Lupus nephritis MedDRA version: 9.1 Level: LLT Classification code 10025140 Term: Lupus nephritis
Conditions
Sponsors
Merck Serono International
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for inclusion in this study, subjects must fulfill the following criteria: 1. Diagnosis of systemic lupus erythematosus (SLE) satisfying at least 4 out of the 11 American College of Rheumatology (ACR) criteria 2. Positive antinuclear antibody (ANA) test results (HEp-2 ANA =1:80 and/or anti-dsDNA =30 IU/mL) 3. Renal biopsy performed within 12 months of study entry with histologic findings consistent with active International Society of Nephrology/Renal Pathology Society (ISN/PRS) class III or IV LN 4. Active LN as defined by proteinuria (urine protein/creatinine ratio >1.0) and hematuria (>10 RBCs/hpf with or without RBC casts). All other causes of hematuria of nonglomerular origin must be excluded 5. Renal disease activity at screening (based on proteinuria and hematuria) requiring high-dose corticosteroid treatment (maximum of 0.8 mg/kg/day, or 60 mg/day prednisone or prednisone equivalent, whichever is less) and initiation of MMF therapy Further inclusion criteria are described in the protocol Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study for any of the following reasons: 1. Renal disease unrelated to SLE (i.e., diabetes mellitus, renovascular disease whether or not associated with antiphospholipid syndrome) 2. Estimated glomerular filtration rate (GFR) =30 mL/min per 1.73 m2 at screening or end-stage renal disease requiring dialysis or transplant 3. Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment leading to inability provide informed consent and/or comply with the protocol 4. Comorbidities requiring corticosteroid therapy (such as asthma or inflammatory bowel disease) and/or preventing engagement in study conduct 5. Any treatment with MMF within the last 6 months, or known lack of efficacy to MMF treatment, whether on full dose or suboptimal dose due to MMF toxicity at any time 6. Treatment with CTX or azathioprine within the last 6 months Further exclusion criteria are described in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of atacicept compared to placebo in subjects with active LN receiving immunosuppressive therapy with MMF (mycophenolate mofetil).;Secondary Objective: The secondary objective of this study is to evaluate the safety and tolerability profile of atacicept in subjects with active LN requiring immunosuppressive therapy with MMF. Additional objectives of this study are: ? To evaluate the effect of atacicept on biomarkers pertinent to its mechanism of action and to LN disease activity ? To further characterize the pharmacokinetic and pharmacodynamic profiles of atacicept ? To identify genetic and genomic variations associated with drug response and disease activity and/or progression ;Primary end point(s): The primary endpoint is the proportion of subjects with confirmed complete response, partial response, and non-response at Week 52. The criteria for the response categories are defined as follows: Response categories {renal disease criteria adapted from (Ginzler, et al., 2005)}: ? Complete response (CR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate [GFR]), improvement in proteinuria (urine protein/creatinine ratio <0.5), and improvement in hematuria (< 5 red blood cells (RBCs)/high powered field (hpf) and no RBC casts by urine sediment analysis). Subjects cannot be treatment failures ? Partial response (PR): from baseline, a =10% worsening in renal function (assessed by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) and improvement in hematuria (= 50% reduction of RBCs from baseline and no RBC casts on urine sediment analysis). Subjects cannot be treatment failures ? Non-response (NR): Neither criteria for CR or PR are met. Subjects are also deemed NR if they have met a treatment failure definition, regardless of CR or PR status Secondary, additional, safety, health outcome, PK, p | — |
Countries
Czech Republic, United Kingdom
Outcome results
None listed