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: November 13, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Systemic Lupus Erythematosus	Drug: ianalumab; Drug: placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 21, 2023
• Estimated Primary Completion Date: January 26, 2027
• Estimated Study Completion Date: January 23, 2029

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. Proportion of participants with Adverse Events (AEs) [ Time Frame: Baseline to Week 60 ]
   To evaluate safety and tolerability of ianalumab s.c. monthly
10. 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
11. Ianalumab concentration in serum during the treatment and follow-up [ Time Frame: Baseline to Week 164 ]
    Concentration of Ianalumab in serum

Eligibility Criteria

• 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 according to 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).
• Active viral, bacterial or other infections requiring systemic treatment at the time of screening or randomization or history of recurrent 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 exceeding protocol-defined limits prior to randomization
• 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

Contacts

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

Contact: Novartis Pharmaceuticals; +41613241111

Locations

United States, Alabama

Novartis Investigative Site; Recruiting

Anniston, Alabama, United States, 36207-5710

United States, California

Novartis Investigative Site; Recruiting

La Palma, California, United States, 90623

United States, Kentucky

Novartis Investigative Site; Recruiting

Lexington, Kentucky, United States, 40504

United States, Louisiana

Novartis Investigative Site; Recruiting

Lake Charles, Louisiana, United States, 70601

United States, Michigan

Novartis Investigative Site; Recruiting

Grand Blanc, Michigan, United States, 48439

United States, Tennessee

Novartis Investigative Site; Recruiting

Jackson, Tennessee, United States, 38305

United States, Texas

Novartis Investigative Site; Recruiting

Bellaire, Texas, United States, 77401

Argentina

Novartis Investigative Site; Recruiting

Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1015ABO

Novartis Investigative Site; Recruiting

San Miguel, Buenos Aires, Argentina, 1663

Novartis Investigative Site; Recruiting

San Miguel de Tucuman, Tucuman, Argentina, T4000CBC

Novartis Investigative Site; Recruiting

Tucuman, Argentina, 4000

Australia, New South Wales

Novartis Investigative Site; Recruiting

St Leonards, New South Wales, Australia, 2065

Australia, Queensland

Novartis Investigative Site; Recruiting

Maroochydore, Queensland, Australia, 4558

France

Novartis Investigative Site; Recruiting

Angers Cedex 9, France, 49933

Novartis Investigative Site; Recruiting

Grenoble, France, 38043

Novartis Investigative Site; Recruiting

Montpellier Cedex 5, France, 34295

Novartis Investigative Site; Recruiting

Paris 13, France, 75651

Novartis Investigative Site; Recruiting

Paris, France, 75014

Novartis Investigative Site; Recruiting

Tours, France, 37044

Germany

Novartis Investigative Site; Recruiting

Berlin, Germany, 13353

Novartis Investigative Site; Recruiting

Freiburg, Germany, 79106

Novartis Investigative Site; Recruiting

Herne, Germany, 44649

Novartis Investigative Site; Recruiting

Koeln, Germany, 50937

Novartis Investigative Site; Recruiting

Leipzig, Germany, 04103

Novartis Investigative Site; Recruiting

Mainz, Germany, 55131

Italy

Novartis Investigative Site; Recruiting

Ancona, AN, Italy, 60020

Novartis Investigative Site; Recruiting

Pisa, PI, Italy, 56126

Novartis Investigative Site; Recruiting

Torino, TO, Italy, 10128

Novartis Investigative Site; Recruiting

Milano, Italy, 20126

Korea, Republic of

Novartis Investigative Site; Recruiting

Daejeon, Korea, Korea, Republic of, 35015

Novartis Investigative Site; Recruiting

Seoul, Seocho Gu, Korea, Republic of, 06591

Novartis Investigative Site; Recruiting

Seoul, Korea, Republic of, 04763

Malaysia

Novartis Investigative Site; Recruiting

Ipoh, Perak, Malaysia, 30450

Novartis Investigative Site; Recruiting

Kuching, Sarawak, Malaysia, 93586

Novartis Investigative Site; Recruiting

Selangor Darul Ehsan, Malaysia, 68100

Romania

Novartis Investigative Site; Recruiting

Brasov, Romania, 500283

Novartis Investigative Site; Recruiting

Bucuresti, Romania, 011172

Novartis Investigative Site; Recruiting

Cluj-Napoca, Romania, 400006

Taiwan

Novartis Investigative Site; Recruiting

Kaohsiung, Taiwan, 83301

Novartis Investigative Site; Recruiting

Taichung, Taiwan, 40447

Novartis Investigative Site; Recruiting

Taichung, Taiwan, 40705

Novartis Investigative Site; Recruiting

Taipei, Taiwan, 11217

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05624749
• Other Study ID Numbers: CVAY736F12302; 2022-002690-29 ( EudraCT Number )
• First Posted: November 22, 2022
• Last Update Posted: November 13, 2023
• Last Verified: November 2023

Individual Participant Data (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

• 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:

Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases