Systemic Lupus Erythematosus
Conditions
Keywords
Systemic Lupus Erythematosus, SLE, B cell depletion, SLEDAI-2K, BILAG-2004, SRI-4, ANA, ianalumab, VAY736
Brief summary
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
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. This extension study will last up to 7 years and includes the following three treatment periods: * a 3-year double-blind, randomized, placebo-controlled treatment period, evaluating the safety and efficacy of ianalumab or placebo (Period 1); * followed by a 2-year treatment period evaluating safety and efficacy of treatment withdrawal and open-label ianalumab administered s.c. monthly. * and an up to 2-year open-label, safety monitoring period (Period 3).
Interventions
DRUGPlacebo
Placebo s.c. monthly
DRUGIanalumab
Ianalumab s.c. monthly Ianalumab s.c. quarterly
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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. After the 3 year randomized, placebo-controlled period the study will continue as open-label to evaluate long term safety and efficacy of ianalumab, on or off-treatment, for an additional two years, followed by further monitoring of longer-term safety for up to two additional years
Eligibility
Sex/Gender
ALL
Age
12 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
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. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment-emergent Adverse events/Serious Adverse events | through study completion, up to approximately 324 weeks | Assessment of long-term safety and tolerability of ianalumab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who achieved Systemic Lupus Erythematosus Responder Index -4 (SRI-4) response | up to Week 324 | 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 |
| Proportion of participants who achieved Definition of Remission in SLE (DORIS) response | up to Week 324 | DORIS is defined as: * Clinical SLEDAI (cSLEDAI) = 0 (excluding serological items, anti-dsDNA and complement) * Physician global assessment (PhGA, scale 0-3) \< 0.5 * Current CS (predniso(lo)ne or equivalent) dose ≤ 5 mg/day * Patient may be on antimalarials, low dose glucocorticoids and/or stable immune-suppressive treatment including biologics. |
| Change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index | up to Week 324 | SLICC/ACR Damage Index is a measure of cumulative damage due to SLE |
| Average daily dose of corticosteroids administered | up to Week 324 | Evaluating the effect of ianalumab on corticosteroids intake |
| Annualized BILAG moderate or severe flare rate | up to Week 324 | 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 |
| Ianalumab serum concentrations during treatment and follow-up after last dose | up to Week 324 | To characterize the Pharmacokinetics (PK) of ianalumab |
| Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time. | up to Week 324 | To characterize the immunogenicity of ianalumab |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, France, Germany, Guatemala, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Poland, Portugal, Romania, Slovakia, South Africa, South Korea, Spain, Taiwan, Thailand, United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed