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

Kezar Life Sciences

Status and phase: Enrolling; Phase 2

Conditions: Lupus Nephritis

Treatments: Drug: placebo; Drug: zetomipzomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05781750

KZR-616-202

Details and patient eligibility

About

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).

Full 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.

Enrollment: 279 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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279 participants in 3 patient groups, including a placebo group

zetomipzomib 30 mg + standard-of-care

Experimental group

Description:

Initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through 52 weeks of the treatment period.

Treatment:

Drug: zetomipzomib

zetomipzomib 60 mg + standard-of-care

Experimental group

Description:

Initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through 52 weeks of the treatment period.

Treatment:

Drug: zetomipzomib

placebo + standard-of-care

Placebo Comparator group

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.

Treatment:

Drug: placebo