Fernando C. Fervenza, M.D., Ph.D.

The purpose of this study is to assess the effectiveness of daratumumab SC in treating patients with  monoclonal immunoglobulin deposits (PGNMID) by assessing improvement in proteinuria at 12 months.

Additionally, to assess the safety of daratumumab SC in treating patients with PGNMID by assessing the incidence of major infections, eye complications, and cytopenias.

The purpose of this study is to assess the effectiveness and safety of daratumumab in inducing complete or partial remission in patients with active class III or IV (± V) lupus nephritis (LN) as measured by change in proteinuria and serum creatinine.

This study is being done to create a "resource" of samples that can be used to improve our ability to diagnose and treat MN, IgAN, MPGN, FSGS/MCD, Lupus Nephritis, AAV, other glomerular tubulo-interstitial disease.

Aim 1 (Epidemiology). To describe the disease trajectory under current clinical care; to estimate event rates for clinically meaningful outcomes; to identify patient characteristics (demographic, clinical, laboratory, environmental) associated with glomerular disease and non-renal complications of disease; to identify clinical predictors of short- and long-term outcomes, including therapeutic response; and to evaluate intermediate outcomes, such as proteinuria, as potential surrogates for longer-term outcomes.

Aim 2 (Biomarkers). To identify and characterize clinical, histological, molecular, and genetic biomarkers that are linked to glomerular disease, disease outcomes, or that might be used to improve disease classification; to identify and characterize biomarkers that may be employed in clinical practice or clinical trials to predict disease trajectory, disease activity, or response to therapy.

Aim 3 (Genetics). To understand the genetic architecture of the four glomerulopathies, including studies of germline sequence variation, somatic mutations, epigenetic changes, and transcriptomic profile, and their impact on disease presentation and clinical outcome; study gene-gene and gene-environment interactions that contribute to the development of the four glomerulopathies; and devise systems genetics approach to clarify pathogenesis.

Aim 4 (PROs). To identify Patient Reported Outcomes (PROs, e.g., symptom burden, physical function, quality of life) associated with primary glomerular diseases; to validate disease-specific instrument(s) to assess the impact of disease and its therapy on patients; and to test the associations of PROs with disease progression.

The purpose of this study is to assess the effectiveness of daratumumab SC in treating patients with  monoclonal immunoglobulin deposits (PGNMID) by assessing improvement in proteinuria at 12 months.

Additionally, to assess the safety of daratumumab SC in treating patients with PGNMID by assessing the incidence of major infections, eye complications, and cytopenias.

The purpose of this study is to evaluate the efficacy and safety of Avacopan together with low-dose glucocorticoid in the treatment of patients with crescentic IgAN and high risk of progression.

The purpose of this study is to assess the effectiveness, safety and pharmacokinetic (PK)/pharmacodynamic (PD) relationship of the human anti-CD38 antibody Felzartamab in patients with IgA Nephropathy (IgAN) at risk for progression.

The primary outcome of this study is to determine whether or not the B cell targeting with Rituximab is more effective than Cyclosporine in inducing long term remission of proteinuria.

Recent clinical success in the use of Rituximab in the treatment of Lupus nephritis and other forms immune complex glomerulonephritis has led to its investigation in the treatment of IgA nephropathy. Because IgA class antibodies have comparatively short half-lives and that deposition of polymeric forms of IgA contributes to glomerular injury, we speculate that the reduction of circulating IgA may reduce proteinuria and injury in patients with IgA nephropathy. Moreover, the absence of prospective trials in the treatment of IgA disease and the lack of consensus for long-term treatment, the superior side-effect profile of this form of therapy may lead to significant advances in the treatment of this prevalent from of glomerulonephritis.

The primary objectives of this trial are as follows:

• to compare the achievement of a partial remission (PR) or complete remission (CR) in urinary protein: creatinine ratio (Up/c ratio) in patients treated with fresolimumab versus placebo
• to compare the safety profile of patients treated with fresolimumab versus placebo

The secondary objectives are as follows:

• To compare the reduction in proteinuria in patients treated with fresolimumab versus placebo
• To evaluate fresolimumab dose-dependent reduction in proteinuria
• To compare the change in renal function (estimated glomerular filtration rate [eGFR]) in patients treated with fresolimumab versus placebo
• To evaluate the multiple-dose pharmacokinetics of fresolimumab

The purpose of this study is to evaluate the effect of cemdisiran on proteinuria in adults with immunoglobulin A nephropathy (IgAN), who excrete >1 gram (gm) of protein per day despite standard of care, which includes treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). These patients are at high risk for progression of kidney disease, which can result in end-stage renal failure.

This is an open-label, multicentre study to characterize the safety and effectiveness of the human anti-CD38 antibody MOR202 in adult subjects with in Anti-PLA2R Antibody Positive Membranous Nephropathy (newly diagnosed/relapsed/refractory).

The purpose of this study is evaluate if abatacept is effective and safe in decreasing the level of protein loss in the urine in patients with excessive loss of protein in the urine (nephrotic syndrome) due to either focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Candidates must have a prior kidney biopsy with either diagnosis. Another kidney biopsy will not be required as part of the study. Candidates must have failed or be intolerant of prior therapy for their kidney disease. The failed or intolerant therapy must include corticosteroids and at least one other drug. Candidates can be adults and children over the age of 6. Abatacept will be administered by venous infusion every 4 weeks.

The purpose of this study is to evaluate the effectiveness, safety, and pharmacokinetics of obinutuzumab compared with placebo in patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.

The purpose of this study is to evaluate the effectivess and safety of Obinutuzumab as compared to Tacrolimus in patients with Primary Membranous Nephropath (pMN).

The purpose of this study is to determine whether Rituximab therapy is safe and effective in treating patients with the kidney condition, focal segmental glomerulosclerosis (FSGS), that is no longer responsive to traditional therapies.

The purpose of this study is to assess the effect of aliskiren to keep protein from spilling into the urine in patients who have idiopathic membranous nephropathy.

The aim of this trial is to evaluate the effect of avacopan treatment on renal disease activity in patients with complement component 3 glomerulopathy (C3G).

The purpose of this study is to determine the long-term nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with primary and genetic focal segmental glomerulosclerosis (FSGS).

The purpose of this study is to provide nephrologists with additional clinical evidence regarding the efficacy and safety of Acthar in subjects with treatment-resistant idiopathic membranous nephropathy. Approximately sixty (60) subjects will be randomized in this double-blind, parallel-group, placebo-controlled, multicenter study comparing Acthar and Placebo administered 2 times per week for a 24-week treatment period followed by a 24-week observation period. The primary objective of this study is to assess the proportion of treatment-resistant subjects (defined as subjects who either have had no response or have suffered a relapse after achieving a partial response to their most recent standard treatment regimen) who have a complete or partial remission of proteinuria in nephrotic syndrome due to idiopathic membranous nephropathy after 24 weeks of treatment.

The purpose of this study is to enroll 12 patients with immunosuppression-dependent or immunosuppression/treatment-resistant primary FSGS, or contraindication/patient refusal to take high dose corticosteroids, to test the effectiveness and safety of obinutuzumab in inducing complete or partial remission of proteinuria.

Patients with immunosuppression-dependent or immunosuppression/treatment-resistant primary FSGS or contraindication/patient refusal to take high dose corticosteroids, will receive obinutuzumab 1 gram on day 1 and 1 gram on day 15, given intravenously and then an identical course at 6 months.

This study is designed to answer whether patients with progressive IgA nephropathy, who receive Acthar (ACTH) gel injection at a dose of 80 units subcutaneously twice weekly for 6 months is effective in inducing improvement in proteinuria and renal function.

The purpose of this registry is to establish a database of patients diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or immunoglobulin A nephropathy (IgAN), to advance the diagnosis and care of patients with glomerular diseases.

The aims of this study are to (1) determine the pathological spectrum of C3G, using clinical features available at diagnosis; clinical features over time; renal biopsy results at presentation and (where available) over time and (2) to determine if there are histological features within the renal biopsy that enable us to meaningfully stratify patients into prognostic groups.

Membranous glomerulopathy (MN) is still the most common glomerular disease associated with nephrotic proteinuria (NS). Up to 40% of patients reach end stage renal failure (ESRD), making MN the 2nd or 3rd most common cause of ESRD caused by a primary glomerulopathy. Current treatment options include corticosteroids, alkylating agents, and cyclosporin, but their use is controversial and the associated adverse effects and high cost temper their usage. Experimental data in MN suggests that B cell activation results in immunoglobulin deposition along the glomerular basement membrane causing injury to the membrane and subsequent proteinuria. Drugs that non-selectively inhibit B cells and, these pathogenic antibodies, are closely associated with improved outcomes. Based on the rationale that selective depletion of B cells in humans would prevent the production of nephrotoxic immunoglobulins and subsequent renal injury we recently treated 15 patients with MN with rituximab 1g i.v. twice (day 1 and day 15). Baseline proteinuria of 13.0±5.5g/24h decreased to 9.1±7g, 9.7±8g and 6.5±6 g/24h at 3, 6, and 9 months, respectively (mean ± SD). Analysis of the pharmacokinetic data obtained from this study, however, suggests that in heavily nephrotic patients, rituximab dosed in this fashion results in patients being under-treated. The present study propose to test the hypothesis that rituximab, given in accordance to the standard lymphoma protocol (375mg/m2 x 4), will result in a more effective and profound depletion of B cells, a more complete suppression of pathogenic antibodies, and a higher remission rate of the NS while maintaining a favorable safety profile.

This study is being done to see if daratumumab is safe and effective in the treatment of proliferative glomerulonephritis with monoclonal immune deposits (PGNMID) and C3 glomerulopathy associated with monoclonal gammopathy (C3GN). This is an inflammatory disease in the kidney due to the production of abnormal proteins. There are no known standard effective treatments for patients with PGNMID and C3GN secondary to monoclonal gammopathy. These diseases are caused by abnormal production of proteins (monoclonals) by abnormal clones. Daratumamb has been shown to be effective in treating patients with multiple myeloma a disease which also caused by over production of monoclonal proteins from abnormal clones. Everyone in this study will receive daratumumab.

Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients.

In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium.

Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.

Multicenter, multiple dose study to examine the effect of H.P. Acthar® Gel (repository corticotropin injection) in adult subjects with idiopathic focal segmental glomerulosclerosis (FSGS) who have failed to achieve remission with, or who are intolerant of, 1 or more previous immunosuppressive therapies.