Phase 3 Study to Evaluate Two Regimens of Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 1)

Systemic Lupus Erythematosus Clinical Trial

— SIRIUS-SLE 1  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05639114
• Other study ID #: CVAY736F12301
• Secondary ID: 2022-002691-3620
• Status: Recruiting
• Phase: Phase 3
• Start date: March 2, 2023
• Est. completion date: January 16, 2029

Study information

• Verified date: May 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 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).

Description:

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 406
• Est. completion date: January 16, 2029
• Est. primary completion date: January 19, 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 or quarterly
• Placebo
placebo s.c. monthly

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	Barretos	Sao Paulo
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Brasilia	DF
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Niteroi	RJ
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Salvador
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	Vitoria	ES
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Ruse
Canada	Novartis Investigative Site	Rimouski	Quebec
China	Novartis Investigative Site	Baotou	Inner Mongolia
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Haikou	Hainan
China	Novartis Investigative Site	Linyi	Shandong
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Pingxiang	Jiangxi
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shantou	Guangdong
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Urumqi	Xinjiang
China	Novartis Investigative Site	Wuhan
China	Novartis Investigative Site	Zhejiang
China	Novartis Investigative Site	Zhuzhou	Hunan
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Uherske Hradiste
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Szekesfehervar	Fejer
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Ramat Gan
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Fuchu	Tokyo
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Gifu
Japan	Novartis Investigative Site	Ichikawa	Chiba
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kurashiki	Okayama
Japan	Novartis Investigative Site	Meguro	Tokyo
Japan	Novartis Investigative Site	Miyazaki-city	Miyazaki
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Ono	Hyogo
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Bytom
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw	Dolnoslaskie
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Leiria
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Piestany
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Stellenbosch
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Elche	Alicante
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Merida	Extremadura
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	San Sebastian de los Reyes	Madrid
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Santiago De Compostela	Galicia
Spain	Novartis Investigative Site	Valladolid	Castilla Y Leon
Spain	Novartis Investigative Site	Vigo	Pontevedra
Spain	Novartis Investigative Site	Vitoria Gasteiz	Pais Vasco
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Etlik / Ankara
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Konya
United States	University of Colorado University of Colorado Denver	Aurora	Colorado
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	Providence Medical Center	Burbank	California
United States	Clinical Research of West Florida	Clearwater	Florida
United States	STAT Research Inc .	Dayton	Ohio
United States	Henry Ford Health	Detroit	Michigan
United States	University of California San Diego .	La Jolla	California
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Parris and Associates Rheumatology	Lawrenceville	Georgia
United States	Accurate Clinical Research Research	League City	Texas
United States	Keck School of Medicine Keck Medicine of USC	Los Angeles	California
United States	Ramesh C Gupta MD Memphis TN	Memphis	Tennessee
United States	Paramount Med Rsrch and Consult LLC .	Middleburg Heights	Ohio
United States	Lake Cumberland Rheumatology and In	New Albany	Indiana
United States	Epic Medical Research	Red Oak	Texas
United States	Millennium Clinical Trials	Simi Valley	California
United States	Robert A Hozman MD SC	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Guatemala,  Hungary,  Israel,  Japan,  Poland,  Portugal,  Singapore,  Slovakia,  South Africa,  Spain,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants on monthly ianalumab 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 on monthly or quarterly ianalumab with no moderate or severe British Isles Lupus Assessment Group (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 on monthly or quarterly ianalumab 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 on monthly or quarterly ianalumab 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 on monthly or quarterly ianalumab 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).; 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 (participants on ianalumab monthly or quarterly)	Time to first occurrence of SRI-4 from baseline to Week 60	Baseline to Week 60
Secondary	Proportion of participants on monthly or quarterly ianalumab achieving SRI-4 at Week 60 while maintaining between Week 36 and Week 60 a reduced corticosteroid 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 on monthly or quarterly ianalumab 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 on monthly or quarterly ianalumab achieving Short Form 36 (SF-36) Bodily Pain response	Achieving SF-36 Bodily Pain response	Week 60
Secondary	Proportion of participants on quarterly ianalumab achieving SRI-4	SRI-4 response is defined as: SLEDAI-2K reduction from baseline of = 4 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 on monthly or quarterly ianalumab with Adverse Events (AEs) and Serious Adverse Events (SAEs)	To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly	Baseline to Week 60
Secondary	Number of participants with adverse events	To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly	Baseline to Week 60
Secondary	Proportion of participants with anti-ianalumab antibodies in serum (ADA assay) over time	Immunogenicity of ianalumab s.c. monthly or quarterly	Baseline to Week 164
Secondary	Ianalumab concentration in serum during the treatment and follow-up	Ianalumab concentration in serum	Baseline to week 164