Phase 3 Extension Study to Evaluate Long-term Safety of Ianalumab in Participants With Systemic Lupus Erythematosus (SIRIUS-SLE Extension).

Study Overview
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Brief Summary
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The purpose of this study is to evaluate long-term safety and tolerability of ianalumab in participants with systemic lupus erythematosus who have previously completed the treatment period in one of the two SIRIUS-SLE core studies (CVAY736F12301 or CVAY736F12302).

Detailed Description
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The purpose of this extension study is to evaluate long-term safety and tolerability of ianalumab administered s.c. monthly or quarterly, compared to monthly placebo, in adolescent and adult participants with anti-nuclear antibody (ANA)-positive systemic lupus erythematosus of moderate-to-severe disease activity, who have completed either CVAY736F12301 (SIRIUS-SLE 1) or CVAY736F12302 (SIRIUS-SLE 2) core studies.

Official Title
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A Randomized, Double-blind, Placebo-controlled Extension Study to Assess the Long-term Safety and Tolerability of Ianalumab in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE Extension)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Placebo
* Drug: Ianalumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed informed consent prior to participation in the extension study. Parent or legal guardian's signed informed consent and child's assent, if appropriate, are required before any assessment is performed for participants <18 years of age. Of note, if the participant reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study Informed Consent Form (ICF) at the next study visit. Participants must have participated in either one of the two SIRIUS-SLE core studies, CVAY736F12301 or CVAY736F12302, and have completed the treatment period through Week 60 without treatment discontinuation. In the judgement of the investigator, participants must be expected to clinically benefit from continued study treatment. Key Exclusion Criteria: Use of prohibited therapies. Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection which in the opinion of the investigator will place the participant at risk for participation. Plans for administration of live vaccines during the study period. Pregnant or nursing (lactating) women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, refusing or unable to use highly effective methods of contraception while on study treatment and for 6 months after stopping of study drug (or longer if required by concomitant medications). United States (and other countries, if locally required): sexually active males, unless they agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial is designed to evaluate long-term safety, tolerability and efficacy of two regimen of ianalumab versus placebo, given as monthly or quarterly subcutaneous (s.c.) injection
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ianalumab monthly<br>Ianalumab s.c. monthly | Drug: Ianalumab<br>* Ianalumab s.c. monthly Ianalumab s.c. quarterly<br>* Other names: VAY736;|
| Experimental: Ianalumab quarterly<br>Ianalumab s.c. quarterly | Drug: Ianalumab<br>* Ianalumab s.c. monthly Ianalumab s.c. quarterly<br>* Other names: VAY736;|
| Placebo Comparator: Placebo monthly<br>Placebo s.c. monthly | Drug: Placebo<br>* Placebo s.c. monthly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent Adverse events/Serious Adverse events | Assessment of long-term safety and tolerability of ianalumab | through study completion, up to approximately 91 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieved Systemic Lupus Erythematosus Responder Index -4 (SRI-4) response | 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 | up to Week 216 | 
| Change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index | SLICC/ACR Damage Index is a measure of cumulative damage due to SLE | up to Week 216 | 
| Average daily dose of oral corticosteroids administered | Evaluating the effect of ianalumab on corticosteroids intake | up to Week 216 | 
| Annualized BILAG moderate or severe flare rate | Annualized BILAG moderate or severe flare rate where moderate BILAG flare is defined as 2 or more new BILAG-2004 B items, and severe BILAG flare is defined as 1 or more new BILAG-2004 A items, compared to the previous visit | up to Week 216 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, SLE, B cell depletion, SLEDAI-2K, BILAG-2004, SRI-4, ANA, ianalumab, VAY736