A PHASE 1B/2 STUDY OF KZR-616 IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS WITH AND WITHOUT NEPHRITIS

Not Applicable

Recruiting

• Conditions: -M32 Systemic lupus erythematosus; Systemic lupus erythematosus; M32

• Registration Number: PER-100-20
• Lead Sponsor: Kezar Life Sciences, INC.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-20
• Study Completion: 2022-08-04
• Last Update Posted: 20 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 6

Inclusion Criteria

1. Male or female patients aged 18 to 75 years (inclusive)

2. BMI of ≥ 18 kg/m2

3. Fulfills the 2012 SLICC classification criteria for SLE

4. At least one of the following at Screening per central lab:
a) Positive ANA test (1:80 or higher) or
b) Anti-dsDNA antibodies elevated to above normal (i.e., positive results); or
c) Anti-Smith antibody at screening elevated to above normal (i.e., positive results)

5. Active nephritis with UPCR ≥ 1.0 measured in 24-hour urine collection

6. Currently receiving one or more immunosuppressive agents (see Section 7.2 for allowed
background medications and Section 14.5, Appendix E for excluded medications) that has been
stable for dose and route of administration for ≥ 8 weeks prior to Baseline. If patient is also on
corticosteroids then must be on a stable dose for ≥ 2 weeks prior to Baseline

7. Renal biopsy within 2 years of the Screening visit with a histologic diagnosis of LN (ISN/RPS)
Classes III, IV-S or IV-G, (A) or (A/C) +/- Class V; 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.

8. Acceptable screening laboratory values:
a) Adequate hematologic criteria:
 Absolute neutrophil count ≥ 1.5 × 109/L (≥ 1 × 109/L if neutropenia is attributable
to lupus disease activity)
 White blood cells ≥ 2.0 × 109/L (≥ 1.5 × 109/L if leukopenia is attributable to
lupus disease activity)
 Absolute lymphocyte count ≥ 0.5 × 109/L
 Hgb ≥ 9 g/dL (≥ 8 g/dL if anemia is attributable to lupus disease activity)
 Platelet count ≥ 100 × 109/L (≥ 25 × 109/L if thrombocytopenia is attributable to
lupus disease activity)
b) Adequate hepatic function:
 Total bilirubin ≤ 1.5 × ULN (3 × ULN for patients with known Gilbert’s
syndrome)
 AST ≤ 2.5 × ULN
 ALT ≤ 2.5 × ULN
c) eGFR ≥ 30 mL/min/1.73 m2 estimated based on CKD-EPI formula
d) IgG ≥ 500 mg/dL

9. Female patients of childbearing potential must have a negative serum pregnancy test at Screening
and a negative urine pregnancy test at Baseline and must agree to employ adequate birth control
measures for the duration of the study. Women of childbearing potential (WOCBP) must use
highly effective and medically acceptable methods of contraception to prevent pregnancy during
Screening and must agree to continue to practice adequate contraception during the study and for
4 weeks after administration of the last dose of the study drug.
For the purposes of this study, WOCBP are defined as: all postpubescent female patients, unless
the patient is postmenopausal (defined by amenorrhea for at least 2 years or amenorrhea for at
least 1 year with confirmatory follicle stimulating hormone [FSH] level in the postmenopausal
range as documented historically or measured by the central laboratory at Screening and if patient
is not on supplementary hormonal therapy) or if the patient is surgically sterile (i.e., tubal
ligation, hysterectomy, bilateral salpingoophorectomy).
Highly effective contraception is defined as the use of an intrauterine device or hormonal
contraceptives (e.g., implant or oral), or having a vasec

Exclusion Criteria

1. Any of the following:
a) Dialysis within 12 months prior to Screening or expected need for renal replacement
therapy (dialysis or renal transplant) within a 6-month period after enrollment
b) Rapidly progressive glomerulonephritis (RPGN) and/or renal disease other than ISN/RPS
Classes III, IV-S or IV-G, [A] or [A/C] with or without Class V LN)
c) Chronic kidney disease not due to LN
d) > 50% sclerosed glomeruli on most recent renal biopsy

2. Presence of another rheumatic (overlap) disease that may confound clinical assessments in the
study. Secondary sicca or Sjogren’s syndrome and antiphospholipid antibody syndrome are
allowed

3. History of antiphospholipid syndrome with history of thromboembolic event within 12 months of
screening

4. Active central nervous system involvement by autoimmune disease (e.g., neuropsychiatric SLE
including seizures, psychosis, acute confusional state or cerebrovascular accident) requiring specific therapeutic intervention within 60 days prior to first day of study treatment. Headache treated only with acetaminophen, NSAIDs, or approved doses of triptans is permitted with medical monitor approval.

5. Active or chronic infection:
a) Acute or chronic bacterial or fungal infections:
 Requiring systemic antibiotic or antifungal therapy within 14 days of Screening
 Receipt of more than a 14-day course of antimicrobial therapy within 12 weeks
of Screening to treat sepsis, abscess, osteomyelitis, joint infection, or bacterial
endocarditis.
b) Acute viral illness:
 Signs and symptoms of acute viral illness must be resolved ≥ 4 weeks prior to
Day 1 (Baseline). Patients with history of SARS-CoV-2 must have full resolution
of symptoms and no evidence of associated renal injury
 Symptomatic herpes zoster or herpes simplex infection (HSV) (not including
simple oral HSV lesions) within 12 weeks prior to Screening or during the
Screening Period
 Acute hepatitis B or C infection
c) Chronic viral infection:
 Patients with chronic herpesvirus infections such as HSV or CMV should be on
suppressive therapy at Baseline and during the study.
 Chronic hepatitis C infection. Patients with prior chronic hepatitis C infection
should have received a full treatment course and have documented absence of
detectable HCV DNA at the completion of at least 12 weeks of treatment to be
enrolled.
 Chronic hepatitis B infection. Patients who are HBsAg negative and hepatitis B
core antibody positive with no detectable DNA will be allowed into the study and
will require regular monitoring of hepatitis B virus DNA. (see Section 8.2.6.6).
 Known seropositivity for or active infection with human immunodeficiency virus
(HIV). Those with a positive screening test and negative confirmatory test are
eligible.

6. Patient has or had any of the following:
a) Progressive multifocal leukoencephalopathy
b) Active or untreated latent TB, per QuantiFERON-TB Gold at screening per
Section 8.2.6.6
 Patients with a history of latent TB with documented completed treatment per
Centers for Disease Control and Prevention guidelines are allowed
 A chest x-ray must be performed during screening if one has not been done
within 12 weeks prior to the screening visit
c) Receipt

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:UPCR (urine protein to creatinine ratio)<br>Measure:The number of patients with a 50% reduction in UPCR after 24 weeks of treatment when compared to baseline<br>Timepoints:24 Weeks<br>