisbon Hospital Center, EPE - Santa Cruz Hospital	Carnaxide
Portugal	Lady of Oliveira Hospital - Guimarães, EPE	Guimarães
Portugal	Lisbon North Hospital and University Center (CHULN), E.P.E - Santa Maria Hospital	Lisboa
Portugal	Saint Anthony University Hospital Center	Porto
Portugal	Setúbal Hospital Center EPE	Setúbal
Puerto Rico	GCM Medical Group	San Juan
Singapore	National University Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
South Africa	Arthritis Clinical Trial Centre	Cape Town	Western Cape
South Africa	CRISMO Research Centre	Germiston	Gauteng
South Africa	Phoenix Pharma	Port Elizabeth	Eastern Cape
Spain	Clinical Hospital of Barcelona	Barcelona
Spain	Puigvert Foundation	Barcelona
Spain	Bellvitge University Hospital	L'Hospitalet De Llobregat	Barcelona
Spain	University Hospital Arnau de Vilanova	Lleida
Spain	Gregorio Marañón General University Hospital	Madrid
Spain	San Carlos Clinical Hospital	Madrid
Spain	University Hospital October 12	Madrid
Spain	University of Navarra Hospital	Pamplona	Navarra
Spain	Virgen del Rocío University Hospital	Sevilla
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital	Keelung
Taiwan	Far Eastern Memorial Hospital	New Taipei
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
United Kingdom	Royal Derby Hospitals, University Hospitals of Derby and Burton	Derby	Derbyshire
United Kingdom	Churchill Hospital	Headington	Oxford
United Kingdom	Leicester General Hospital	Leicester
United Kingdom	Hammersmith Hospital	London
United Kingdom	St. Georges University Hospitals	London
United Kingdom	Salford Royal NHS Foundation Trust	Salford	Greater Manchester
United Kingdom	Sunderland Royal Hospital	Sunderland	Tyne And Wear
United States	Northwestern University	Chicago	Illinois
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	ClinCept Clinical Research	Columbus	Georgia
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Texas Kidney Institute	Dallas	Texas
United States	Southeast Kidney Associates	East Point	Georgia
United States	Nephrology Associates, Inc	East Providence	Rhode Island
United States	Northwell Health	Great Neck	New York
United States	Prolato Clinical Research Center (PCRC)	Houston	Texas
United States	Nephrology Consultants, LLC	Huntsville	Alabama
United States	Accurate Clinical Research - Lake Charles	Lake Charles	Louisiana
United States	Clinical Renal Associates	Langhorne	Pennsylvania
United States	North Texas Kidney Disease Associates	Lewisville	Texas
United States	Valerius Medical Group and Research Center of Greater Long Beach, Inc.	Los Alamitos	California
United States	Phoenix Research Center, LLC	Miami	Florida
United States	Reliant Medical Research	Miami	Florida
United States	NYU Langone Health	New York	New York
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Elixia Central Florida	Orlando	Florida
United States	Renal Specialists of Houston	Pasadena	Texas
United States	Hypertension and Nephrology Inc	Providence	Rhode Island
United States	Southwest Kidney Institute	Surprise	Arizona
United States	West Broward Rheumatology Associates, Inc.	Tamarac	Florida
United States	The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Clinical Renal Associates, Ltd.	Upland	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Kezar Life Sciences, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  China,  Colombia,  Croatia,  Greece,  Guatemala,  India,  Korea, Republic of,  Malaysia,  Philippines,  Portugal,  Puerto Rico,  Singapore,  South Africa,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in UPCR	Percentage change from Baseline in UPCR by visit	Baseline through Week 53
Other	Time to event	Time to CRR, PRR, death or renal events	Baseline through Week 53
Other	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
Other	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
Other	UPCR =0.5	Proportion of patients with UPCR =0.5	Baseline through Week 13, Week 25, Week 37, and Week 53
Other	CRR with UPCR = ULN	Proportion of patients achieving CRR with UPCR = Upper Limit of Normal	Baseline through Week 25, Week 37, and Week 53
Other	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
Other	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
Primary	To evaluate the efficacy of zetomipzomib	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.	Baseline through Week 37
Primary	To evaluate safety of zetomipzomib	Incidence and severity of adverse event (AE)s for each treatment group and patients treated with zetomipzomib compared with placebo	Baseline through Week 56
Secondary	Partial Renal Remission (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.	Baseline through Week 25, Week 37, and Week 53
Secondary	CRR	Proportion of patients achieving CRR	Baseline through Week 25 and Week 53

External Links

•   Corporate website