This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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) (SIRIUS-SLE 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05639114
Recruitment Status : Recruiting
First Posted : December 6, 2022
Last Update Posted : April 3, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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).

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: Ianalumab Drug: Placebo Phase 3

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)
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 406 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 2, 2023
Estimated Primary Completion Date : January 19, 2027
Estimated Study Completion Date : January 16, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Ianalumab s.c. monthly
Ianalumab s.c. monthly
 Drug: Ianalumab
ianalumab s.c. monthly or quarterly
Other Name: VAY736
Experimental: Ianalumab s.c. quarterly
Ianalumab s.c. quarterly
 Drug: Ianalumab
ianalumab s.c. monthly or quarterly
Other Name: VAY736
Placebo Comparator: Placebo s.c. monthly
placebo s.c. monthly
 Drug: Placebo
placebo s.c. monthly


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Proportion of participants on monthly ianalumab 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


Secondary Outcome Measures :
  1. Proportion of participants on monthly or quarterly ianalumab with no moderate or severe British Isles Lupus Assessment Group (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)

  2. 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 [ Time Frame: Week 36 to Week 60 ]
    Maintaining reduced CS dose from Week 36 to Week 60

  3. Proportion of participants on monthly or quarterly ianalumab 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

  4. Proportion of participants on monthly or quarterly ianalumab 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).
    • 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

  5. Time to first occurrence of SRI-4 (participants on ianalumab monthly or quarterly) [ Time Frame: Baseline to Week 60 ]
    Time to first occurrence of SRI-4 from baseline to Week 60

  6. 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 [ 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

  7. Proportion of participants on monthly or quarterly ianalumab 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

  8. Proportion of participants on monthly or quarterly ianalumab achieving Short Form 36 (SF-36) Bodily Pain response [ Time Frame: Week 60 ]
    Achieving SF-36 Bodily Pain response

  9. Proportion of participants on quarterly ianalumab achieving SRI-4 [ Time Frame: Week 60 ]

    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

  10. Proportion of participants on monthly or quarterly ianalumab with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline to Week 60 ]
    To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly

  11. Number of participants with adverse events [ Time Frame: Baseline to Week 60 ]
    To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly

  12. Proportion of participants with anti-ianalumab antibodies in serum (ADA assay) over time [ Time Frame: Baseline to Week 164 ]
    Immunogenicity of ianalumab s.c. monthly or quarterly

  13. Ianalumab concentration in serum during the treatment and follow-up [ Time Frame: Baseline to week 164 ]
    Ianalumab concentration in serum


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05639114


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
Show Show 122 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05639114    
Other Study ID Numbers: CVAY736F12301
2022-002691-36 ( EudraCT Number )
2023-508498-97 ( Other Identifier: EU CT number )
First Posted: December 6, 2022    Key Record Dates
Last Update Posted: April 3, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Systemic Lupus Erythematosus
SLE
B cell depletion
SLEDAI-2K
 BILAG-2004
SRI
ANA
Additional relevant MeSH terms:
Layout table for MeSH terms
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases