Last Update: Nov 19, 2024
A Randomized, Double-blind, Parallel Group, Placebo-controlled Multicenter Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of Two Regimens of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 1)
ClinicalTrials.gov Identifier:
Novartis Reference Number:CVAY736F12301
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The trial will evaluate efficacy, safety and tolerability of two regimens of ianalumab
compared to placebo, given as monthly or quarterly subcutaneous (s.c.) injection on top
of standard-of-care (SoC) treatment in participants with active systemic lupus
erythematosus (SLE). A randomized, double-blind, parallel group, placebo-controlled multicenter phase 3 study
to evaluate efficacy, safety and tolerability of two regimens of ianalumab on top of
standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 1)

Systemic Lupus Erythematosus
Phase3
Recruiting
406
Mar 02, 2023
Jan 16, 2029
All
12 Years - (Child, Adult, Older Adult)

Interventions

Drug

Ianalumab

ianalumab s.c. monthly or quarterly
Drug

Placebo

placebo s.c. monthly

Eligibility Criteria

Inclusion Criteria:

- Male and female participants aged 12 years or older at the time of screening, or
limited to 18 years or older in European Economic Area countries and other countries
where inclusion of participants below 18 years is not allowed.

- Diagnosis of systemic lupus erythematosus meeting the 2019 European League Against
Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria
at least 6 months prior to screening.

- Elevated serum titers at screening of anti-nuclear antibodies ≥ 1:80 as determined
by a central laboratory with a SLE-typical fluorescence pattern.

- Currently receiving CS and/or anti-malarial treatment and/or another
disease-modifying antirheumatic drug (DMARD) as specified in the protocol.

- SLEDAI-2K criteria at screening: SLEDAI-2K score ≥ 6 points, excluding points
attributed to "fever", "lupus headache", "alopecia", and "organic brain syndrome"

- BILAG-2004 disease activity level at screening of at least 1 of the following:

- BILAG-2004 level 'A' disease in ≥ 1 organ system, Or

- BILAG-2004 level 'B' disease in ≥ 2 organ systems

- Weigh at least 35 kg at screening

Exclusion Criteria:

- Prior treatment with ianalumab

- History of receiving following treatment: I) high dose CS, calcineurin inhibitors,
JAK or other kinase inhibitors or other DMARD (except as listed in inclusion
criteria) administered within 12 weeks prior to screening. II) cyclophosphamide or
biologics such as immunoglobulins (intravenous or s.c.), plasmapheresis, anti-type I
interferon receptor biologic agents, anti-CD40 agents, CTLA4-Fc Ig or B-cell
activating factor (BAFF)-targeting agents administered within 24 weeks prior to
screening; belimumab administered within 12 weeks prior to screening. III) any B
cell-depleting therapies, other than ianalumab administered within 36 weeks prior to
randomization or as long as B cell count is less than the lower limit of normal or
baseline value prior to receipt of B cell-depleting therapy (whichever is lower).
IV) Traditional Chinese medicines administered within 30 days prior to
randomization.

- Active viral, bacterial or other infections requiring intravenous or intramuscular
treatment for clinically significant infection

- Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)

- Evidence of active tuberculosis infection

- History of primary or secondary immunodeficiency, including a positive human
immunodeficiency virus (HIV) test result at screening

- Any one of the following abnormal laboratory values prior to randomization

- Platelets < 25000/mm^3 (< 25 x 10^3/μL)

- Hemoglobin (Hgb) < 8.0 g/dL (< 5 mmol/L), or < 7.0 g/dL (< 4.3 mmol/L) if
related to participant's SLE such as in active hemolytic anaemia

- Absolute neutrophil count (ANC) (< 0.8 x 10^3/ μL)

- Severe organ dysfunction or life-threatening disease at screening

- Presence of severe lupus kidney disease as defined by proteinuria above 2 g/day or
equivalent using spot urine protein creatinine ratio, or serum creatinine greater
than 2.0 mg/dL (176.84 µmol/L), or requiring immune-suppressive induction or
maintenance treatment at screening

- Receipt of live/attenuated vaccine within a 4-week period before first dosing

- Any uncontrolled, co-existing serious disease, which in the opinion of the
investigator will place the participant at risk for participation or interfere with
evaluation for SLE-related symptoms

- Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or
chronic treatment with systemic CS

- History of malignancy of any organ system other than localized basal cell carcinoma
of the skin or in situ cervical cancer

- Pregnant or nursing (lactating) women.

- Women of child-bearing potential (WOCBP), defined as all women physiologically
capable of becoming pregnant, unless they are using highly effective methods of
contraception while on study treatment and for 6 months after stopping of
investigational drug.

- Any surgical, medical, psychiatric or additional physical condition that may
jeopardize participation in this study

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