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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03393013
Registration number
NCT03393013
Ethics application status
Date submitted
21/12/2017
Date registered
8/01/2018
Date last updated
8/03/2024
Titles & IDs
Public title
A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis
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Scientific title
A Phase 1b/2 Study of KZR-616 in Patients With Systemic Lupus Erythematosus With and Without Nephritis (MISSION)
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Secondary ID [1]
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KZR-616-002
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Universal Trial Number (UTN)
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Trial acronym
MISSION
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Lupus Nephritis
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Systemic Lupus Erythematosus
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Condition category
Condition code
Renal and Urogenital
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Other renal and urogenital disorders
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Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - KZR-616
Experimental: KZR-616 45 mg + standard of care therapy (Phase 1b) - Dose 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.
Experimental: KZR-616 60 mg + standard of care therapy (Phase 1b) - Dose 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.
Experimental: KZR-616 75 mg + standard of care therapy (Phase 1b) - Dose 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.
Experimental: KZR-616 60 mg + standard therapy (Phase 2) - 60 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
Treatment: Drugs: KZR-616
Subcutaneous Injection of KZR-616
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event
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Assessment method [1]
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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.
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Timepoint [1]
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25 weeks
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Primary outcome [2]
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Phase 2: Number of Patients With Lupus Nephritis With a 50% Reduction in UPCR
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Assessment method [2]
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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.
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Timepoint [2]
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24 weeks
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Secondary outcome [1]
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Phase 1b: PK of KZR-616 (Cmax)
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Assessment method [1]
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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.
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Timepoint [1]
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8 hours
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Secondary outcome [2]
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Phase 1b: PK of KZR-616 (Tmax)
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Assessment method [2]
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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.
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Timepoint [2]
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8 hours
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Secondary outcome [3]
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Phase 1b: PK of KZR-616 (AUC)
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Assessment method [3]
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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.
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Timepoint [3]
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8 hours
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Secondary outcome [4]
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Phase 2: Number of Patients With a Partial Renal Response
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Assessment method [4]
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Number of patients with a partial renal response (PRR) after 24 weeks of treatment, as defined by:
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))
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%
No use of prohibited medication
Count of patients below includes those who satisfy all three of the above criteria.
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Timepoint [4]
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24 weeks
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Secondary outcome [5]
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Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks
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Assessment method [5]
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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.
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Timepoint [5]
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37 weeks
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Secondary outcome [6]
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Phase 1b: Recommended Phase 2 Doses of Zetomipzomib When Administered as a Subcutaneous Injection
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Assessment method [6]
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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.
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Timepoint [6]
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25 weeks
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Eligibility
Key inclusion criteria
Key
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
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Minimum age
18
Years
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Maximum age
75
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
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
- 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
20/02/2018
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
4/08/2022
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Sample size
Target
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Accrual to date
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Final
69
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Monash Health - Clayton
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Recruitment hospital [2]
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The Royal Melbourne Hospital - Parkville
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Recruitment postcode(s) [1]
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3168 - Clayton
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment outside Australia
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United States of America
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California
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United States of America
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Florida
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United States of America
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Iowa
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Colombia
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Atlantico
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Colombia
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Bucaramanga
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Colombia
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Santander
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Colombia
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Valle Del Cauca
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Mexico
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Jalisco
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Mexico
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Nuevo Leon
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Mexico
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Mexico City
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Peru
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La Libertad
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Peru
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Lima
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Poland
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Lódz
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Russian Federation
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Kemerovo
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Russian Federation
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Togliatti
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Ukraine
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State/province [21]
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Kyiv Governorate
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Kezar Life Sciences, Inc.
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Address
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Ethics approval
Ethics application status
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Summary
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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03393013
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Kezar
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Address
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Kezar Life Sciences, Inc.
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03393013
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