Systemic Lupus ErythematosusPhase 3SIRIUS-SLE 1NCT05639114
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)
A Phase 3 study testing Ianalumab in people with Systemic Lupus Erythematosus, run by Novartis Pharmaceuticals at 135 sites in 19 countries.
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). Read more about this study
- Who is it for?
- Ages 12 to 100 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Ianalumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 436 participants
- Where
- 135 sitesin 19 countries
- Study dates
- 2 Mar 2023to 23 Mar 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
135 sites in 19 countries.
135 sites in 19 countries
United States22 sites
Pinnacle Research Group Llc
Anniston, Alabama, 36207
University of Colorado
Aurora, Colorado, 80045
Accurate Clinical Research Research
Baytown, Texas, 77521
Novel Research LLC
Bellaire, Texas, 77401
Providence Medical Center
Burbank, California, 91505
Chicago Clinical Research Inst
Chicago, Illinois, 60607
Clinical Res Of W Florida
Clearwater, Florida, 33765
GNP Research
Cooper City, Florida, 33024
Henry Ford Health
Detroit, Michigan, 48202
University of California San Diego
La Jolla, California, 92093
Parris and Associates Rheumatology
Lawrenceville, Georgia, 30044
Accurate Clinical Research
League City, Texas, 77573
Shelby Research LLC
Memphis, Tennessee, 38119
Paramount Med Rsrch and Consult LLC
Middleburg Heights, Ohio, 44130
Lake Cumberland Rheumatology and In
New Albany, Indiana, 47150
Yale University School Of Medicine
New Haven, Connecticut, 06520
University Of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Epic Medical Research
Red Oak, Texas, 75154
Robert A Hozman MD SC
Skokie, Illinois, 60076
Clinical Research of West Florida Inc
Tampa, Florida, 33603
Sahni Rheumatology and Therapy
West Long Branch, New Jersey, 07764
Millennium Clinical Trials
Westlake Village, California, 91361
China19 sites
Novartis Investigative Site
Beijing, 100069
Novartis Investigative Site
Beijing, 100730
Novartis Investigative Site
Changchun, Jilin, 130021
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Guangzhou, Guangdong, 510000
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Novartis Investigative Site
Haikou, Hainan, 570311
Novartis Investigative Site
Linyi, Shandong, 276000
Novartis Investigative Site
Nanchang, Jiangxi, 330006
Novartis Investigative Site
Nanjing, Jiangsu, 210008
Novartis Investigative Site
Ningbo, Zhejiang, 315016
Novartis Investigative Site
Pingxiang, Jiangxi, 337000
Novartis Investigative Site
Shanghai, 200001
Novartis Investigative Site
Shantou, Guangdong, 515000
Novartis Investigative Site
Suzhou, Jiangsu, 215004
Novartis Investigative Site
Ürümqi, Xinjiang, 830001
Novartis Investigative Site
Wenzhou, Zhejiang, 325000
Novartis Investigative Site
Xinxiang, 453099
Novartis Investigative Site
Zhuzhou, Hunan, 412000
Japan17 sites
Novartis Investigative Site
Bunkyo Ku, Tokyo, 1138431
Novartis Investigative Site
Bunkyo Ku, Tokyo, 1138655
Novartis Investigative Site
Bunkyo-ku, Tokyo, 1138519
Novartis Investigative Site
Chuo Ku, Tokyo, 1048560
Novartis Investigative Site
Fuchū, Tokyo, 1838524
Novartis Investigative Site
Fukuoka, 8128582
Novartis Investigative Site
Itabashi-ku, Tokyo, 1738610
Novartis Investigative Site
Meguro City, Tokyo, 1538515
Novartis Investigative Site
Miyazaki, 8891692
Novartis Investigative Site
Nagoya, Aichi-ken, 4578510
Novartis Investigative Site
Nagoya, Aichi-ken, 4578511
Novartis Investigative Site
Osaka, 5458586
Novartis Investigative Site
Sapporo, Hokkaido, 0608648
Novartis Investigative Site
Sendai, Miyagi, 9838512
Novartis Investigative Site
Shinjuku-ku, Tokyo, 1608582
Novartis Investigative Site
Yokohama, Kanagawa, 2220036
Novartis Investigative Site
Yokohama, Kanagawa, 2360004
Brazil13 sites
Novartis Investigative Site
Barretos, São Paulo, 14784-400
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-221
Novartis Investigative Site
Curitiba, Paraná, 80030-110
Novartis Investigative Site
Fortaleza, Ceará, 60125-025
Novartis Investigative Site
Niterói, Rio de Janeiro, 24020-096
Novartis Investigative Site
Recife, Pernambuco, 50740-900
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 22211-230
Novartis Investigative Site
Salvador, Estado de Bahia, 40150-150
Novartis Investigative Site
Salvador, Estado de Bahia, 40444-130
Novartis Investigative Site
Salvador, 40323-010
Novartis Investigative Site
São Paulo, São Paulo, 01244-030
Novartis Investigative Site
São Paulo, São Paulo, 04038-002
Novartis Investigative Site
Vitória, Espírito Santo, 29055-450
Spain12 sites
Novartis Investigative Site
Badalona, Barcelona, 08916
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Elche, Alicante, 03203
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
San Sebastian Reyes, Madrid, 28702
Novartis Investigative Site
Santander, Cantabria, 39008
Novartis Investigative Site
Santiago Compostela, A Coruna, 15706
Novartis Investigative Site
Valencia, 46014
Novartis Investigative Site
Valladolid, 47012
Novartis Investigative Site
Vigo, Pontevedra, 36214
Poland7 sites
Novartis Investigative Site
Bydgoszcz, 85-065
Novartis Investigative Site
Bydgoszcz, 85-168
Novartis Investigative Site
Bytom, 41 902
Novartis Investigative Site
Lodz, 90-338
Novartis Investigative Site
Warsaw, 00-874
Novartis Investigative Site
Warsaw, 04-141
Novartis Investigative Site
Wroclaw, Lower Silesian Voivodeship, 52-210
Hungary5 sites
Novartis Investigative Site
Budapest, 1083
Novartis Investigative Site
Budapest, 1134
Novartis Investigative Site
Gyula, 5700
Novartis Investigative Site
Székesfehérvár, Fejér, 8000
Novartis Investigative Site
Zalaegerszeg, 8900
Portugal5 sites
Novartis Investigative Site
Braga, 4710-243
Novartis Investigative Site
Lisbon, 1050-034
Novartis Investigative Site
Lisbon, 1349-019
Novartis Investigative Site
Lisbon, 1649-035
Novartis Investigative Site
Vila Nova de Gaia, 4434-502
South Africa5 sites
Novartis Investigative Site
Cape Town, Western Cape, 7405
Novartis Investigative Site
Cape Town, Western Cape, 7500
Novartis Investigative Site
Pretoria, Gauteng, 0002
Novartis Investigative Site
Somerset West, Western Cape, 7130
Novartis Investigative Site
Umhlanga, 4320
Canada4 sites
Novartis Investigative Site
Calgary, Alberta, T2N 4Z6
Novartis Investigative Site
Rimouski, Quebec, G5L 5T1
Novartis Investigative Site
Toronto, Ontario, M5T 2S8
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1L7
Thailand4 sites
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Muang, Thailand, 12120
Novartis Investigative Site
Songkhla, Hat Yai, 90110
Bulgaria3 sites
Novartis Investigative Site
Plovdiv, Bulgaria, 4002
Novartis Investigative Site
Rousse, 7002
Novartis Investigative Site
Sofia, 1680
Colombia3 sites
Novartis Investigative Site
Barranquilla, Atlántico, 080020
Novartis Investigative Site
Bucaramanga, Santander Department, 680003
Novartis Investigative Site
Cali, Valle del Cauca Department, 760046
Czechia3 sites
Novartis Investigative Site
Brno, 638 00
Novartis Investigative Site
Prague, 128 00
Novartis Investigative Site
Uherské Hradiště, 686 01
Guatemala3 sites
Novartis Investigative Site
Guatemala City, Departamento de Guatemala, 01010
Novartis Investigative Site
Guatemala City, Departamento de Guatemala, 01011
Novartis Investigative Site
Guatemala City, 01010
Slovakia3 sites
Novartis Investigative Site
Bratislava, 811 08
Novartis Investigative Site
Košice, 040 01
Novartis Investigative Site
Košice, 040 11
Turkey (Türkiye)3 sites
Novartis Investigative Site
Ankara, Bilkent Cankaya, 06800
Novartis Investigative Site
Ankara, Etlik, 06010
Novartis Investigative Site
Istanbul, Umraniye, 34766
Argentina2 sites
Novartis Investigative Site
San Miguel, Tucumán Province, T4000CBC
Novartis Investigative Site
San Miguel de Tucumán, T4000AXL
Israel2 sites
Novartis Investigative Site
Haifa, 3109601
Novartis Investigative Site
Ramat Gan, 5265601
About this study
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)
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).
Read the detailed 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)
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Ianalumab, Placebo
- Keywords
- Systemic Lupus Erythematosus, SLE, B cell depletion, SLEDAI-2K, BILAG-2004, SRI, ANA
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IanalumabDrug
Also called VAY736
ianalumab s.c. monthly or quarterly
PlaceboDrug
placebo s.c. monthly
| Study group | Role | What they receive |
|---|---|---|
| Ianalumab s.c. monthly | Experimental | Ianalumab s.c. monthly Receives: Drug: Ianalumab |
| Ianalumab s.c. quarterly | Experimental | Ianalumab s.c. quarterly Receives: Drug: Ianalumab |
| Placebo s.c. monthly | Placebo comparator | placebo s.c. monthly Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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)
Measured: 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
Maintaining reduced CS dose from Week 36 to Week 60
Measured: Week 36 to Week 60
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
Measured: Week 60
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
Measured: Week 60
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
Measured: Baseline to Week 60
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
Measured: Week 36 to Week 60
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
Measured: Week 60
Proportion of participants on monthly or quarterly ianalumab achieving Short Form 36 (SF-36) Bodily Pain response
Achieving SF-36 Bodily Pain response
Measured: Week 60
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
Measured: Week 60
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
Measured: Baseline to Week 60
Number of participants with adverse events
To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly
Measured: Baseline to Week 60
Proportion of participants with anti-ianalumab antibodies in serum (ADA assay) over time
Immunogenicity of ianalumab s.c. monthly or quarterly
Measured: Baseline to Week 164
Ianalumab concentration in serum during the treatment and follow-up
Ianalumab concentration in serum
Measured: Baseline to week 164
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start2 Mar 2023
- Primary completion26 Mar 2027 (estimated)
- Study completion23 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 436 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05639114
- Sponsor's protocol ID
- CVAY736F12301
- Other IDs
- 2022-002691-36, 2023-508498-97-00, 2023
- Acronym
- SIRIUS-SLE 1
- Status last verified
- Oct 2026
- First submitted
- 4 Nov 2022
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com