Lupus Nephritis
Conditions
Keywords
SLE, Systemic Lupus Erythematosus (SLE), Kidney inflammation, Anti-BAFF-receptor, B cell depletion, Ianalumab, VAY736
Brief summary
This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN
Detailed description
This trial will evaluate the efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or ianalumab given every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous). using the 2003 International Society for Nephrology (ISN)/Renal Pathology Society (RPS) criteria).
Interventions
DRUGianalumab s.c. q4w
ianalumab s.c. q4w in addition to SoC
DRUGianalumab s.c. q12w
ianalumab s.c. q12w in addition to SoC
DRUGplacebo s.c.
placebo s.c. q4w in addition to SoC
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
This is a pivotal double-blind, randomized, placebo-controlled, multi-center three-arm study, evaluating at Week 72 efficacy and safety of ianalumab administered s.c. every 4 weeks or ianalumab administered s.c. every 12 weeks versus placebo, administered s.c. every 4 weeks, in adult participants with active LN receiving SoC. In addition, long-term efficacy, safety and tolerability will be collected up to Week 144.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Participants eligible for inclusion in this study must meet all of the following criteria: * Adult male and female participants aged 18 years or older at the time of screening * Weigh at least 35 kg at screening * Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria * Have a positive anti-nuclear antibody (ANA) test result; ANA titer ≥ 1:80 at screening visit based on central or local laboratory result * Active LN at screening, as defined by meeting the 3 following criteria: * Renal biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/
Exclusion criteria
. * UPCR ≥ 1.0 g/g on 24h urine collection at Screening * eGFR ≥ 25mL/min/1.73 m2. Participants with eGFR \< 30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in ≤ 50% of glomeruli * Newly diagnosed participants as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA * Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization * Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications * Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization * Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior randomization. Participant who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day) oral predniso(lo)ne. * Able to communicate well with the Investigator to understand and comply with the requirements of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and percentage of participants achieving stable Complete Renal Response (CRR) | Week 72 | The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 or no less than 85% of baseline, AND, 24-hour UPCR \<0.5 g/g) at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or ≥50% reduction from baseline | Week 72 | To demonstrate superiority of ianalumab, compared to placebo, in time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) \<0.5 g/g or ≥50% reduction from baseline up to Week 72 |
| Percentage of participants achieving stable Overall Renal Response (ORR), defined as achievement as either Complete Renal Response (CRR) or Partial Renal Response (PRR) | Week 48 | To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Overall Renal Response (ORR) at Week 48 |
| Incidence of stable Complete Renal Response (CRR) while maintaining daily corticosteroid dose ≤5 mg/day | Week 72 | To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Complete Renal Response (CRR) at Week 72 while maintaining daily corticosteroid dose ≤5 mg/day between Week 24 and Week 72 |
| Incidence of renal-related event or death | Week 72 | To demonstrate superiority of ianalumab, compared to placebo, in preventing renal-related event or death through Week 72 |
| Change in British Isles Lupus Activity Group (BILAG) score | Week 72 | To demonstrate superiority of ianalumab, compared to placebo in BILAG-2004 at Week 72 |
| Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score | Week 72 | To demonstrate superiority of ianalumab, compared to placebo, in FACIT-Fatigue at Week 72 |
| Number of participants with treatment-emergent Adverse Events (AEs) | Week 72 | AEs are any untoward sign or symptom that occurs during the study treatment |
| Ianalumab concentration in serum | Week 72 | To characterize the pharmacokinetics (PK) of ianalumab mean, median, minimum and maximum concentrations will be provided |
| Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time | Week 72 | To evaluate immunogenicity of ianalumab |
Countries
Argentina, Brazil, Canada, Chile, China, Colombia, Czechia, Estonia, France, Germany, Guatemala, Hong Kong, Hungary, India, Italy, Lithuania, Malaysia, Mexico, Romania, Singapore, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States, Vietnam
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed