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

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ClinicalTrials.gov Identifier: NCT05781750
Recruitment Status : Recruiting
First Posted : March 23, 2023
Last Update Posted : June 17, 2024
Sponsor:
Information provided by (Responsible Party):
Kezar Life Sciences, Inc.

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).

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: zetomipzomib Drug: placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 279 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 3, 2023
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : July 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: zetomipzomib 30 mg + standard-of-care
Initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through 52 weeks of the treatment period.
Drug: zetomipzomib
Subcutaneous injection of zetomipzomib
Other Name: KZR-616

Experimental: zetomipzomib 60 mg + standard-of-care
Initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through 52 weeks of the treatment period.
Drug: zetomipzomib
Subcutaneous injection of zetomipzomib
Other Name: KZR-616

Placebo Comparator: placebo + standard-of-care
Initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through 52 weeks of the treatment period.
Drug: placebo
Subcutaneous injection of placebo
Other Name: matching placebo




Primary Outcome Measures :
  1. To evaluate the efficacy of zetomipzomib [ Time Frame: Baseline through Week 37 ]

    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.

  2. To evaluate safety of zetomipzomib [ Time Frame: Baseline through Week 56 ]
    Incidence and severity of adverse event (AE)s for each treatment group and patients treated with zetomipzomib compared with placebo


Secondary Outcome Measures :
  1. Partial Renal Remission (PRR) [ Time Frame: Baseline through Week 25, Week 37, and Week 53 ]

    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.

  2. CRR [ Time Frame: Baseline through Week 25 and Week 53 ]
    Proportion of patients achieving CRR


Other Outcome Measures:
  1. Change in UPCR [ Time Frame: Baseline through Week 53 ]
    Percentage change from Baseline in UPCR by visit

  2. Time to event [ Time Frame: Baseline through Week 53 ]
    Time to CRR, PRR, death or renal events

  3. CRR and successful prednisone taper [ Time Frame: Baseline through Week 25, Week 37, and Week 53 ]
    Proportion of patients achieving CRR with successful taper of prednisone or equivalent by Week 17

  4. CRR and no prednisone use [ Time Frame: Baseline through Week 25, Week 37, and Week 53 ]
    Proportion of patients achieving CRR with no use of prednisone or equivalent during the 8 weeks prior to renal response assessment

  5. UPCR ≤0.5 [ Time Frame: Baseline through Week 13, Week 25, Week 37, and Week 53 ]
    Proportion of patients with UPCR ≤0.5

  6. CRR with UPCR ≤ ULN [ Time Frame: Baseline through Week 25, Week 37, and Week 53 ]
    Proportion of patients achieving CRR with UPCR ≤ Upper Limit of Normal

  7. Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) [ Time Frame: Baseline through Week 56 ]
    Changes from Baseline in clinical SLEDAI-2K score. The SLEDAI-2K score falls between 0 and 105. A higher score represents greater disease activity.

  8. Change in Patient-reported Outcomes [ Time Frame: Baseline through Week 56 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05781750


Contacts
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Contact: Kezar Life Sciences, Inc (650) 640-4480 PALIZADE@kezarbio.com

Locations
Show Show 149 study locations
Sponsors and Collaborators
Kezar Life Sciences, Inc.
Investigators
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Principal Investigator: Steven Kimmel, MD West Broward Rheumatology Associates, Inc.
Principal Investigator: Sumit Kumar, MD Texas Kidney Institute
Principal Investigator: Amarilis Gonzalez, MD Phoenix Research Center, LLC
Principal Investigator: David Tietjen, MD Nephrology Consultants, LLC
Additional Information:
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Responsible Party: Kezar Life Sciences, Inc.
ClinicalTrials.gov Identifier: NCT05781750    
Other Study ID Numbers: KZR-616-202
First Posted: March 23, 2023    Key Record Dates
Last Update Posted: June 17, 2024
Last Verified: June 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kezar Life Sciences, Inc.:
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)
Additional relevant MeSH terms:
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Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases