| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Systemic Lupus Erythematosus | |
| E.1.1.1 | Medical condition in easily understood language | | An inflammatory disease caused when the immune system attacks its own tissues. | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10042945 | | E.1.2 | Term | Systemic lupus erythematosus | | E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To demonstrate superiority of subcutaneous (s.c.) ianalumab 300 mg monthly, compared to placebo, in achieving Systemic Lupus Erythematosus Responder Index (SRI-4) at Week 60 | |
| E.2.2 | Secondary objectives of the trial | To demonstrate superiority of s.c. ianalumab 300 mg monthly compared to placebo in: Reducing moderate or severe British Isles Lupus Assessment Group flares up to Week(Wk) 60; Maintaining corticosteroid dose ≤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; Maintaining corticosteroid dose ≤5mg/day or ≤baseline dose, whichever is lower, b/w Wk 24 & Wk 60
To demonstrate superiority of ianalumab 300 mg s.c. quarterly compared to placebo for SRI-4 & secondary objectives listed above
To evaluate: safety & tolerability, immunogenicity& characterize the PK of ianalumab 300 mg s.c (monthly or quarterly) | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 (SLE) according to EULAR/ACR SLE classification criteria at least 6 months prior to screening
Elevated serum titers at screening of Antinuclear Antibodies (≥1:80) as determined by a central laboratory with a SLE typical fluorescence pattern.
Currently receiving corticosteroids 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”
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
Weigh at least 35 kg at screening
| |
| E.4 | Principal exclusion criteria | Prior treatment with Ianalumab
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)
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 (HBV) or hepatitis C (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 laboratory values prior to randomization
Platelets <25000/mm^3 (<25 x 10^3/μL)
Hemoglobin (Hgb) <8.0 g/dL (<5 mmol/Lg), 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)
Severe organ dysfunction or life-threatening disease at screening
History of major organ, hematopoietic stem cell or bone marrow transplant
Presence of severe lupus kidney disease as defined by proteinuria above 2g/day or equivalent using spot urine protein creatinine ratio
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
History of hypersensitivity to drugs of similar class or oral CS or to any of the constituents of the study drugs (sucrose, L-histidine hydrochloride, L-histidine, polysorbate 20)
History of non-compliance with medical regiments or considered potentially unreliable
Use of other investigational drugs within 5 half lives of enrollment or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer, or longer if required by local regulations
Non-lupus conditions such as asthma, gout or urticaria, requiring intermittent or chronic treatment with systemic corticosteroids
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, 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.
US (and other countries, if locally required): sexually active males unless using barrier protection during intercourse while taking study treatment
Any surgical, medical, psychiatric or additional physical condition that may jeopardize participation in this study
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Proportion of participants achieving SRI-4 at Week 60 | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | |
| E.5.2 | Secondary end point(s) | 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 corticosteroiddose 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 maintaining between Week 24 and Week 60 a reduced corticosteroid dose of predniso(lo)ne ≤5 mg/day, or ≤baseline dose, whichever is lower
Proportion of participants with Adverse Events and
Serious Adverse Events
Clinical laboratory measurements
Vital signs
Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time
Ianalumab concentration in serum during the treatment and follow-up (up to the end of study) | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | 1,3,4,6,7 - Week 60
2 - Between Week 36 and Week 60
5 - from baseline to Week 60
8 - Between Week 24 and Week 60 | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Guatemala | | Brazil | | Canada | | China | | Israel | | Japan | | South Africa | | Thailand | | Turkey | | United States | | Bulgaria | | Czechia | | Hungary | | Poland | | Portugal | | Slovakia | | Spain | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 19 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
