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

April 11, 2024 updated by: Novartis Pharmaceuticals

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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)

Study Type

Interventional

Enrollment (Estimated)

280

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Argentina
      • Tucuman, Argentina, 4000
        • Recruiting
        • Novartis Investigative Site
    • Buenos Aires
      • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO
        • Recruiting
        • Novartis Investigative Site
      • San Miguel, Buenos Aires, Argentina, 1663
        • Recruiting
        • Novartis Investigative Site
    • Tucuman
      • San Miguel de Tucuman, Tucuman, Argentina, T4000CBC
        • Recruiting
        • Novartis Investigative Site
  • Australia
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • Recruiting
        • Novartis Investigative Site
    • Queensland
      • Maroochydore, Queensland, Australia, 4558
        • Recruiting
        • Novartis Investigative Site
    • Western Australia
      • Victoria Park, Western Australia, Australia, 6100
        • Withdrawn
        • Novartis Investigative Site
  • Chile
      • Concepcion, Chile, 6740
        • Recruiting
        • Novartis Investigative Site
      • Santiago, Chile, 7500710
        • Recruiting
        • Novartis Investigative Site
    • Los Rios
      • Valdivia, Los Rios, Chile, 5110683
        • Recruiting
        • Novartis Investigative Site
    • RM
      • Santiago, RM, Chile, 7500588
        • Recruiting
        • Novartis Investigative Site
  • Colombia
      • Barranquilla, Colombia, 080020
        • Recruiting
        • Novartis Investigative Site
      • Bogota, Colombia, 111611
        • Recruiting
        • Novartis Investigative Site
      • Cundinamarca, Colombia, 111121
        • Recruiting
        • Novartis Investigative Site
    • Antioquia
      • Medellin, Antioquia, Colombia, 050001
        • Recruiting
        • Novartis Investigative Site
    • Atlantico
      • Barranquilla, Atlantico, Colombia, 080002
        • Recruiting
        • Novartis Investigative Site
    • Santander
      • Bucaramanga, Santander, Colombia, 0001
        • Recruiting
        • Novartis Investigative Site
  • France
      • Angers Cedex 9, France, 49933
        • Recruiting
        • Novartis Investigative Site
      • Grenoble, France, 38043
        • Recruiting
        • Novartis Investigative Site
      • Montpellier Cedex 5, France, 34295
        • Recruiting
        • Novartis Investigative Site
      • Paris, France, 75018
        • Recruiting
        • Novartis Investigative Site
      • Paris, France, 75014
        • Recruiting
        • Novartis Investigative Site
      • Paris 13, France, 75651
        • Recruiting
        • Novartis Investigative Site
      • Toulouse, France, 31400
        • Recruiting
        • Novartis Investigative Site
      • Toulouse 4, France, 31054
        • Recruiting
        • Novartis Investigative Site
      • Tours, France, 37044
        • Recruiting
        • Novartis Investigative Site
  • Germany
      • Aachen, Germany, 52074
        • Recruiting
        • Novartis Investigative Site
      • Berlin, Germany, 13353
        • Recruiting
        • Novartis Investigative Site
      • Erlangen, Germany, 91056
        • Recruiting
        • Novartis Investigative Site
      • Freiburg, Germany, 79106
        • Recruiting
        • Novartis Investigative Site
      • Herne, Germany, 44649
        • Recruiting
        • Novartis Investigative Site
      • Koeln, Germany, 50937
        • Recruiting
        • Novartis Investigative Site
      • Leipzig, Germany, 04103
        • Recruiting
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Recruiting
        • Novartis Investigative Site
  • India
      • Visakhapatnam, India, 530040
        • Recruiting
        • Novartis Investigative Site
    • Gujarat
      • Ahmedabad, Gujarat, India, 380006
        • Recruiting
        • Novartis Investigative Site
    • Kerala
      • Kozhikode, Kerala, India, 673008
        • Recruiting
        • Novartis Investigative Site
    • Maharashtra
      • Nagpur, Maharashtra, India, 441108
        • Recruiting
        • Novartis Investigative Site
      • Pune, Maharashtra, India, 411001
        • Recruiting
        • Novartis Investigative Site
    • Telangana
      • Secunderabad, Telangana, India, 500003
        • Recruiting
        • Novartis Investigative Site
  • Italy
      • Milano, Italy, 20126
        • Recruiting
        • Novartis Investigative Site
    • AN
      • Ancona, AN, Italy, 60020
        • Recruiting
        • Novartis Investigative Site
    • FE
      • Cona, FE, Italy, 44100
        • Recruiting
        • Novartis Investigative Site
    • PD
      • Padova, PD, Italy, 35128
        • Recruiting
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56126
        • Recruiting
        • Novartis Investigative Site
    • TO
      • Torino, TO, Italy, 10128
        • Recruiting
        • Novartis Investigative Site
  • Korea, Republic of
      • Gwangju Gwangyeoksi, Korea, Republic of, 61748
        • Recruiting
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 04763
        • Recruiting
        • Novartis Investigative Site
    • Korea
      • Daejeon, Korea, Korea, Republic of, 35015
        • Recruiting
        • Novartis Investigative Site
    • Seocho Gu
      • Seoul, Seocho Gu, Korea, Republic of, 06591
        • Recruiting
        • Novartis Investigative Site
  • Malaysia
      • Selangor Darul Ehsan, Malaysia, 68100
        • Recruiting
        • Novartis Investigative Site
    • Negeri Sembilan
      • Seremban, Negeri Sembilan, Malaysia, 70300
        • Recruiting
        • Novartis Investigative Site
    • Perak
      • Ipoh, Perak, Malaysia, 30450
        • Recruiting
        • Novartis Investigative Site
    • Sarawak
      • Kuching, Sarawak, Malaysia, 93586
        • Recruiting
        • Novartis Investigative Site
  • Mexico
      • Mexico, Mexico, 07760
        • Recruiting
        • Novartis Investigative Site
    • Guanajuato
      • Leon, Guanajuato, Mexico, 37160
        • Recruiting
        • Novartis Investigative Site
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44160
        • Recruiting
        • Novartis Investigative Site
    • Yucatan
      • Merida, Yucatan, Mexico, 97070
        • Recruiting
        • Novartis Investigative Site
  • Romania
      • Brasov, Romania, 500283
        • Recruiting
        • Novartis Investigative Site
      • Bucuresti, Romania, 011172
        • Recruiting
        • Novartis Investigative Site
      • Cluj-Napoca, Romania, 400006
        • Recruiting
        • Novartis Investigative Site
  • Taiwan
      • Kaohsiung, Taiwan, 83301
        • Recruiting
        • Novartis Investigative Site
      • Taichung, Taiwan, 40447
        • Recruiting
        • Novartis Investigative Site
      • Taichung, Taiwan, 40705
        • Recruiting
        • Novartis Investigative Site
      • Taipei, Taiwan, 11217
        • Recruiting
        • Novartis Investigative Site
      • Taoyuan, Taiwan, 33305
        • Recruiting
        • Novartis Investigative Site
  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207-5710
        • Recruiting
        • Pinnacle Research Group LLC .
        • Contact:
        • Principal Investigator:
          • Vishala L. Chindalore
    • California
      • Irvine, California, United States, 92660
        • Recruiting
        • University of Calif Irvine Med Cntr
        • Contact:
        • Principal Investigator:
          • Sheetal Desai
      • La Palma, California, United States, 90623
        • Recruiting
        • Advanced Medical Research
        • Contact:
        • Principal Investigator:
          • Gerald Ho
    • Florida
      • Miami, Florida, United States, 33032
        • Recruiting
        • Homestead Associates in Research Inc
        • Principal Investigator:
          • Gilberto Seco
        • Contact:
      • Plantation, Florida, United States, 33324
        • Recruiting
        • Integral Rheumatology and Immunology Specialists IRIS
        • Principal Investigator:
          • Guillermo Valenzuela
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • Recruiting
        • Bluegrass Community Research Inc
        • Contact:
        • Principal Investigator:
          • Alexander Brown
    • Louisiana
      • Lake Charles, Louisiana, United States, 70601
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University Of Maryland Rheumatology
        • Contact:
        • Principal Investigator:
          • Violeta Rus
    • Michigan
      • Grand Blanc, Michigan, United States, 48439
        • Recruiting
        • Ahmed Arif Medical Research Center
        • Principal Investigator:
          • Ali Karrar
        • Contact:
          • Phone Number: 810-953-8700
    • Tennessee
      • Jackson, Tennessee, United States, 38305
        • Recruiting
        • West Tennessee Research Institute
        • Contact:
          • Phone Number: 731-664-7824
        • Principal Investigator:
          • Jacob A. Aelion
    • Texas
      • Bellaire, Texas, United States, 77401
        • Recruiting
        • Novel Research LLC
        • Contact:
        • Principal Investigator:
          • Wajeeha Yousaf

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ianalumab s.c. monthly
Drug: ianalumab
ianalumab s.c. monthly
Other Names:
  • VAY736
Placebo Comparator: placebo s.c. monthly
Drug: placebo
placebo s.c. monthly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants achieving Systemic Lupus Erythematosus Responder Index -4 (SRI-4)
Time Frame: Week 60

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants with no moderate or severe BILAG flare
Time Frame: Baseline to Week 60
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
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
Time Frame: Week 36 to Week 60
Maintaining reduced CS dose from Week 36 to Week 60
Week 36 to Week 60
Proportion of participants achieving BILAG-based Composite Lupus Assessment (BICLA)
Time Frame: Week 60

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
Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)
Time Frame: Week 60

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
Time to first occurrence of SRI-4
Time Frame: Baseline to Week 60
Time to first occurrence of SRI-4 from baseline to Week 60
Baseline to Week 60
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
Time Frame: Week 36 to Week 60
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
Proportion of participants achieving SRI-6
Time Frame: Week 60

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
Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time
Time Frame: Baseline to Week 164
To evaluate immunogenicity of ianalumab s.c. monthly
Baseline to Week 164
Ianalumab concentration in serum during the treatment and follow-up
Time Frame: Baseline to Week 164
Concentration of Ianalumab in serum
Baseline to Week 164
Proportion of participants with Adverse Events (AEs)
Time Frame: Baseline to Week 60
To evaluate safety and tolerability of ianalumab s.c. monthly
Baseline to Week 60
Proportion of participants achieving SF-36 Bodily Pain response
Time Frame: Week 60
Achieving Short Form 36 (SF-36) Bodily Pain response
Week 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 21, 2023

Primary Completion (Estimated)

January 26, 2027

Study Completion (Estimated)

January 23, 2029

Study Registration Dates

First Submitted

November 7, 2022

First Submitted That Met QC Criteria

November 21, 2022

First Posted (Actual)

November 22, 2022

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CVAY736F12302
  • 2022-002690-29 (EudraCT Number)
  • 2023-508499-12-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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