A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis
MISSION
A Phase 1b/2 Study of KZR-616 in Patients With Systemic Lupus Erythematosus With and Without Nephritis (MISSION)
1 other identifier
interventional
69
8 countries
36
Brief Summary
This was a Phase 1b/2, multi-center study in which patients received KZR-616, administered as a subcutaneous (SC) injection weekly for 13 weeks (Phase 1b) or 24 weeks (Phase 2).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2018
Longer than P75 for phase_1
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 21, 2017
CompletedFirst Posted
Study publicly available on registry
January 8, 2018
CompletedStudy Start
First participant enrolled
February 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 4, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 4, 2022
CompletedResults Posted
Study results publicly available
March 8, 2024
CompletedNovember 18, 2025
November 1, 2025
4.5 years
December 21, 2017
November 21, 2023
November 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event
The safety and tolerability of zetomipzomib (KZR-616) when administered as a subcutaneous injection weekly for 13 weeks in adult patients with systemic lupus erythematous (SLE) with and without nephritis, as assessed by number of patients who experienced at least one treatment-related treatment-emergent adverse event. For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting.
25 weeks
Phase 2: Number of Patients With Lupus Nephritis With a 50% Reduction in UPCR
To assess the number of patients with lupus nephritis with a 50% reduction in UPCR after 24 weeks of weekly SC injections with KZR-616 when compared to baseline.
24 weeks
Secondary Outcomes (6)
Phase 1b: PK of KZR-616 (Cmax)
8 hours
Phase 1b: PK of KZR-616 (Tmax)
8 hours
Phase 1b: PK of KZR-616 (AUC)
8 hours
Phase 2: Number of Patients With a Partial Renal Response
24 weeks
Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks
37 weeks
- +1 more secondary outcomes
Study Arms (4)
KZR-616 45 mg + standard of care therapy (Phase 1b)
EXPERIMENTALDose escalation cohort of patients with SLE with and without nephritis to receive 45 mg dose level of KZR-616 in combination with standard of care therapy. Two Phase 1b cohorts received 45 mg at some point during the study. Cohort 1 received 45 mg zetomipzomib frozen maleate weekly for 13 weeks. Cohort 2a followed a step-up dosing procedure. Patients received zetomipzomib frozen maleate, 30 mg weekly for 2 weeks, followed by 45 mg weekly for 2 weeks then followed by 60 mg weekly for 9 weeks. KZR-616 was administered as a SC injection.
KZR-616 60 mg + standard of care therapy (Phase 1b)
EXPERIMENTALDose escalation cohort of patients with SLE with and without nephritis to receive 60 mg dose level of KZR-616 in combination with standard of care therapy. Four Phase 1b cohorts received 60 mg at some point during the study. Cohort 2 received 60 mg zetomipzomib frozen maleate weekly for 13 weeks. Cohorts 2a, 2b, and 2c all followed a step-up dosing procedure. Patients in Cohort 2a received zetomipzomib frozen maleate, 30 mg weekly for 2 weeks, followed by 45 mg weekly for 2 weeks then followed by 60 mg weekly for 9 weeks. Patients in Cohort 2b received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 60 mg weekly for 12 weeks. Patients in Cohort 2c (tolerability strategies cohort) received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 60 mg weekly for 12 weeks. KZR-616 was administered as a SC injection.
KZR-616 75 mg + standard of care therapy (Phase 1b)
EXPERIMENTALDose escalation cohort of patients with SLE with and without nephritis to receive 75 mg dose level of KZR-616 in combination with standard of care therapy. One Phase 1b cohort received 75 mg at some point during the study. Cohort 3 followed a step-up dosing procedure. Patients in Cohort 3 received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 75 mg weekly for 12 weeks. KZR-616 was administered as a SC injection.
KZR-616 60 mg + standard therapy (Phase 2)
EXPERIMENTAL60 mg dose level of KZR-616 selected based on data from the phase 1b dose escalation and administered to patients with active lupus nephritis in combination with standard therapy including at least one immunosuppressive agent. KZR-616 was administered as a SC injection weekly at a dose of 60 mg for 24 weeks (including a step-up from an initial Week 1 dose of 30 mg). \*\* See Limitations/Caveats for additional information
Interventions
Subcutaneous Injection of KZR-616
Eligibility Criteria
You may qualify if:
- Phase 1b:
- Fulfilled the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification for SLE
- Had a positive antinuclear antibody (ANA) titer, anti-double stranded DNA (dsDNA) antibody titer, or a positive anti-Smith antibody titer
- Had active SLE (as indicated by Systemic Lupus Erythematosus Disease Activity Index 2000 \[SLEDAI-2K\] score ≥4), and
- Had received at least 1 prior therapy for SLE
- Phase 2:
- Had active proliferative LN (Class III or IV, with or without Class V disease)
- Had a UPCR ≥1.0 measured in 24-hour urine collection
- Had a histologic diagnosis of LN on renal biopsy within the prior 2 years; for biopsies \> 1 year before the Screening visit, one of the following must also be present at screening: low C3, low C4, or anti-ds-DNA elevated to above normal range
- Fulfilled the 2012 SLICC classification for SLE
- Had a positive ANA titer, anti-dsDNA antibody titer, or anti-Smith antibody titer, and
- Were currently receiving ≥1 immunosuppressive agent at a stable dose and route of administration for ≥8 weeks. If the patient is also on corticosteroids then must be on a stable dose for ≥ 2 weeks prior to Baseline
You may not qualify if:
- Phase 1b:
- Current or medical history of:
- Central nervous system manifestations by autoimmune disease
- Overlapping autoimmune condition that may affect study assessments/outcomes
- Antiphospholipid syndrome with history of thromboembolic event of within the 52 weeks prior to Screening
- Malignancy of any type, with exceptions for in situ cancer that has been completely excised and certain cancers \>5 years ago
- Positive test at Screening for HIV, hepatitis B/C
- Major surgery within 4 weeks before signing informed consent form or planned major surgery during the study period
- Phase 2:
- 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
- Malignancy of any type within the last 5 years, with exceptions for appropriately excised and cured cervical carcinoma in situ or excised basal or squamous cell carcinomas of the skin
- Has received dialysis within the 52 weeks prior to Screening
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
Academic Medical Research Institute
Los Angeles, California, 990022, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786, United States
SouthCoast Research Center, Inc.
Miami, Florida, 33136, United States
Hope Clinical Trials, Inc.
Miami, Florida, 33165, United States
Omega Research Maitland
Orlando, Florida, 32808, United States
Arthritis Center, Inc
Palm Harbor, Florida, 34684, United States
Advent Health Medical Group
Tampa, Florida, 33614, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Northwell Health
Great Neck, New York, 11021, United States
NYU Langone Orthopedic Center - Seligman Center for Advanced Therapeutics
New York, New York, 10016, United States
University of Rochester Medical Center
Rochester, New York, 14620, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
SC Nephrology & Hypertension Center, Inc.
Orangeburg, South Carolina, 29118, United States
Ramesh C. Gupta, MD
Memphis, Tennessee, 38119, United States
MedResearch, Inc.
El Paso, Texas, 79902, United States
Accurate Clinical Research, Inc.
Houston, Texas, 77034, United States
Accurate Clinical Management, LLC
Houston, Texas, 77084, United States
Monash Health
Clayton, Victoria, 3168, Australia
The Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Centro Integral de Reumatologia de Caribe CIRCARIBE S.A.S
Barranquilla, Atlántico, 080020, Colombia
Clinica de la Costa
Barranquilla, Atlántico, 080020, Colombia
Medicity SAS
Santander, Bucaramanga, 680003, Colombia
Servimed S.A.S.
Bucaramanga, Santander Department, 680003, Colombia
Clinica de Artritis Temprana
Cali, Valle del Cauca Department, 076001, Colombia
Centro Integral de Reumatologia SA de CV
Guadalajara, Jalisco, 44160, Mexico
Hospital Universitario Dr José Eleuterio Gonzalez
Monterrey, Nuevo León, 64020, Mexico
Instituto Nacional de Cardiología Ignacio Chavez
Mexico City, 14080, Mexico
Instituto Nacional de Ciencias Médicas y Nutricion "Salvador Zubiran"
Mexico City, 14080, Mexico
Centro de Investigación Clínica Trujillo E.I.R.L/ Clínica Peruano Americana S.A.
Trujillo, La Libertad, 13011, Peru
Investigaciones Clinicas SAC
Lima, 15023, Peru
Unidad de Investigacion en Reumatologia e Inmunologia Clinica San Juan Bautista
Lima, 15431, Peru
Bioclinica
Lodz, 90-368, Poland
Kuzbass Clinical Hospital
Kemerovo, 650066, Russia
Medical Center Revma-Med
Kemerovo, 650070, Russia
Tolyatti City Clinical Hospital #1
Tolyatti, 445009, Russia
Harmoniya Krasy
Kyiv, Kyiv Governorate, 01135, Ukraine
Related Publications (1)
Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.
PMID: 37528520DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
In Phase 2, of note, prior to the adoption of the open-label study design to improve enrollment after the onset of the COVID-19 pandemic, 1 patient with active proliferative LN was enrolled in Phase 2 under the earlier randomized, placebo-controlled, double-blind design. This patient was randomized to zetomipzomib at a dose of 30 mg SC weekly for 13 weeks and completed 12 of 13 dose administrations and all protocol-required procedures.
Results Point of Contact
- Title
- Regulatory Affairs
- Organization
- Kezar Life Sciences, Inc
Study Officials
- STUDY DIRECTOR
Kezar
Kezar Life Sciences, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 21, 2017
First Posted
January 8, 2018
Study Start
February 20, 2018
Primary Completion
August 4, 2022
Study Completion
August 4, 2022
Last Updated
November 18, 2025
Results First Posted
March 8, 2024
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share