Phase 3 study to evaluate two regimens of ianalumab on top of standardof- care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 1)

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

3 Feb 2023 → ongoing

Decision date (initial)

2024-08-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508498-97-00

EudraCT number

2022-002691-36

ClinicalTrials.gov

NCT05639114

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

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

The primary clinical question of interest is: 

What is the effect of s.c. ianalumab XXX mg XXX regimen compared to placebo on top of standard-of-care on achieving SRI-4 at Week 60 without treatment discontinuation or use of restricted/rescue medications, in adult and adolescent participants diagnosed with anti-nuclear antibodies-positive systemic lupus erythematosus of moderate-to-severe disease activity?

Secondary objectives 5

1. To demonstrate superiority of s.c. ianalumab XXX mg XXX compared to placebo in: • Reducing moderate or severe British Isles Lupus Assessment Group (BILAG)-2004 flares up to Week 60 • Maintaining corticosteroid (CS) dose ≤ 5 mg/day or ≤ baseline dose, whichever is lower, between Week 36 and Week 60 • Achieving BILAG-based Composite Lupus Assessment (BICLA) at Week 60 • Achieving Lupus Low Disease Activity State (LLDAS) at Week 60 • Time to first occurrence of SRI-4 from baseline up to Week 60 • Achieving SRI-4 at Week 60 while maintaining reduced CS dose ≤ 5 mg/day or ≤ baseline dose, whichever is lower, between Week 36 and Week 60 • Achieving SRI-6 at Week 60 • Achieving Short Form 36 (SF-36) Bodily Pain response at Week 60
2. To demonstrate superiority of s.c. ianalumab XXX mg XXX compared to placebo for SRI-4 and the secondary objectives listed above
3. To evaluate safety and tolerability of ianalumab XXX mg s.c. (XXX or XXX)
4. To evaluate immunogenicity of ianalumab XXX mg s.c. (XXX or XXX)
5. To characterize the pharmacokinetics of ianalumab XXX mg s.c. (XXX or XXX)

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD 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

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 meeting the 2019 European League Against Rheumatism/American College of Rheumatology (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 17

1. Prior treatment with ianalumab
2. Receipt of live/attenuated vaccine within a 4-week period before first dosing
3. 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
4. Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or chronic treatment with systemic CS
5. History of malignancy of any organ system other than localized basal cell carcinoma of the skin or in situ cervical cancer
6. Pregnant or nursing (lactating) women.
7. 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 s.c.), 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
8. Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection
9. Chronic infection with hepatitis B (HBV) or hepatitis C (HCV)
10. Evidence of active tuberculosis infection
11. History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result at screening
12. 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)
13. Severe organ dysfunction or life-threatening disease at screening
14. Presence of severe lupus kidney disease as defined by proteinuria above 2g/day or equivalent using spot urine protein creatinine ratio
15. XXX
16. XXX
17. Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study

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 9

Locations

7 EU/EEA countries · 46 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 86 files

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

Application history

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