Peptide GAM Immunoadsorption Therapy in Autoimmune Membranous Nephropathy

Study Overview
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Brief Summary
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Autoimmune Membranous Nephropathy is now understood to be a condition caused by the immune system although the exact mechanism is not completely known. This study aims to remove the offending part of the immune system using immunoadsorption to not only treat the disease but also use the opportunity to better understand the mechanism of disease. This will allow more targeted treatment in the future with less complications and side effects.

Detailed Description
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Membranous nephropathy (MN) is among the most common causes of nephrotic syndrome in adults worldwide. The majority of patients will remain stable with either complete remission or partial remission but approximately 20% will progress slowly to end stage renal disease necessitating the need for renal replacement therapy (RRT). Current standard therapy for primary (or autoimmune) membranous nephropathy is a regime of rotating high dose steroids and immunosuppression was first described in the mid-nineties and has been the mainstay of treatment since but comes with a high side effect burden. Idiopathic membranous nephropathy is now understood to be an autoimmune disease characterised by the presence of IgG autoantibodies to M-Type Phospholipase A2 Receptor (anti-PLA2R). Immunoadsorption is a method of removing specific circulating immunoglobulins and has been shown to remove over 80% of circulating IgG with a single session immunoadsorption of 2.5 plasma volumes, with albumin and antithrombin III almost unaffected. With multiple sessions this can rise to over 98%. Immunoadsorption therapy has been in use for a number of years and this study will use Peptide GAM Immunoadsorption therapy developed by Fresenius Healthcare. This uses two systems, the Art Universal and ADAsorb. The Art Universal became commercially available in 2005 and the ADAsorb in 2002.

Official Title
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Phase II Trial Investigating the Safety and Feasibility of Peptide GAM Immunoadsorption in Anti-PLA2R Positive Autoimmune Membranous Nephropathy

Conditions
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Autoimmune Membranous Nephropathy

Intervention / Treatment
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* Device: Immunoadsorption


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy confirmed Primary Membranous Nephropathy within the last 3 years Active disease despite 6 months of supportive care including ACEi or ARB (Active disease defined as uPCR > 300mg/mmol or 24 hour urinary protein >3.5g/1.73m2) Disease severity that in the physicians view warrants treatment prior to completion of 6 months supportive care Anti-PLA2R titre > 170 u/ml Haemophilus and Pneumococcal vaccinations up to date Above the age of 18 Able to provide informed consent Exclusion Criteria: Evidence of causes of secondary membranous nephropathy eGFR < 20ml/min Treatment with steroids or immunosuppression (including but not limited to cyclophosphamide, MMF or azathioprine) and Biologics (including but limited to Rituximab or belimumab) within 6 months of screening Therapeutic Plasma Exchange within 28 days of screening Previous renal transplantation Co-morbidity, which in physicians' view, would preclude patient from treatment with immunoadsorption. Pregnant at time of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunoadsorption therapy<br>Peptide GAM immunoadsorption therapy | Device: Immunoadsorption<br>* Fresenius Globaffin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum anti-PLA2R titres | Reduction in serum anti-PLA2R titres to normal range | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of treatment related adverse events as defined by CTCAE v4.0 | To assess the safety and tolerability of Immunoadosorption therapy | Day 14, 28, 56, 84, 168 and 365 | 
| To determine the effect on disease activity (efficacy) | Assessment of reduction in proteinuria level and change in eGFR from baseline | Day 14, 28, 56, 84, 168 and 365 | 
| Serum anti-PLA2R titres | Kinetic modelling of serum anti-PLA2R levels | Day 14, 28, 56, 84, 168 and 365 | 
| To determine the effect on Quality of life measures (EQ5D) | To determine the effect on Quality of life measures (EQ5D) | Day 14, 28, 56, 84, 168 and 365 | 
| Cost-effectiveness | Cost-effectiveness of treatment (Incremental cost-effectiveness ratio) | Day 14, 28, 56, 84, 168 and 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Membranous Nephropathy, Immunoadsorption, Apharesis, Idiopathic Membranous Nephropathy