Peptide GAM Immunoadsorption Therapy in Autoimmune Membranous Nephropathy

Not Applicable

Completed

• Conditions: Autoimmune Membranous Nephropathy
• Interventions: Device: Immunoadsorption

• Registration Number: NCT03255447
• Lead Sponsor: Manchester University NHS Foundation Trust

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-11-30
• Study First Submitted: 2017-08-11
• Study First Submitted QC: 2017-08-16
• Study First Posted: 2017-08-21
• Primary Completion: 2019-04-03
• Study Completion: 2019-04-03
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-07
• Last Update Posted: 2021-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Immunoadsorption therapy	Immunoadsorption	Peptide GAM immunoadsorption therapy

Primary Outcome Measures

Name	Time	Method
Serum anti-PLA2R titres	14 days	Reduction in serum anti-PLA2R titres to normal range

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Central Manchester University Hospital Foundation Trust; 🇬🇧 Manchester, Greater Manchester, United Kingdom

Salford Royal Infirmary; 🇬🇧 Salford, Lancashire, United Kingdom

Royal Preston Hospital; 🇬🇧 Preston, Lancashire, United Kingdom