Back to resultsA Study of Zetomipzomib (KZR-616) in Patients With Active Lupus Nephritis (PALIZADE)
Primary Purpose
Lupus Nephritis
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
zetomipzomib
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Nephritis focused on measuring 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)
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
Sites / Locations
- Nephrology Consultants, LLCRecruiting
- Valerius Medical Group and Research Center of Greater Long Beach, Inc.Recruiting
- The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical CenterRecruiting
- Reliant Medical ResearchRecruiting
- Phoenix Research Center, LLCRecruiting
- West Broward Rheumatology Associates, Inc.Recruiting
- ClinCept Clinical ResearchRecruiting
- Accurate Clinical Research - Lake CharlesRecruiting
- Precision Comprehensive Clinical Research SolutionsRecruiting
- Texas Kidney InstituteRecruiting
- Prolato Clinical Research Center (PCRC)Recruiting
- Mayo Clinic of UCMB SRLRecruiting
- St George HospitalRecruiting
- Medical Clinic Specialized in Internal Medicine and RheumatologyRecruiting
- Medical Clinic Specialized in Internal Medicine and RheumatologyRecruiting
- GCM Medical GroupRecruiting
- National University HospitalRecruiting
- Tan Tock Seng HospitalRecruiting
- Phoenix PharmaRecruiting
- CRISMO Research CentreRecruiting
- Arthritis Clinical Trial CentreRecruiting
- China Medical University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
zetomipzomib 30 mg + standard-of-care
zetomipzomib 60 mg + standard-of-care
placebo + standard-of-care
Arm Description
Initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through 52 weeks of the treatment period.
Initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through 52 weeks of the treatment period.
Initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through 52 weeks of the treatment period.
Outcomes
Primary Outcome Measures
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.
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
Secondary Outcome Measures
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.
CRR
Proportion of patients achieving CRR
Full Information
NCT ID
NCT05781750
First Posted
March 12, 2023
Last Updated
October 20, 2023
Sponsor
Kezar Life Sciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05781750
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 26, 2023 (Actual)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kezar Life Sciences, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
279 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
zetomipzomib 30 mg + standard-of-care
Arm Type
Experimental
Arm Description
Initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through 52 weeks of the treatment period.
Arm Title
zetomipzomib 60 mg + standard-of-care
Arm Type
Experimental
Arm Description
Initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through 52 weeks of the treatment period.
Arm Title
placebo + standard-of-care
Arm Type
Placebo Comparator
Arm Description
Initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through 52 weeks of the treatment period.
Intervention Type
Drug
Intervention Name(s)
zetomipzomib
Other Intervention Name(s)
KZR-616
Intervention Description
Subcutaneous injection of zetomipzomib
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
matching placebo
Intervention Description
Subcutaneous injection of placebo
Primary Outcome Measure Information:
Title
To evaluate the efficacy of zetomipzomib
Description
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
Baseline through Week 37
Title
To evaluate safety of zetomipzomib
Description
Incidence and severity of adverse event (AE)s for each treatment group and patients treated with zetomipzomib compared with placebo
Time Frame
Baseline through Week 56
Secondary Outcome Measure Information:
Title
Partial Renal Remission (PRR)
Description
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
Baseline through Week 25, Week 37, and Week 53
Title
CRR
Description
Proportion of patients achieving CRR
Time Frame
Baseline through Week 25 and Week 53
Other Pre-specified Outcome Measures:
Title
Change in UPCR
Description
Percentage change from Baseline in UPCR by visit
Time Frame
Baseline through Week 53
Title
Time to event
Description
Time to CRR, PRR, death or renal events
Time Frame
Baseline through Week 53
Title
CRR and successful prednisone taper
Description
Proportion of patients achieving CRR with successful taper of prednisone or equivalent by Week 17
Time Frame
Baseline through Week 25, Week 37, and Week 53
Title
CRR and no prednisone use
Description
Proportion of patients achieving CRR with no use of prednisone or equivalent during the 8 weeks prior to renal response assessment
Time Frame
Baseline through Week 25, Week 37, and Week 53
Title
UPCR ≤0.5
Description
Proportion of patients with UPCR ≤0.5
Time Frame
Baseline through Week 13, Week 25, Week 37, and Week 53
Title
CRR with UPCR ≤ ULN
Description
Proportion of patients achieving CRR with UPCR ≤ Upper Limit of Normal
Time Frame
Baseline through Week 25, Week 37, and Week 53
Title
Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K)
Description
Changes from Baseline in clinical SLEDAI-2K score. The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity.
Time Frame
Baseline through Week 56
Title
Change in Patient-reported Outcomes
Description
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.
Time Frame
Baseline through Week 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kezar Life Sciences, Inc
Phone
(650) 640-4480
Email
PALIZADE@kezarbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Kimmel, MD
Organizational Affiliation
West Broward Rheumatology Associates, Inc.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sumit Kumar, MD
Organizational Affiliation
Texas Kidney Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Amarilis Gonzalez, MD
Organizational Affiliation
Phoenix Research Center, LLC
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Tietjen, MD
Organizational Affiliation
Nephrology Consultants, LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nephrology Consultants, LLC
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Tietjen, MD
First Name & Middle Initial & Last Name & Degree
David Tietjen, MD
Facility Name
Valerius Medical Group and Research Center of Greater Long Beach, Inc.
City
Los Alamitos
State/Province
California
ZIP/Postal Code
90720
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathaniel Neal, MD
First Name & Middle Initial & Last Name & Degree
Nathaniel Neal, MD
Facility Name
The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
George Karpouzas, MD
First Name & Middle Initial & Last Name & Degree
George Karpouzas, MD
Facility Name
Reliant Medical Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramses Vega, MD
First Name & Middle Initial & Last Name & Degree
Ramses Vega, MD
Facility Name
Phoenix Research Center, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33186
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amarilis Gonzalez, MD
First Name & Middle Initial & Last Name & Degree
Amarilis Gonzalez, MD
Facility Name
West Broward Rheumatology Associates, Inc.
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Kimmel, MD
First Name & Middle Initial & Last Name & Degree
Steven Kimmel, MD
Facility Name
ClinCept Clinical Research
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fahd Syed, MD
First Name & Middle Initial & Last Name & Degree
Fahd Syed, MD
Facility Name
Accurate Clinical Research - Lake Charles
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70605
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enrique Mendez, MD
First Name & Middle Initial & Last Name & Degree
Enrique Mendez, MD
Facility Name
Precision Comprehensive Clinical Research Solutions
City
Colleyville
State/Province
Texas
ZIP/Postal Code
76034
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dhiman Basu, MD
First Name & Middle Initial & Last Name & Degree
Dhiman Basu, MD
Facility Name
Texas Kidney Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sumit Kumar, MD
First Name & Middle Initial & Last Name & Degree
Sumit Kumar, MD
Facility Name
Prolato Clinical Research Center (PCRC)
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Biruh Workeneh, MD
First Name & Middle Initial & Last Name & Degree
Biruh Workeneh, MD
Facility Name
Mayo Clinic of UCMB SRL
City
San Miguel De Tucumán
State/Province
Tucumán
ZIP/Postal Code
T4000
Country
Argentina
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Francisco Colombres
First Name & Middle Initial & Last Name & Degree
Dr. Francisco Colombres
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Sunil Badve
First Name & Middle Initial & Last Name & Degree
Dr. Sunil Badve
Facility Name
Medical Clinic Specialized in Internal Medicine and Rheumatology
City
Guatemala City
ZIP/Postal Code
01010
Country
Guatemala
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Nilmo Chávez
First Name & Middle Initial & Last Name & Degree
Dr. Nilmo Chávez
Facility Name
Medical Clinic Specialized in Internal Medicine and Rheumatology
City
Guatemala City
ZIP/Postal Code
01011
Country
Guatemala
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Maynor Herrera
First Name & Middle Initial & Last Name & Degree
Dr. Maynor Herrera
Facility Name
GCM Medical Group
City
San Juan
ZIP/Postal Code
00917
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karina Vila-Rivera, MD
First Name & Middle Initial & Last Name & Degree
Karina Vila-Rivera, MD
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Boon Wee Teo
First Name & Middle Initial & Last Name & Degree
Dr. Boon Wee Teo
Facility Name
Tan Tock Seng Hospital
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. See Cheng Yeo
First Name & Middle Initial & Last Name & Degree
Dr. See Cheng Yeo
Facility Name
Phoenix Pharma
City
Port Elizabeth
State/Province
Eastern Cape
ZIP/Postal Code
6001
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Daniel Malan
First Name & Middle Initial & Last Name & Degree
Dr. Daniel Malan
Facility Name
CRISMO Research Centre
City
Germiston
State/Province
Gauteng
ZIP/Postal Code
1401
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Wesley Tulleken
First Name & Middle Initial & Last Name & Degree
Dr. Wesley Tulleken
Facility Name
Arthritis Clinical Trial Centre
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7405
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Rehana Bhorat
First Name & Middle Initial & Last Name & Degree
Dr. Rehana Bhorat
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Joung-Liang Lan
First Name & Middle Initial & Last Name & Degree
Dr. Joung-Liang Lan
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.kezarlifesciences.com
Description
Corporate website
Learn more about this trial
A Study of Zetomipzomib (KZR-616) in Patients With Active Lupus Nephritis (PALIZADE)
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