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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03393013




Registration number
NCT03393013
Ethics application status
Date submitted
21/12/2017
Date registered
8/01/2018

Titles & IDs
Public title
A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis
Scientific title
A Phase 1b/2 Study of KZR-616 in Patients With Systemic Lupus Erythematosus With and Without Nephritis (MISSION)
Secondary ID [1] 0 0
KZR-616-002
Universal Trial Number (UTN)
Trial acronym
MISSION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lupus Nephritis 0 0
Systemic Lupus Erythematosus 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Patients Who Experienced at Least One Treatment-Related Treatment-Emergent Adverse Event
Timepoint [1] 0 0
25 weeks
Primary outcome [2] 0 0
Phase 2: Number of Patients With Lupus Nephritis With a 50% Reduction in UPCR
Timepoint [2] 0 0
24 weeks
Secondary outcome [1] 0 0
Phase 1b: PK of KZR-616 (Cmax)
Timepoint [1] 0 0
8 hours
Secondary outcome [2] 0 0
Phase 1b: PK of KZR-616 (Tmax)
Timepoint [2] 0 0
8 hours
Secondary outcome [3] 0 0
Phase 1b: PK of KZR-616 (AUC)
Timepoint [3] 0 0
8 hours
Secondary outcome [4] 0 0
Phase 2: Number of Patients With a Partial Renal Response
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
Phase 2: Safety and Tolerability of KZR-616 When Administered as a SC Injection Weekly for 24 Weeks
Timepoint [5] 0 0
37 weeks
Secondary outcome [6] 0 0
Phase 1b: Recommended Phase 2 Doses of Zetomipzomib When Administered as a Subcutaneous Injection
Timepoint [6] 0 0
25 weeks

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

Key
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/02/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/08/2022
Sample size
Target
Accrual to date
Final
69
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Health - Clayton
Recruitment hospital [2] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Colombia
State/province [9] 0 0
Atlantico
Country [10] 0 0
Colombia
State/province [10] 0 0
Bucaramanga
Country [11] 0 0
Colombia
State/province [11] 0 0
Santander
Country [12] 0 0
Colombia
State/province [12] 0 0
Valle Del Cauca
Country [13] 0 0
Mexico
State/province [13] 0 0
Jalisco
Country [14] 0 0
Mexico
State/province [14] 0 0
Nuevo Leon
Country [15] 0 0
Mexico
State/province [15] 0 0
Mexico City
Country [16] 0 0
Peru
State/province [16] 0 0
La Libertad
Country [17] 0 0
Peru
State/province [17] 0 0
Lima
Country [18] 0 0
Poland
State/province [18] 0 0
Lódz
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Kemerovo
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Togliatti
Country [21] 0 0
Ukraine
State/province [21] 0 0
Kyiv Governorate

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kezar Life Sciences, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kezar
Address 0 0
Kezar Life Sciences, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03393013