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)

NCT05639114 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: CVAY736F123012022-002691-362023-508498-97-00
• Study Type: interventional
• Target: 436
• Locations: 19 countries
• Sites: 135

Brief 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).

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus; SLE; B cell depletion; SLEDAI-2K; BILAG-2004; SRI; ANA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Proportion of participants on monthly or quarterly ianalumab with no moderate or severe British Isles Lupus Assessment Group (BILAG) flare

  Baseline to Week 60

• 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

  Week 36 to Week 60

• Proportion of participants on monthly or quarterly ianalumab achieving BILAG-based Composite Lupus Assessment (BICLA)

  Week 60

• Proportion of participants on monthly or quarterly ianalumab achieving Lupus Low Disease Activity State (LLDAS)

  Week 60

• Time to first occurrence of SRI-4 (participants on ianalumab monthly or quarterly)

  Baseline to Week 60

Study Arms (3)

Ianalumab s.c. monthly

EXPERIMENTAL

Ianalumab s.c. monthly

Drug: Ianalumab

Ianalumab s.c. quarterly

EXPERIMENTAL

Ianalumab s.c. quarterly

Drug: Ianalumab

Placebo s.c. monthly

PLACEBO COMPARATOR

placebo s.c. monthly

Drug: Placebo

Interventions

Ianalumab DRUG

ianalumab s.c. monthly or quarterly

Also known as: VAY736

Ianalumab s.c. monthly; Ianalumab s.c. quarterly

Placebo DRUG

placebo s.c. monthly

Placebo s.c. monthly

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Prior treatment with ianalumab
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (135)

Pinnacle Research Group Llc

Anniston, Alabama, 36207, United States

Location

Providence Medical Center

Burbank, California, 91505, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

Millennium Clinical Trials

Westlake Village, California, 91361, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Clinical Res Of W Florida

Clearwater, Florida, 33765, United States

Location

GNP Research

Cooper City, Florida, 33024, United States

Location

Clinical Research of West Florida Inc

Tampa, Florida, 33603, United States

Location

Parris and Associates Rheumatology

Lawrenceville, Georgia, 30044, United States

Location

Chicago Clinical Research Inst

Chicago, Illinois, 60607, United States

Location

Robert A Hozman MD SC

Skokie, Illinois, 60076, United States

Location

Lake Cumberland Rheumatology and In

New Albany, Indiana, 47150, United States

Location

Henry Ford Health

Detroit, Michigan, 48202, United States

Location

Sahni Rheumatology and Therapy

West Long Branch, New Jersey, 07764, United States

Location

Paramount Med Rsrch and Consult LLC

Middleburg Heights, Ohio, 44130, United States

Location

University Of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Shelby Research LLC

Memphis, Tennessee, 38119, United States

Location

Accurate Clinical Research Research

Baytown, Texas, 77521, United States

Location

Novel Research LLC

Bellaire, Texas, 77401, United States

Location

Accurate Clinical Research

League City, Texas, 77573, United States

Location

Epic Medical Research

Red Oak, Texas, 75154, United States

Location

Novartis Investigative Site

San Miguel, Tucumán Province, T4000CBC, Argentina

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Novartis Investigative Site

San Miguel de Tucumán, 4000, Argentina

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Novartis Investigative Site

Fortaleza, Ceará, 60125-025, Brazil

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Novartis Investigative Site

Vitória, Espírito Santo, 29055 450, Brazil

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Novartis Investigative Site

Salvador, Estado de Bahia, 40150 150, Brazil

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Novartis Investigative Site

Salvador, Estado de Bahia, 40444 130, Brazil

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Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30150-221, Brazil

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Novartis Investigative Site

Curitiba, Paraná, 80030-110, Brazil

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Novartis Investigative Site

Recife, Pernambuco, 50740-900, Brazil

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Novartis Investigative Site

Niterói, Rio de Janeiro, 24020 096, Brazil

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Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 22211-230, Brazil

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Novartis Investigative Site

Barretos, São Paulo, 14784 400, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 01244-030, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

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Novartis Investigative Site

Salvador, 40323-010, Brazil

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Novartis Investigative Site

Plovdiv, 4002, Bulgaria

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Novartis Investigative Site

Rousse, 7002, Bulgaria

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Novartis Investigative Site

Sofia, 1680, Bulgaria

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Calgary, Alberta, T2N 4Z6, Canada

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Vancouver, British Columbia, V5Z 1L7, Canada

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Hamilton, Ontario, L8N 3Z5, Canada

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Toronto, Ontario, M5T 2S8, Canada

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Rimouski, Quebec, G5L 5T1, Canada

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Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

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Novartis Investigative Site

Guangzhou, Guangdong, 510080, China

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Novartis Investigative Site

Shantou, Guangdong, 515000, China

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Novartis Investigative Site

Haikou, Hainan, 570311, China

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Zhuzhou, Hunan, 412000, China

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Nanjing, Jiangsu, 210008, China

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Novartis Investigative Site

Suzhou, Jiangsu, 215004, China

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Nanchang, Jiangxi, 330006, China

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Pingxiang, Jiangxi, 337000, China

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Changchun, Jilin, 130021, China

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Linyi, Shandong, 276000, China

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Chengdu, Sichuan, 610041, China

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Ürümqi, Xinjiang, 830001, China

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Ningbo, Zhejiang, 315016, China

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Novartis Investigative Site

Wenzhou, Zhejiang, 325000, China

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Novartis Investigative Site

Beijing, 100069, China

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Novartis Investigative Site

Beijing, 100730, China

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Shanghai, 200127, China

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Novartis Investigative Site

Xinxiang, 453099, China

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Novartis Investigative Site

Barranquilla, Atlántico, 080020, Colombia

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Novartis Investigative Site

Bucaramanga, Santander Department, 680003, Colombia

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Cali, Valle del Cauca Department, 760046, Colombia

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Novartis Investigative Site

Brno, 638 00, Czechia

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Prague, 128 00, Czechia

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Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

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Novartis Investigative Site

Guatemala City, 01010, Guatemala

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Guatemala City, 01011, Guatemala

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Novartis Investigative Site

Székesfehérvár, Fejér, 8000, Hungary

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Budapest, 1036, Hungary

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Budapest, H-1083, Hungary

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Novartis Investigative Site

Gyula, 5700, Hungary

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Novartis Investigative Site

Zalaegerszeg, 8900, Hungary

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Novartis Investigative Site

Haifa, 3109601, Israel

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Novartis Investigative Site

Ramat Gan, 5265601, Israel

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Novartis Investigative Site

Nagoya, Aichi-ken, 4578510, Japan

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Novartis Investigative Site

Nagoya, Aichi-ken, 4578511, Japan

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Novartis Investigative Site

Sapporo, Hokkaido, 0608648, Japan

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Yokohama, Kanagawa, 222-0036, Japan

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Novartis Investigative Site

Yokohama, Kanagawa-ku, 236-0004, Japan

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Sendai, Miyagi, 9838512, Japan

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Bunkyo Ku, Tokyo, 1138431, Japan

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Novartis Investigative Site

Bunkyo Ku, Tokyo, 1138655, Japan

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Novartis Investigative Site

Bunkyo-ku, Tokyo, 1138519, Japan

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Novartis Investigative Site

Chuo Ku, Tokyo, 1048560, Japan

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Novartis Investigative Site

Fuchū, Tokyo, 1838524, Japan

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Novartis Investigative Site

Itabashi-ku, Tokyo, 1738610, Japan

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Novartis Investigative Site

Meguro City, Tokyo, 153-8515, Japan

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Novartis Investigative Site

Shinjuku-ku, Tokyo, 1608582, Japan

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Novartis Investigative Site

Fukuoka, 8128582, Japan

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Novartis Investigative Site

Miyazaki, 889-1692, Japan

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Osaka, 5458586, Japan

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Wroclaw, Lower Silesian Voivodeship, 52-210, Poland

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Bydgoszcz, 85-065, Poland

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Novartis Investigative Site

Bydgoszcz, 85-168, Poland

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Novartis Investigative Site

Bytom, 41 902, Poland

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Novartis Investigative Site

Lodz, 90-338, Poland

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Novartis Investigative Site

Warsaw, 00-874, Poland

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Novartis Investigative Site

Warsaw, 04-141, Poland

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Novartis Investigative Site

Braga, 4710243, Portugal

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Novartis Investigative Site

Lisbon, 1050-034, Portugal

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Novartis Investigative Site

Lisbon, 1349-019, Portugal

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Novartis Investigative Site

Lisbon, 1649-035, Portugal

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Novartis Investigative Site

Vila Nova de Gaia, 4434 502, Portugal

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Novartis Investigative Site

Bratislava, 811 08, Slovakia

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Novartis Investigative Site

Košice, 040 01, Slovakia

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Novartis Investigative Site

Košice, 040 11, Slovakia

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Novartis Investigative Site

Pretoria, Gauteng, 0002, South Africa

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Cape Town, Western Cape, 7405, South Africa

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Novartis Investigative Site

Cape Town, Western Cape, 7500, South Africa

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Stellenbosch, Western Cape, 7600, South Africa

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Novartis Investigative Site

Umhlanga, 4320, South Africa

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Santiago Compostela, A Coruna, 15706, Spain

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Novartis Investigative Site

Elche, Alicante, 03203, Spain

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Novartis Investigative Site

Badalona, Barcelona, 08916, Spain

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Novartis Investigative Site

Santander, Cantabria, 39008, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

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Novartis Investigative Site

San Sebastian Reyes, Madrid, 28702, Spain

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Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

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Novartis Investigative Site

Vigo, Pontevedra, 36214, Spain

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Novartis Investigative Site

Barcelona, 08035, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Valencia, 46014, Spain

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Novartis Investigative Site

Valladolid, 47012, Spain

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Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

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Novartis Investigative Site

Muang, Thailand, 12120, Thailand

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Bangkok, 10700, Thailand

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Novartis Investigative Site

Ankara, Bilkent Cankaya, 06800, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, Etlik, 06010, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, Umraniye, 34766, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

ianalumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The trial is designed to 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).

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: December 6, 2022
• Study Start: March 2, 2023
• Primary Completion (Estimated): March 24, 2027
• Study Completion (Estimated): March 21, 2029
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

GU (2); ZA (5); HU (5); ES (12); CA (5); IL (2); SL (3); PT (5); US (22); BU (3); PL (7); AR (2); TH (4); CO (3); CZ (3); JP (17); CN (19); BR (13); TU (3)