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

Sponsor

Kezar Life Sciences, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05781750

Collaborator

(none)

279

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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).

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.

Study Design

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

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 Names: 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 Names: 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 Names: matching placebo

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 Names:

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 Names:

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 Names:

matching placebo

Outcome Measures

Primary Outcome Measures

To evaluate the efficacy of zetomipzomib [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.
To evaluate safety of zetomipzomib [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

Partial Renal Remission (PRR) [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.
CRR [Baseline through Week 25 and Week 53]
Proportion of patients achieving CRR

Other Outcome Measures

Change in UPCR [Baseline through Week 53]
Percentage change from Baseline in UPCR by visit
Time to event [Baseline through Week 53]
Time to CRR, PRR, death or renal events
CRR and successful prednisone taper [Baseline through Week 25, Week 37, and Week 53]
Proportion of patients achieving CRR with successful taper of prednisone or equivalent by Week 17
CRR and no prednisone use [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
UPCR ≤0.5 [Baseline through Week 13, Week 25, Week 37, and Week 53]
Proportion of patients with UPCR ≤0.5
CRR with UPCR ≤ ULN [Baseline through Week 25, Week 37, and Week 53]
Proportion of patients achieving CRR with UPCR ≤ Upper Limit of Normal
Change in the Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) [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.
Change in Patient-reported Outcomes [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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