Lupus NephritisPhase 3SIRIUS-LNNCT05126277
Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis
A Phase 3 study testing ianalumab s.c. q4w and ianalumab s.c. q12w in people with Lupus Nephritis, run by Novartis Pharmaceuticals at 145 sites in 27 countries.
Trial summary
This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- ianalumab s.c. q4w and ianalumab s.c. q12w
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 452 participants
- Where
- 145 sitesin 27 countries
- Study dates
- 14 Jul 2022to 4 Feb 2031
- 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 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants eligible for inclusion in this study must meet all of the following criteria:
- Adult male and female participants aged 18 years or older at the time of screening
- Weigh at least 35 kg at screening
- Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria
- Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 at screening visit based on central or local laboratory result
- Active LN at screening, as defined by meeting the 3 following criteria:
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- Renal biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/exclusion criteria.
- UPCR ≥ 1.0 g/g on 24h urine collection at Screening
- eGFR ≥ 25mL/min/1.73 m2. Participants with eGFR < 30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in ≤ 50% of glomeruli
- Newly diagnosed participants as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA
- Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization
- Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications
- Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization
- Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior randomization. Participant who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day) oral predniso(lo)ne.
- Able to communicate well with the Investigator to understand and comply with the requirements of the study
Who cannot join
- Participants meeting any of the following criteria are not eligible for inclusion in this study:
- Severe renal impairment as defined by i.) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs) or ii.) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation
- Sclerosis in > 50% of glomeruli on renal biopsy
- Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline. Use of certain Traditional Chinese Medicines
- Prior use of ianalumab (ever); or prior use other B cell depleting therapy within 36 weeks prior to randomization or if therapy was administered < 36 weeks prior to randomization, B cell count less than the lower limit of normal or patient's own baseline value prior to having received an earlier B cell-depleting therapy
- Prior treatment with any of the following within 12 weeks prior to randomization
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- Belimumab, telitacicept, abatacept, TNF-α mAb, immunoglobulins (i.v./s.c.) plasmapheresis
- Any other immuno-suppressants (i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors)
- Thalidomide treatment and/or methotrexate
- Combination of DMARDs
- Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA
- Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization
- History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation
- Any one of the following laboratory values at screening:
- Hemoglobin levels < 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
- Platelet count < 25 x 1000/µL
- Absolute neutrophil count (ANC) < 0.8 x 1000/µL
- Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.
- History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients
- Receipt of live/attenuated vaccine within a 4-week period prior to randomization
- History of primary or secondary immunodeficiency, including a positive HIV test result
- History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the participants in case of participation in this study
- Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant
- Evidence of active tuberculosis (TB) infection (after anti-TB treatment, participants with history of TB may become eligible according to national local guidelines)
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after stopping of investigational medication
- Sexually active male participants, who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment
- Other protocol -defined Inclusion/Exclusion may apply.
Trial locations and contacts
145 sites in 27 countries.
145 sites in 27 countries
China26 sites
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Binzhou, Shandong, 256603
Novartis Investigative Site
Changchun, Jilin, 130041
Novartis Investigative Site
Changsha, Hunan, 410008
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Chongqing, 400038
Novartis Investigative Site
Guangzhou, Guangdong, 510000
Novartis Investigative Site
Guangzhou, Guangdong, 510080
Novartis Investigative Site
Guangzhou, Guangdong, 510120
Novartis Investigative Site
Guangzhou, 510080
Novartis Investigative Site
Guangzhou, 510280
Novartis Investigative Site
Haikou, Hainan, 570311
Novartis Investigative Site
Linyi, Shandong, 276000
Novartis Investigative Site
Liuzhou, Guangxi, 545005
Novartis Investigative Site
Nanchang, Jiangxi, 330006
Novartis Investigative Site
Nanjing, Jiangsu, 210029
Novartis Investigative Site
Ningbo, Zhejiang, 315016
Novartis Investigative Site
Shanghai, 200001
Novartis Investigative Site
Shanghai, 200040
Novartis Investigative Site
Shanghai, 200080
Novartis Investigative Site
Shantou, Guangdong, 515000
Novartis Investigative Site
Shenyang, Liaoning, 110004
Novartis Investigative Site
Shenzhen, Guangdong, 518037
Novartis Investigative Site
Wuhan, Hubei, 430022
Novartis Investigative Site
Wuhan, Hubei, 430060
Novartis Investigative Site
Xian, Shanxi, 710004
United States25 sites
Emory University School of Medicine
Atlanta, Georgia, 30303
Fides Clinical Research
Atlanta, Georgia, 30342
University Of Alabama
Birmingham, Alabama, 35294
University Of Cincinnati
Cincinnati, Ohio, 45267
NY Nephrology
Clifton Park, New York, 12065
Precision Comprehensive Research
Colleyville, Texas, 76034
Univof Texas Southwestern Med Cntr
Dallas, Texas, 75235
Wayne State University
Detroit, Michigan, 48201
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Advanced Medical Research
La Palma, California, 90623
Accurate Clinical Research
Lake Charles, Louisiana, 70601
Univ of Nevada School of Med
Las Vegas, Nevada, 89102
Parris and Associates Rheumatology
Lawrenceville, Georgia, 30044
Uni Wisconsin School Med Pub Health
Madison, Wisconsin, 53792
University Of Miami
Miami, Florida, 33136
UMC New Orleans
New Orleans, Louisiana, 70112
Hospital for Special Surgery
New York, New York, 10021
Northwell Health
New York, New York, 10028
University of California Irvine
Orange, California, 92868
Circuit Clinical
Orchard Park, New York, 14127
Univ of Pennsylvania Medical Center
Philadelphia, Pennsylvania, 19104
School Of Medicine
Sacromento, California, 95817
Uni of Texas Health Science Center
San Antonio, Texas, 78229
University of California San Diego
San Deigo, California, 92037
Kaiser Permanente
San Diego, California, 92111
Brazil9 sites
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-221
Novartis Investigative Site
Juiz de Fora, Minas Gerais, 36010-570
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90035-003
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90035-074
Novartis Investigative Site
Recife, Pernambuco, 50740-900
Novartis Investigative Site
Salvador, Estado de Bahia, 40150-150
Novartis Investigative Site
Salvador, 40323-010
Novartis Investigative Site
Santo André, São Paulo, 09090-790
Novartis Investigative Site
Vitória, Espírito Santo, 29055-450
Spain9 sites
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Madrid, 28027
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320
Novartis Investigative Site
Santiago Compostela, A Coruna, 15706
Novartis Investigative Site
Valencia, Valencia, 46017
Novartis Investigative Site
Vigo, Pontevedra, 36214
France8 sites
Novartis Investigative Site
Besançon, 25030
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Grenoble, 38043
Novartis Investigative Site
Lyon, 69003
Novartis Investigative Site
Marseille, 13005
Novartis Investigative Site
Poitiers, 86021
Novartis Investigative Site
Toulouse, 31054
Novartis Investigative Site
Vandœuvre-lès-Nancy, 54511
Canada7 sites
Novartis Investigative Site
Calgary, Alberta, T2N 4Z6
Novartis Investigative Site
Etobicoke, Ontario, M9W 6V1
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Sherbrooke, Quebec, J1G 2E8
Novartis Investigative Site
Toronto, Ontario, M5T 2S8
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1L7
Novartis Investigative Site
Winnipeg, Manitoba, R3A 1R9
South Korea7 sites
Novartis Investigative Site
Gwangju, 61469
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 04763
Novartis Investigative Site
Seoul, 05505
Novartis Investigative Site
Seoul, 06591
Novartis Investigative Site
Seoul
Novartis Investigative Site
Suwon, Gyeonggi-do, 16499
Argentina5 sites
Novartis Investigative Site
Caba, C1015ABO
Novartis Investigative Site
CABA, Buenos Aires, C1056ABI
Novartis Investigative Site
CABA, C1426ABP
Novartis Investigative Site
La Plata, Buenos Aires, B1900AWT
Novartis Investigative Site
San Miguel de Tucumán, T4000AXL
Thailand5 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Novartis Investigative Site
Chiang Mai, 50200
Novartis Investigative Site
Songkhla, Hat Yai, 90110
India4 sites
Novartis Investigative Site
Bangalore, Karnataka, 560079
Novartis Investigative Site
Chandigarh, 160012
Novartis Investigative Site
Lucknow, Uttar Pradesh, 226014
Novartis Investigative Site
Secunderabad, Telangana, 500003
Mexico4 sites
Novartis Investigative Site
León, Guanajuato, 37160
Novartis Investigative Site
Monterrey, Nuevo León, 64440
Novartis Investigative Site
Oaxaca City, 68020
Novartis Investigative Site
Querétaro, 76070
Taiwan4 sites
Novartis Investigative Site
Kaohsiung City, 833
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taichung, 407219
Novartis Investigative Site
Taipei, 11217
Colombia3 sites
Novartis Investigative Site
Barranquilla, Atlántico, 080020
Novartis Investigative Site
Bogota, Cundinamarca, 110111
Novartis Investigative Site
Medellín, Antioquia, 050001
Guatemala3 sites
Novartis Investigative Site
Guatemala City, Departamento de Guatemala, 01011
Novartis Investigative Site
Guatemala City, 01010
Novartis Investigative Site
Quetzaltenango, Departamento de Quetzaltenango, 09001
Malaysia3 sites
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Novartis Investigative Site
Kuala Terengganu, Terengganu, 20400
Novartis Investigative Site
Sibu, Sarawak, 96000
Romania3 sites
Novartis Investigative Site
Bucharest, 022328
Novartis Investigative Site
Oradea, Jud Bihor, 410619
Novartis Investigative Site
Timișoara, Timiș County, 300723
Chile2 sites
Novartis Investigative Site
Santiago, RM, 7500922
Novartis Investigative Site
Temuco, 4781151
Czechia2 sites
Novartis Investigative Site
Olomouc, 779 00
Novartis Investigative Site
Prague, 128 00
Germany2 sites
Novartis Investigative Site
Aachen, 52074
Novartis Investigative Site
Bochum, 44791
Hungary2 sites
Novartis Investigative Site
Budapest, 1097
Novartis Investigative Site
Debrecen, Hajdu Bihar Megye, 4032
Italy2 sites
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Udine, UD, 33100
Lithuania2 sites
Novartis Investigative Site
Kaunas, LTU, LT-50161
Novartis Investigative Site
Vilnius, LT-08406
Singapore2 sites
Novartis Investigative Site
Singapore, Singapore, 308433
Novartis Investigative Site
Singapore, 169608
United Kingdom2 sites
Novartis Investigative Site
Bradford, West Yorkshire, BD9 6RJ
Novartis Investigative Site
London, SE1 9RT
Vietnam2 sites
Novartis Investigative Site
Hanoi, 100000
Novartis Investigative Site
Ho Chi Minh City, 700000
About this study
Official title: A Randomized, Double-blind, Parallel Group, Placebo-controlled, Multicenter Phase 3 Trial to Evaluate Efficacy, Safety and Tolerability of Ianalumab on Top of Standard-of-care Therapy in Participants With Active Lupus Nephritis (SIRIUS-LN).
This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN
Read the detailed description
This trial will evaluate the efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or ianalumab given every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous). using the 2003 International Society for Nephrology (ISN)/Renal Pathology Society (RPS) criteria).
- Conditions
- Lupus Nephritis
- Being tested
- ianalumab s.c. q4w, ianalumab s.c. q12w, placebo s.c.
- Keywords
- SLE, Systemic Lupus Erythematosus (SLE), Kidney inflammation, Anti-BAFF-receptor, B cell depletion, Ianalumab, VAY736
- Medical subject headings
- Lupus Nephritis, Lupus Erythematosus, Systemic, Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ianalumab s.c. q4wDrug
Also called VAY736
ianalumab s.c. q4w in addition to SoC
ianalumab s.c. q12wDrug
Also called VAY736
ianalumab s.c. q12w in addition to SoC
placebo s.c.Drug
Also called placebo
placebo s.c. q4w in addition to SoC
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - ianalumab s.c. q4w | Experimental | ianalumab s.c. q4w in addition to standard of care (SoC) Receives: Drug: ianalumab s.c. q4w |
| Arm 2 - ianalumab s.c. q12w | Experimental | ianalumab s.c. q12w in addition to SoC Receives: Drug: ianalumab s.c. q12w |
| Arm 3 - placebo s.c. q4w | Placebo comparator | Placebo s.c. q4w in addition to SoC Receives: Drug: placebo s.c. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and percentage of participants achieving stable Complete Renal Response (CRR)
The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 or no less than 85% of baseline, AND, 24-hour UPCR <0.5 g/g) at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy.
Measured: Week 72
Secondary outcomes (9)
Time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or ≥50% reduction from baseline
To demonstrate superiority of ianalumab, compared to placebo, in time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or ≥50% reduction from baseline up to Week 72
Measured: Week 72
Percentage of participants achieving stable Overall Renal Response (ORR), defined as achievement as either Complete Renal Response (CRR) or Partial Renal Response (PRR)
To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Overall Renal Response (ORR) at Week 48
Measured: Week 48
Incidence of stable Complete Renal Response (CRR) while maintaining daily corticosteroid dose ≤5 mg/day
To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Complete Renal Response (CRR) at Week 72 while maintaining daily corticosteroid dose ≤5 mg/day between Week 24 and Week 72
Measured: Week 72
Incidence of renal-related event or death
To demonstrate superiority of ianalumab, compared to placebo, in preventing renal-related event or death through Week 72
Measured: Week 72
Change in British Isles Lupus Activity Group (BILAG) score
To demonstrate superiority of ianalumab, compared to placebo in BILAG-2004 at Week 72
Measured: Week 72
Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score
To demonstrate superiority of ianalumab, compared to placebo, in FACIT-Fatigue at Week 72
Measured: Week 72
Number of participants with treatment-emergent Adverse Events (AEs)
AEs are any untoward sign or symptom that occurs during the study treatment
Measured: Week 72
Ianalumab concentration in serum
To characterize the pharmacokinetics (PK) of ianalumab mean, median, minimum and maximum concentrations will be provided
Measured: Week 72
Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time
To evaluate immunogenicity of ianalumab
Measured: Week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2021
- Study start14 Jul 2022
- Primary completion21 Sep 2027 (estimated)
- Study completion4 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus NephritisStudies 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
- This is a pivotal double-blind, randomized, placebo-controlled, multi-center three-arm study, evaluating at Week 72 efficacy and safety of ianalumab administered s.c. every 4 weeks or ianalumab administered s.c. every 12 weeks versus placebo, administered s.c. every 4 weeks, in adult participants with active LN receiving SoC. In addition, long-term efficacy, safety and tolerability will be collected up to Week 144.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 452 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
- NCT05126277
- Sponsor's protocol ID
- CVAY736K12301
- Other IDs
- 2020-005830-14, 2023-508559-37-00, 2023
- Acronym
- SIRIUS-LN
- Status last verified
- Oct 2026
- First submitted
- 15 Oct 2021
- Last updated
- 15 Oct 2026
- Results posted
- No
- 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