Phase 3 study to evaluate ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

17 May 2023 → ongoing

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508499-12-00

EudraCT number

2022-002690-29

ClinicalTrials.gov

NCT05624749

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacodynamic, Others, Pharmacokinetic, Safety, Pharmacogenetic

To demonstrate superiority of xxx ianalumab XXX mg xxx XXX, compared to placebo, in achieving Systemic Lupus Erythematosus Responder Index (SRI-4) at Week 60

Secondary objectives 4

1. To demonstrate superiority of xxx ianalumab xxx mg xxx compared to placebo in: - Reducing moderate or severe British Isles Lupus Assessment Group flares up to Week(Wk) 60; - Maintaining corticosteroiddose ≤5 mg/day or ≤baseline dose, whichever is lower, b/w Wk 36 & Wk 60; - Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment at Wk 60; - Achieving Lupus Low Disease Activity State at Wk 60; - Time to first occurrence of SRI-4 from baseline up to Wk 60; - Achieving SRI-4 at Wk 60 while maintaining reduced corticosteroid dose ≤5 mg/day or ≤baseline dose, whichever is lower, b/w Wk 36 & Wk 60; - Achieving SRI-6 at Wk 60; - Achieving Short form 36 (SF-26) Bodily Pain response at Week 60
2. To evaluate safety & tolerability of ianalumab xxx mg xxx XXX
3. To evaluate immunogenicity of ianalumab xxx mg xxx XXX
4. To characterize the PK of ianalumab XXX mg xxx XXX

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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.
2. Diagnosis of systemic lupus erythematosus (SLE) meeting the EULAR/ACR SLE classification criteria at least 6 months prior to screening
3. Elevated serum titers at screening of Antinuclear Antibodies (≥1:80) as determined by a central laboratory with a SLE typical fluorescence pattern.
4. Currently receiving corticosteroids and/or anti-malarial treatment and/or another Disease-modifying antirheumatic drug (DMARD) as specified in the protocol.
5. SLEDAI-2K Criteria at screening: SLEDAI-2K score ≥6 points, excluding points attributed to "fever", "lupus headache", "alopecia", and "organic brain syndrome" British Isles Lupus Assessment Group-2004 disease activity level at screening of at least 1 of the following: British Isles Lupus Assessment Group-2004 level A disease in ≥1 organ system, Or British Isles Lupus Assessment Group-2004 level B disease in ≥2 organ systems
6. Weigh at least 35 kg at screening

Exclusion criteria 16

1. Prior treatment with Ianalumab
2. Chronic infection with hepatitis B (HBV) or hepatitis C (HCV)
3. Evidence of active tuberculosis infection
4. History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result at screening
5. Any one of the following 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 anemia Absolute neutrophil count (ANC) (<0.8 x 10^3/ μL)
6. Severe organ dysfunction or life-threatening disease at screening
7. Presence of severe lupus kidney disease as defined by proteinuria above 2g/day or equivalent using spot urine protein creatinine ratio
8. XXX
9. Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study
10. Receipt of live/attenuated vaccine within a 4-week period before first dosing
11. 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
12. Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or chronic treatment with systemic CS
13. History of malignancy of any organ system other than localized basal cell carcinoma of the skin or in situ cervical cancer
14. Pregnant or nursing (lactating) women.
15. History of receiving following treatment I) high dose corticosteroids, calcineurin inhibitors, JAK or other kinase inhibitors or other DMARD (except as listed in inclusion criteria) 12 weeks prior to screening II) Cyclophosphamide or biologics such as immunoglobulins (i.v. or XXX), plasmapheresis, anti-type I interferon receptor biologic agents, anti- CD40 agents, CTLA4-Fc Ig or B-cell activating factor-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
16. Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving SRI-4 at Week 60

Secondary endpoints 13

1. Proportion of participants with no moderate or severe British Isles Lupus Assessment Group flare up to Week 60
2. Proportion of participants maintaining between Week 36 and Week 60 a reduced corticosteroid dose of predniso(lo)ne ≤5 mg/day or ≤baseline dose, whichever is lower
3. Proportion of participants achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment at Week 60
4. Proportion of participants achieving Lupus Low Disease Activity State at Week 60
5. 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 corticosteroid dose of predniso(lo)ne ≤5 mg/day or ≤baseline dose, whichever is lower
7. Proportion of participants achieving SRI-6 at Week 60
8. Proportion of participants achieving SF-36 Bodily Pain response at Week 60
9. Proportion of participants with AEs and SAEs
10. Clinical laboratory measurements
11. Vital Signs
12. Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time
13. Ianalumab concentration in serum during the treatment and followup (up to the end of study)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 13

Locations

4 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications