Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)

Systemic Lupus Erythematosus Clinical Trial

— SIRIUS-SLE 2  

Official title:

A Randomized, Double-blind, Placebo-controlled Multicenter Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05624749
• Other study ID #: CVAY736F12302
• Secondary ID: 2022-002690-2920
• Status: Recruiting
• Phase: Phase 3
• Start date: April 21, 2023
• Est. completion date: January 23, 2029

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial will evaluate efficacy, safety and tolerability of ianalumab compared to placebo, given as monthly subcutaneous (s.c.) injection on top of standard-of-care (SoC) treatment in participants with active systemic lupus erythematosus (SLE).

Description:

A randomized, double-blind, placebo-controlled multicenter phase 3 study to evaluate efficacy, safety and tolerability of ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: January 23, 2029
• Est. primary completion date: January 26, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• ianalumab
ianalumab s.c. monthly
• placebo
placebo s.c. monthly

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	San Miguel	Buenos Aires
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Tucuman
Australia	Novartis Investigative Site	Maroochydore	Queensland
Australia	Novartis Investigative Site	St Leonards	New South Wales
Australia	Novartis Investigative Site	Victoria Park	Western Australia
Chile	Novartis Investigative Site	Concepcion
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago	RM
Chile	Novartis Investigative Site	Valdivia	Los Rios
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Colombia	Novartis Investigative Site	Cundinamarca
Colombia	Novartis Investigative Site	Medellin	Antioquia
France	Novartis Investigative Site	Angers Cedex 9
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Montpellier Cedex 5
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris 13
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Toulouse 4
France	Novartis Investigative Site	Tours
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Kozhikode	Kerala
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Puducherry
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Secunderabad	Telangana
India	Novartis Investigative Site	Visakhapatnam
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Caserta	CE
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Torino	TO
Korea, Republic of	Novartis Investigative Site	Daejeon	Korea
Korea, Republic of	Novartis Investigative Site	Gwangju Gwangyeoksi
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Malaysia	Novartis Investigative Site	Ipoh	Perak
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Petaling Jaya	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Selangor Darul Ehsan
Malaysia	Novartis Investigative Site	Seremban	Negeri Sembilan
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Leon	Guanajuato
Mexico	Novartis Investigative Site	Merida	Yucatan
Mexico	Novartis Investigative Site	Mexico
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj-Napoca
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
United Kingdom	Novartis Investigative Site	Leicester
United States	Pinnacle Research Group LLC .	Anniston	Alabama
United States	Emory University .	Atlanta	Georgia
United States	University Of Maryland Rheumatology	Baltimore	Maryland
United States	Novel Research LLC	Bellaire	Texas
United States	Ahmed Arif Medical Research Center	Grand Blanc	Michigan
United States	Illinois Bone And Joint Institute	Hinsdale	Illinois
United States	University of Calif Irvine Med Cntr	Irvine	California
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Advanced Medical Research	La Palma	California
United States	Accurate Clinical Research Research	Lake Charles	Louisiana
United States	Bluegrass Community Research Inc	Lexington	Kentucky
United States	Homestead Associates in Research Inc	Miami	Florida
United States	Thomas Jefferson University Einstein Healthcare Network	Philadelphia	Pennsylvania
United States	Integral Rheumatology and Immunology Specialists IRIS	Plantation	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Chile,  Colombia,  France,  Germany,  India,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Romania,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)	SRI-4 response is defined as: Systemic Lupus Erythematosus Disease Activity Index - 2000 (SLEDAI-2K) reduction from baseline of = 4 points; No British Isles Lupus Assessment Group-2004 (BILAG-2004) worsening, defined as = 1 new A or = 2 new B items compared to baseline; No worsening in Physician Global Assessment of Disease Activity (PhGA), defined as an increase of = 0.3 from baseline on a 0 to 3 visual analog scale	Week 60
Secondary	Proportion of participants with no moderate or severe BILAG flare	Moderate BILAG flare is defined as 2 or more new BILAG-2004 B items compared to the previous visit; severe BILAG flare is defined as 1 or more new BILAG-2004 A items compared to the previous visit	Baseline to Week 60
Secondary	Proportion of participants maintaining between Week 36 and Week 60 a reduced corticosteroid (CS) dose of predniso(lo)ne = 5 mg/day or = baseline dose, whichever is lower	Maintaining reduced CS dose from Week 36 to Week 60	Week 36 to Week 60
Secondary	Proportion of participants achieving BILAG-based Composite Lupus Assessment (BICLA)	BICLA response is defined as: Reduction of all baseline BILAG-2004 A to B/C/D and baseline B to C/D and no worsening in other organ systems defined as = 1 new A or = 2 new B items compared to baseline; No worsening from baseline in SLEDAI-2K defined as an increase from baseline of > 0 points; No worsening in PhGA defined as an increase of = 0.3 from baseline on a 0 to 3 PhGA visual analog scale	Week 60
Secondary	Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)	LLDAS response is defined as: SLEDAI-2K = 4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) (Golder et al 2019); No new lupus disease activity compared with the previous assessment, defined as any new SLEDAI-2K component that was not present at the previous assessment; PhGA (scale 0-3) = 1; Current predniso(lo)ne (or equivalent) dose = 7.5 mg daily; Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents	Week 60
Secondary	Time to first occurrence of SRI-4	Time to first occurrence of SRI-4 from baseline to Week 60	Baseline to Week 60
Secondary	Proportion of participants achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced CS dose of predniso(lo)ne = 5 mg/day or = baseline dose, whichever is lower	Achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced CS dose of predniso(lo)ne = 5 mg/day or = baseline dose, whichever is lower	Week 36 to Week 60
Secondary	Proportion of participants achieving SRI-6	SRI-6 response is defined as: SLEDAI-2K reduction from baseline of = 6 points; No BILAG-2004 worsening, defined as = 1 new A or = 2 new B items compared to baseline; No worsening in PhGA, defined as an increase of = 0.3 from baseline on a 0 to 3 visual analog scale	Week 60
Secondary	Proportion of participants achieving SF-36 Bodily Pain response	Achieving Short Form 36 (SF-36) Bodily Pain response	Week 60
Secondary	Proportion of participants with Adverse Events (AEs)	To evaluate safety and tolerability of ianalumab s.c. monthly	Baseline to Week 60
Secondary	Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time	To evaluate immunogenicity of ianalumab s.c. monthly	Baseline to Week 164
Secondary	Ianalumab concentration in serum during the treatment and follow-up	Concentration of Ianalumab in serum	Baseline to Week 164