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Lupus NephritisPhase 1/2MISSIONNCT03393013

A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis

A Phase 1/2 study testing KZR-616 in people with Lupus Nephritis and Systemic Lupus Erythematosus, run by Kezar Life Sciences, Inc. at 36 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lupus Nephritis, Systemic Lupus Erythematosus
What is being tested?
KZR-616
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
36 sitesin 8 countries
Study dates
20 Feb 2018to 4 Aug 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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
  • Positive test at Screening for HIV, hepatitis B/C
  • Major surgery within 12 weeks before signing informed consent form or planned major surgery during the study period
  • Use of investigational therapy or device, and/or participation in an investigational trial <8 weeks or 5 half-lives, whichever is longer, prior to Baseline; Patients who participated in Phase 1b of KZR-616-002 are excluded from Phase 2

Trial locations and contacts

36 sites in 8 countries.

36 sites in 8 countries

United States17 sites

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • MedResearch, Inc.

    El Paso, Texas, 79902

  • Northwell Health

    Great Neck, New York, 11021

  • Accurate Clinical Research, Inc.

    Houston, Texas, 77034

  • Accurate Clinical Management, LLC

    Houston, Texas, 77084

  • University of Iowa

    Iowa City, Iowa, 52242

  • Academic Medical Research Institute

    Los Angeles, California, 990022

  • Ramesh C. Gupta, MD

    Memphis, Tennessee, 38119

  • SouthCoast Research Center, Inc.

    Miami, Florida, 33136

  • Hope Clinical Trials, Inc.

    Miami, Florida, 33165

  • NYU Langone Orthopedic Center - Seligman Center for Advanced Therapeutics

    New York, New York, 10016

  • SC Nephrology & Hypertension Center, Inc.

    Orangeburg, South Carolina, 29118

  • Omega Research Maitland

    Orlando, Florida, 32808

  • Arthritis Center, Inc

    Palm Harbor, Florida, 34684

  • University of Rochester Medical Center

    Rochester, New York, 14620

  • Advent Health Medical Group

    Tampa, Florida, 33614

  • Inland Rheumatology Clinical Trials, Inc.

    Upland, California, 91786

Other trials in United States

Colombia5 sites

  • Centro Integral de Reumatologia de Caribe CIRCARIBE S.A.S

    Barranquilla, Atlántico, 080020

  • Clinica de la Costa

    Barranquilla, Atlántico, 080020

  • Servimed S.A.S.

    Bucaramanga, Santander Department, 680003

  • Clinica de Artritis Temprana

    Cali, Valle del Cauca Department, 076001

  • Medicity SAS

    Santander, Bucaramanga, 680003

Other trials in Colombia

Mexico4 sites

  • Centro Integral de Reumatologia SA de CV

    Guadalajara, Jalisco, 44160

  • Instituto Nacional de Cardiología Ignacio Chavez

    Mexico City, 14080

  • Instituto Nacional de Ciencias Médicas y Nutricion "Salvador Zubiran"

    Mexico City, 14080

  • Hospital Universitario Dr José Eleuterio Gonzalez

    Monterrey, Nuevo León, 64020

Other trials in Mexico

Peru3 sites

  • Investigaciones Clinicas SAC

    Lima, 15023

  • Unidad de Investigacion en Reumatologia e Inmunologia Clinica San Juan Bautista

    Lima, 15431

  • Centro de Investigación Clínica Trujillo E.I.R.L/ Clínica Peruano Americana S.A.

    Trujillo, La Libertad, 13011

Other trials in Peru

Russia3 sites

  • Kuzbass Clinical Hospital

    Kemerovo, 650066

  • Medical Center Revma-Med

    Kemerovo, 650070

  • Tolyatti City Clinical Hospital #1

    Tolyatti, 445009

Other trials in Russia

Australia2 sites

  • Monash Health

    Clayton, Victoria, 3168

  • The Royal Melbourne Hospital

    Parkville, Victoria, 3050

Other trials in Australia

Poland1 site

  • Bioclinica

    Lodz, 90-368

Other trials in Poland

Ukraine1 site

  • Harmoniya Krasy

    Kyiv, Kyiv Governorate, 01135

Other trials in Ukraine

About this study

Official title: A Phase 1b/2 Study of KZR-616 in Patients With Systemic Lupus Erythematosus With and Without Nephritis (MISSION)

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).

Read the detailed description

This was a Phase 1b/2, open-label, multi-center study in which patients received zetomipzomib administered as a SC injection weekly for either 13 weeks (Phase 1b) or for 24 weeks (Phase 2). In both phases, safety assessments continued for up to 12 weeks following the last dose of zetomipzomib.

Phase 1b was an open-label, multiple dose escalation study designed to evaluate the safety and tolerability of escalating doses of zetomipzomib when administered in addition to standard-of-care therapy in patients with SLE with or without nephritis. For each cohort, at least 6 patients were to be enrolled to assure the availability of at least 4 evaluable patients. Decisions to escalate, expand, or decrease the dose level or dosing frequency following the first 4 weeks of dosing for at least 4 evaluable patients in a cohort were made following review by a data monitoring committee (DMC).

The zetomipzomib formulations and doses administered by cohort in Phase 1b were:

  • Cohort 1: zetomipzomib frozen maleate, 45 mg weekly × 13 weeks
  • Cohort 2: zetomipzomib frozen maleate, 60 mg weekly × 13 weeks
  • Cohort 2a: zetomipzomib frozen maleate, 30 mg weekly × 2 weeks, followed by 45 mg weekly × 2 weeks, followed by 60 mg weekly × 9 weeks
  • Cohort 2b: zetomipzomib lyophile, 30 mg weekly × 1 week, followed by 60 mg weekly × 12 weeks
  • Cohort 2c: zetomipzomib lyophile, 30 mg weekly × 1 week, followed by 60 mg weekly × 12 weeks (tolerability strategies cohort)
  • Cohort 3: zetomipzomib lyophile, 30 mg weekly × 1 week, followed by 75 mg weekly × 12 weeks

The Phase 2 portion of the open-label study was designed to evaluate the renal response, safety, and tolerability of a single dose level (60 mg) of zetomipzomib administered weekly in addition to standard therapy in patients with active proliferative lupus nephritis (LN) (Class III or IV, with or without Class V disease) with a UPCR ≥1.0. Patients must have been on standard therapy for LN including at least 1 immunosuppressive agent. Zetomipzomib was administered as a SC injection weekly for 24 weeks (including a step up from an initial Week 1 dose of 30 mg).

Being tested
KZR-616
Keywords
immunoproteasome inhibition, selective proteasome inhibition, proteasome, lupus nephritis, lupus, nephritis, active proliferative lupus nephritis, open-label, systemic lupus erythematosus, lupus erythematosus
Medical subject headings
Lupus Nephritis, Lupus Erythematosus, Systemic, Nephritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KZR-616Drug

    Also called zetomipzomib

    Subcutaneous Injection of KZR-616

Study groups in NCT03393013
Study groupRoleWhat they receive
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.
Receives: Drug: KZR-616
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.
Receives: Drug: KZR-616
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.
Receives: Drug: KZR-616
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
Receives: Drug: KZR-616

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 25 weeks

  2. 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.

    Measured: 24 weeks

Secondary outcomes (6)

  1. Phase 1b: PK of KZR-616 (Cmax)

    This is the maximum observed plasma concentration (Cmax) observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose.

    Measured: 8 hours

  2. Phase 1b: PK of KZR-616 (Tmax)

    This is the time to maximum observed plasma concentration (tmax) observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose.

    Measured: 8 hours

  3. Phase 1b: PK of KZR-616 (AUC)

    This is the area under the curve (AUC) from predose through 8 hour postdose observed after administration of KZR-616 at Week 5. The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 5, 15, 30 minutes, 1, 2, 4, and 8 hours postdose.

    Measured: 8 hours

  4. Phase 2: Number of Patients With a Partial Renal Response

    Number of patients with a partial renal response (PRR) after 24 weeks of treatment, as defined by:

    1. For this outcome measure, Primary UPCR criterion was used (a 50% reduction of UPCR and reduction of UPCR to <1.0 if baseline UPCR was <3.0 (or reduction of UPCR to <3.0 if baseline was ≥3.0))
    2. eGFR of greater than or equal to 60 mL/min/1.73 m^2 or no worsening of eGFR from baseline of greater than or equal to 25%
    3. No use of prohibited medication

    Count of patients below includes those who satisfy all three of the above criteria.

    Measured: 24 weeks

  5. Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks

    Exposure adjusted adverse event incidence rate for Injection Site Reactions and Systemic Injection Reactions.

    For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting.

    Measured: 37 weeks

  6. Phase 1b: Recommended Phase 2 Doses of Zetomipzomib When Administered as a Subcutaneous Injection

    The safety data from Phase 1b were used to determine a recommended dose of zetomipzomib to administer to patients with active proliferative lupus nephritis in Phase 2 of this study. As pre-specified in the study protocol, this outcome measure was to be determined qualitatively through discussion of relevant information from the Phase 1b portion of the trial at a data monitoring committee meeting.

    Measured: 25 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jan 2018
  2. Study start20 Feb 2018
  3. Primary completion4 Aug 2022
  4. Study completion4 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03393013
Sponsor's protocol ID
KZR-616-002
Acronym
MISSION
Status last verified
Nov 2025
First submitted
21 Dec 2017
Last updated
18 Nov 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37528520

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing KZR-616 in people with Lupus Nephritis and Systemic Lupus Erythematosus, run by Kezar Life Sciences, Inc. at 36 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, Colombia, Mexico, Peru, Russia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event (time frame: 25 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03393013, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.

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