Clinical Trials

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6 studies in Nephrology Collaborative Group (MNCG)

  1. A Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Study of H.P. Acthar Gel (Acthar) in Treatment-Resistant Subjects With Persistent Proteinuria and Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy (iMN)

    Rochester, Minn. View Summary

    A Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Study of H.P. Acthar Gel (Acthar) in Treatment-Resistant Subjects With Persistent Proteinuria and Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy (iMN)

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    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.

    NCT ID:

    NCT01386554

    IRB Number:

    11-003400

    Who can I contact for additional information about this study?

  2. "A Randomized Controlled Trial of Rituximab Versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (IMN)"

    Rochester, Minn., Jacksonville, Fla., Phoenix/Scottsdale, Ariz. View Summary

    "A Randomized Controlled Trial of Rituximab Versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (IMN)"

    Location:

    Rochester, Minn., Jacksonville, Fla., Phoenix/Scottsdale, Ariz.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    In IMN, experimental data suggests that B cells are involved in the pathogenesis of the disease. To date, the best proven therapy for patients with MN consists of the combined use of corticosteroids and cyclophosphamide (CYC). Since the mechanism of action of CYC includes suppression of various stages of the B cell cycle including B cell activation, proliferation, and differentiation and inhibition of immunoglobulin secretion, it lends credence to the hypothesis that B cells abnormalities are involved in the pathogenesis of MN. Given the key role of IgG antibodies in MN, it is reasonable to postulate that suppression of antibody production by depleting B cells may improve or even resolve the glomerular pathology and be reflected by a reduction in proteinuria. Thus, a case could be made for using an agent capable of selectively depleting B cells, and therefore halting the production of immunoglobulins against antigens potentially present in the glomeruli. This approach could stop the initiating sequence of pathogenic events and result in resolution of the. The P.I. believes that the application of selective B cell targeting with Rituximab (RTX) will prove at least equal, or even superior, both in the production of short term and long term control of the NS and be safer than any current therapeutic regimen used to treat MN. Based on this rationale, we conducted a pilot trial in 15 newly-biopsied patients (<3 years) with IMN and proteinuria >5g/24h despite ACEi/ARB use for >3months and systolic BP <130mmHg. Mean baseline creatinine was 1.4 mg/dl. Thirteen males and 2 females, median age 47 (range 33-63), were treated with RTX (1g) on days 1 and 15. At six months, patients who remained with proteinuria >3g/24 received a second identical course of RTX. Baseline proteinuria of 13.0±5.7g/24h (range 8.4-23.5) decreased to 6.0±7.0 g/24h (range 0.2-20) at 12 months (mean ± SD). In the fourteen patients who completed a 12 months follow-up complete remission (proteinuria <0.3g/24h) was achieved in 2 patients and partial remission (<3g/24h) in 7 patients. In 5 of these 7 patients, proteinuria was <1.5g/24h and follow up at 18 months showed that 3 of these 7 patients on PR achieved CR of proteinuria. Five patients did not respond. The mean drop in proteinuria from baseline to 12 months was 6.2± 5.1g (p=.002, paired t-test). There were a limited number of minor side-effects. Initial CD20+ B cell depletion was seen in all patients. However, at 3 months, CD20+ B cells were starting to recover with five patients >35 cells/µl (range 35-152).(50) These data contrasts with previous work by Ruggenenti et al. using RTX given weekly (375 mg/m2) for 4 weeks. Pharmacokinetic (PK) analysis showed that RTX levels in this 2-dose regimen were 50% lower compared to non-proteinuric patients, which could potentially result in undertreatment. Based on these results, we recently conducted a study postulating that in patients with MN, 4 weekly doses of RTX would result in more effective B cell depletion, a higher remission rate and maintaining of the same safety profile compared to patients treated with RTX dosed at 1g x 2. Twenty patients (11 failures to prior therapy) with MN and proteinuria >5g/24h received RTX (375mg/m2 x 4), with retreatment at 6 months regardless of proteinuria response. A detailed PK was conducted simultaneously along with immunological analyses of the adaptive immune compartment (T and B cells) to ascertain the impact of RTX on lymphocyte subpopulations. Baseline proteinuria of 11.9±4.9g/24h decreased to 4.2±3.8g/24h and 2.0±1.7g/24h at 12 and 24 months, respectively (p<0.001) while creatinine clearance increased from 72.4±33 at baseline to 88.4 ±31.5 ml/min/1.73m2 at 24 months (p=0.02). Of 18 patients who completed 24-months follow up, 4 are in complete remission, 12 are in partial remission (CR + PR = 80%), 1 has a limited response (>50% drop in P but >3.5g/24h) and 1 patient relapsed. When interpreting these results we should take into account that >50% of these patients had failed previous immunosuppressive therapy. This study also emphasizes that proteinuria is reduced gradually and may take several months to reach its nadir an observation that is in agreement with previous reports in patients with MN treated with prednisone in combination with a cytotoxic agent but without the short-term toxicity seen with alkylating agents. Kidney function remained stable or improved in all patients. Serum RTX levels were similar to those obtained with 2 doses of RTX. Four 4 doses of RTX did result in more effective B cell depletion but proteinuria reduction was basically identical to the results obtained using RTX 1000mg on days 1 and 15. Thus, we believe that this particular dosing regimen with retreatment at 6 months should be used in a randomized-control trial comparing RTX to Cyclosporine (the standard of care for IMN in the US). We believe that RTX will prove equal or superior to Cyclosporine in the treatment of MN and could represent the new standard of care for patients with this disease

    NCT ID:

    NCT01180036

    IRB Number:

    10-003372

    Who can I contact for additional information about this study?

    Rochester: Lori A Riess 507-266-1047
                        Shirley A Jennison 507-255-0231
    Scottsdale: Leslie F. Thomas, M.D. 480-342-0161
                        Andrea L. Francone, R.N. 480-342-1258
    Jacksonville: Nabeel Aslam, MD 904-953-7259
                        Jonathan J. Wright, MHSc, CCRP 904-953-7521
  3. Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy

    Rochester, Minn. View Summary

    Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    PRIMARY OBJECTIVES: I. To evaluate disease-free survival with pazopanib (pazopanib hydrochloride) as compared to placebo, defined as the time from randomization to the development of recurrent disease, second primary cancer (other than localized breast, localized prostate, or non-melanoma skin cancer) or death from any cause for patients with metastatic renal cell carcinoma (RCC) with no evidence of disease following metastatectomy. SECONDARY OBJECTIVES: I. To describe the overall survival of patients with advanced RCC randomly assigned to receive placebo or pazopanib for one year following metastatectomy to no evidence of disease (NED). II. To describe treatment- and (at recurrence) disease-related adverse events in the two treatment arms. III. To analyze quality-adjusted time without symptoms of disease or treatment (Q-TWiST) for subjects in the two treatment arms. IV. To characterize changes in patient-reported fatigue and (at recurrence) kidney cancer-related symptoms during and following treatment with pazopanib compared to placebo. V. To explore the association between plasma trough levels of pazopanib and disease-free and overall survival. VI. To prospectively bank preserved tissue from primary tumors and associated metastatic sites in patients with RCC. OUTLINE: Patients are randomized to 1of 2 treatment arms. ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for the first two years, every 6 months for the next 3 years, and then annually through 10 years.

    NCT ID:

    NCT01575548

    IRB Number:

    12-008951

    Who can I contact for additional information about this study?

    Rochester: Brian A. Costello 507-538-7623
                        


  4. BIIB023 for Subjects with Lupus Nephritis

    Rochester, Minn. View Summary

    BIIB023 for Subjects with Lupus Nephritis

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    Survival of patients with systemic lupus erythematosus (SLE) has improved greatly in the last decade, but lupus nephritis remains an important cause of morbidity and mortality in these patients. Recent studies have shown that we current therapies up to 50% of the patients with lupus nephritis fail to reach primary renal remission outcomes.  Thus, there is a need for more effective therapies in patients with lupus nephritis.

    The primary objective of the study is to assess the efficacy of BIIB023, an inhibitor of TWEAK (TNF-related weak inducer of apoptosis), as an add-on treatment to standard therapy compared with placebo in combination with standard therapy in the treatment of subjects with active, biopsy-proven lupus nephritis.

    There is substantial therapeutic rationale for inhibiting TWEAK in lupus nephritis: blocking the binding of TWEAK to Fn14 (fibroblast growth factor-inducible 14), BIIB023 attenuates TWEAK/Fn14 signaling and the downstream cellular responses of this signaling cascade; TWEAK induces the expression of proinflammatory mediators in both mesangial cells and podocytes, as well as in renal tubules, which may promote glomerulonephritis and tubulointerstitial inflammation. Since inflammation is considered to be a key mediator of tissue damage, TWEAK may promote tissue damage in lupus nephritis by promoting the recruitment of inflammatory infiltrates. TWEAK also acts in concert with other cytokines to promote renal tubular cell death. Thus, TWEAK may play an important pathogenic role in glomerulonephritis by promoting a local inflammatory environment and inducing tissue damage leading to progression to both glomerulosclerosis and tubulointerstitial fibrosis.

    Elevated levels of urinary TWEAK are observed in subjects with active lupus nephritis. Analyses of urinary TWEAK demonstrated that urinary TWEAK levels in biopsy-proven lupus nephritis patients are significantly higher than those found in SLE non-lupus nephritis patients and healthy controls. A significant association was found between urinary TWEAK levels and lupus nephritis disease activity as measured by the renal Systemic Lupus Erythematosus Disease Activity Index. Urinary TWEAK levels are also higher in patients undergoing a renal flare as compared with those with stable chronic renal disease and in patients undergoing renal as opposed to non-renal flare.

    Because TWEAK may promote multiple pathogenic activities locally in the kidney, it represents a promising target for therapeutic intervention. Inhibition of the TWEAK/Fn14 pathway with anti-TWEAK monoclonal antibodies has proven effective in multiple animal models of inflammatory diseases, suggesting that TWEAK blockade by BIIB023 may be clinically beneficial in lupus nephritis.

    The lack of a prominent impact on normal tissue homeostasis and adaptive immunity suggest that anti-TWEAK agents may have an attractive profile with respect to susceptibility to opportunistic infections and may therefore be combined with existing immunosuppressive therapies for LUPUS NEPHRITIS to achieve a novel more effective therapeutic approach without increased risk of infection.

    IRB Number:

    11-008028

    Who can I contact for additional information about this study?

    Fernando C. Fervenza, M.D., 507-266-7083, fervenza, fernando @mayo.edu
    Shirley Jennison, 507-255-0231, jennison.shirley@mayo.edu
  5. A Multicenter, Randomized, Prospective, Open-Label Trial of Rituximab in the Treatment of Progressive IgA Nephropathy

    Rochester, Minn. View Summary

    A Multicenter, Randomized, Prospective, Open-Label Trial of Rituximab in the Treatment of Progressive IgA Nephropathy

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease. . 2.0 OBJECTIVES 2.1 Primary Efficacy Endpoints: Percentage of patients in each group achieving complete or partial response as defined below: Complete Response: At 12 months 1. < 300 mg proteinuria/24 hours Pediatric Criteria: First morning void urine protein: creatinine ratio <0.3 2. No greater than a 10% reduction in baseline estimated GFR as determined by MDRD (4 point) formula Partial Response: At 12 months 1) > 50% reduction in 24 hour proteinuria 2) No greater than a 25% reduction in baseline estimated GFR as determined by MDRD formula No Response: At 12 months 1. A 50% reduction, unchanged or increasing proteinuria over baseline levels will be considered no response 2. A greater than a 30% reduction in baseline estimated GFR as determined by MDRD formula 2.2 Primary Safety Endpoints: - Incidence of Infusion Related Reactions: Defined as the development of hypotension, generalized pruritus, chills/rigors, angioedema and/or bronchospasm. - Pulmonary Complications: Defined as a hypoxia, pulmonary infiltrates and/or acute respiratory failure - Incidence of Major Infections: Defined as the development of pneumonia, complicated UTI/Pyelonephritis, Sepsis, and Meningitis. - Development of Progressive Multifocal Leukoencephalopathy (PML) 2.3 Secondary Exploratory Efficacy Endpoints: A) For patients in Groups 1 & 2 consenting to a repeat kidney biopsy at 12 months, a secondary endpoint will include the percentage of patients in experiencing a 25% increase in cortical fibrosis. The response rate will be semi-quantified by the change in cortical fibrosis as measured by changes in Sirius Red staining of interstitial collagen. A patient will be considered a complete or partial response or no response according to the following criteria: Complete: Less than 10% rise in cortical fibrosis as measured by Sirius Red staining and digital image analysis Partial: Rising cortical fibrosis > 10% but less than 25% No Response: Greater than 25% rise in cortical fibrosis over baseline levels-(if patient consents to repeat kidney biopsy)

    NCT ID:

    NCT00498368

    IRB Number:

    07-001944

    Who can I contact for additional information about this study?

    Rochester: Fernando C. Fervenza, M.D., Ph.D. 507-266-7961
                        Shirley A Jennison 507-255-0231


  6. Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

    Rochester, Minn. View Summary

    Nephrotic Syndrome Study Network Under the Rare Diseases Clinical Research Network

    Location:

    Rochester, Minn.

    Trial status:

    Open for Enrollment

    Why is this study being done?

    Idiopathic Nephrotic Syndrome (NS) is a rare disease syndrome responsible for approximately 12% of all causes of end-stage kidney disease (ESRD) and up to 20% of ESRD in children. Treatment strategies for Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN), the major causes of NS, include high dose prolonged steroid therapy, cyclophosphamide, cyclosporine A, tacrolimus, mycophenolate mofetil and other immunosuppressive agents, which all carry significant side effects. Failure to obtain remission using the current treatment approaches frequently results in progression to ESRD with its associated costs, morbidities, and mortality. In the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry, half of the pediatric patients with Steroid Resistant Nephrotic Syndrome required renal replacement therapy within two years of being enrolled in the disease registry. FSGS also has a high recurrence rate following kidney transplantation (30-40%) and is the most common recurrent disease leading to allograft loss. The prevailing classification of Nephrotic Syndrome categorizes patients into FSGS, MCD, and MN, if in the absence of other underlying causes, glomerular histology shows a specific histological pattern. This classification does not adequately predict the heterogeneous natural history of patients with FSGS, MCD, and MN. Major advances in understanding the pathogenesis of FSGS and MCD have come over the last ten years from the identification of several mutated genes responsible for causing Steroid Resistant Nephrotic Syndrome (SRNS) presenting with FSGS or MCD histopathology in humans and model organisms. These functionally distinct genetic disorders can present with indistinguishable FSGS lesions on histology confirming the presence of heterogeneous pathogenic mechanisms under the current histological diagnoses. The limited understanding of FSGS, MCD, and MN biology in humans has necessitated a descriptive classification system in which heterogeneous disorders are grouped together. This invariably consigns these heterogeneous patients to the same therapeutic approaches, which use blunt immunosuppressive drugs that lack a clear biological basis, are often not beneficial, and are complicated by significant toxicity. The foregoing shortcomings make a strong case that concerted and innovative investigational strategies combining basic science, translational, and clinical methods should be employed to study FSGS, MCD, and MN. It is for these reasons that the Nephrotic Syndrome Study Network is established to conduct clinical and translational research in patients with FSGS/MCD and MN.

    NCT ID:

    NCT01209000

    Who can I contact for additional information about this study?

    Rochester: Lori Riess 507-266-1047
                        Shirley Jennison 507-255-0231