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)
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| ClinicalTrials.gov Identifier: NCT05639114 |
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Recruitment Status :
Recruiting
First Posted : December 6, 2022
Last Update Posted : November 13, 2023
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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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 |
| 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 Genetics related topics:
Systemic lupus erythematosus
MedlinePlus related topics:
Lupus
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ianalumab s.c. monthly
Ianalumab s.c. monthly
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Drug: Ianalumab
ianalumab s.c. monthly or quarterly
Other Name: VAY736 |
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Experimental: Ianalumab s.c. quarterly
Ianalumab s.c. quarterly
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Drug: Ianalumab
ianalumab s.c. monthly or quarterly
Other Name: VAY736 |
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Placebo Comparator: Placebo s.c. monthly
placebo s.c. monthly
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Drug: Placebo
placebo s.c. monthly |
Primary Outcome Measures :
- 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 :
- 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)
- 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
- 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
- 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
- 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
- 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
- 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
- Proportion of participants on monthly or quarterly ianalumab maintaining between Week 24 and Week 60 a reduced corticosteroid 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 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
- 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
- Number of participants with adverse events [ Time Frame: Baseline to Week 60 ]To evaluate safety and tolerability of ianalumab s.c. monthly or quarterly
- 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
- Ianalumab concentration in serum during the treatment and follow-up [ Time Frame: Baseline to week 164 ]Ianalumab concentration in serum
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| 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"
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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
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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
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
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
| Contact: Novartis Pharmaceuticals | +41613241111 |
Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT05639114 |
| Other Study ID Numbers: |
CVAY736F12301 2022-002691-36 ( EudraCT Number ) |
| First Posted: | December 6, 2022 Key Record Dates |
| 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 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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Systemic Lupus Erythematosus SLE B cell depletion SLEDAI-2K |
BILAG-2004 SRI ANA |
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |