Study of Safety, Efficacy and Tolerability of Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the efficacy and safety of subcutaneous secukinumab 300 mg compared to placebo, in combination with standard of care therapy (SoC), in subjects with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features).

Detailed Description
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A two-year, phase III randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the safety, efficacy, and tolerability of 300 mg s.c. secukinumab versus placebo, in combination with SoC therapy, in patients with active lupus nephritis

Official Title
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A Two-year, Phase III Randomized, Double-blind, Parallel-group, Placebo-controlled Trial to Evaluate the Safety, Efficacy, and Tolerability of 300 mg s.c. Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: secukinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female subjects aged 18 - 75 years old at the time of Baseline. Confirmed diagnosis of: SLE as defined by the American College of Rheumatology (ACR), OR LN as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies. Active lupus nephritis: International Society of Neurology/Renal Pathology Society (ISN/RPS) Class III or IV LN [excluding III (C), IV-S (C) and IV-G (C)]; subjects are permitted to have co-existing Class V. UPCR ≥1 at Screening. Estimated Glomerular Filtration Rate (eGFR) >30 mL/min/1.73 m2. Active urinary sediment. Exclusion Criteria: Severe renal impairment and subjects requiring dialysis dialysis within the previous 12 months before Screening. Significant medical Problems like myocarditis, pericarditis, severe manifestations of neuropsychiatric SLE (NPSLE). Cyclophosphamide (CYC) use (i.v. or oral) or more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within the month prior to Baseline. Active ongoing inflammatory diseases. Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17 or the IL-17 receptor. Ongoing infections or malignant process. Pregnant or lactating women. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: secukinumab<br>secukinumab 300 mg s.c. | Drug: secukinumab<br>* STUDY DRUG<br>* Other names: AIN457;|
| Placebo Comparator: placebo<br>secukinumab placebo s.c. | Drug: secukinumab<br>* STUDY DRUG<br>* Other names: AIN457;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving Complete Renal Response (CRR) | Proportion of subjects achieving protocol-defined CRR | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour Urine Protein-to Creatinine Ratio (UPCR) | Change from Baseline in 24-hour UPCR | Week 52 | 
| Proportion of subjects achieving Partial Renal Response (PRR) | Proportion of subjects achieving protocol-defined PRR | Week 52 | 
| Average daily dose of oral corticosteroids | Average daily dose of oral corticosteroids compared to placebo | Week 16 to Week 52 | 
| Proportion of subjects achieving PRR | Proportion of subjects achieving PRR | Week 24 | 
| Time to achieve CRR | Time to achieve CRR | Baseline to Week 52 | 
| Time to achieve PRR | Time to achieve PRR | Baseline to Week 52 | 
| Time to achieve UPCR ≤ 0.5 mg/mg | Time to achieve first morning void UPCR ≤ 0.5 mg/mg | Baseline to Week 52 | 
| Improvement in FACIT-Fatigue© | Improvement in FACIT-Fatigue© mean change of score compared to placebo The FACIT Fatigue Scale measures an individual's level of fatigue during their usual daily activities. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued) | Baseline to Week 52 | 
| Improvement in SF-36 PCS mean | Improvement in SF-36 PCS mean change compared to placebo | Baseline to Week 52 | 
| Improvement in LupusQoL Physical Health mean | Improvement in LupusQoL Physical Health mean change of score compared to placebo | Baseline to Week 52 | 
| Incidence of Treatment-emergent AEs (TEAEs) / SAEs | Incidence of Treatment-emergent AEs (TEAEs) / SAEs from Baseline to Week 52; vital signs and body measurements, standard chemistry and hematology | Baseline to Week 52 | 
| Proportion of subjects with CRR at Week 104 within subjects who had achieved CRR at Week 52 | Estimate the proportion of subjects with CRR at Week 104 within subjects who had achieved CRR at Week 52 in the secukinumab group | Week 52 to Week 104 | 
| Proportion of subjects with improved or maintained renal response at Week 104 | Estimate the proportion of subjects with improved or maintained response (PRR or CRR) in subjects who had achieved at least PRR at Week 52 in the secukinumab group | Week 52 to Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, LN, secukinumab, renal biopsy, eGFR, UPCR, SoC background therapy