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)

• ClinicalTrials.gov Identifier: NCT05624749
• Recruitment Status: Recruiting
• First Posted: November 22, 2022
• Last Update Posted: May 7, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: November 7, 2022
• First Posted Date: November 22, 2022
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: April 21, 2023
• Estimated Primary Completion Date: January 26, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 11, 2023)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Proportion of participants achieving SF-36 Bodily Pain response [ Time Frame: Week 60 ]
  Achieving Short Form 36 (SF-36) Bodily Pain response
• Proportion of participants with Adverse Events (AEs) [ Time Frame: Baseline to Week 60 ]
  To evaluate safety and tolerability of ianalumab s.c. monthly
• 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
• Ianalumab concentration in serum during the treatment and follow-up [ Time Frame: Baseline to Week 164 ]
  Concentration of Ianalumab in serum

Original Secondary Outcome Measures (submitted: November 21, 2022)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• Proportion of participants maintaining between Week 24 and Week 60 a reduced CS dose of predniso(lo)ne ≤ 5 mg/day, or ≤ baseline dose, whichever is lower [ Time Frame: Week 24 to Week 60 ]
  Maintaining CS dose ≤ 5 mg/day or ≤baseline dose, whichever is lower, between Week 24 and Week 60
• Proportion of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Clinical laboratory measurements, Vital signs [ Time Frame: Baseline to Week 60 ]
  To evaluate safety and tolerability of ianalumab s.c. monthly
• 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
• Ianalumab concentration in serum during the treatment and follow-up [ Time Frame: Baseline to Week 164 ]
  Concentration of Ianalumab in serum

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)
• Official Title: 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)
• Brief Summary: 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).
• 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Drug: ianalumab
  ianalumab s.c. monthly
  Other Name: VAY736
• Drug: placebo
  placebo s.c. monthly

Study Arms

• Experimental: ianalumab s.c. monthly
  ianalumab s.c. monthly
  Intervention: Drug: ianalumab
• Placebo Comparator: placebo s.c. monthly
  placebo s.c. monthly
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 21, 2022): 280
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 23, 2029
• Estimated Primary Completion Date: January 26, 2027 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Argentina, Australia, Chile, Colombia, France, Germany, India, Italy, Korea, Republic of, Malaysia, Mexico, Romania, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05624749
• Other Study ID Numbers: CVAY736F12302; 2022-002690-29 ( EudraCT Number ); 2023-508499-12-00 ( Other Identifier: EU CT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: May 2024