Peptide GAM Immunoadsorption Therapy in Autoimmune Membranous Nephropathy

Autoimmune Membranous Nephropathy Clinical Trial

— PRISM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03255447
• Other study ID #: R04240
• Status: Completed
• Phase: N/A
• Start date: November 30, 2016
• Est. completion date: April 3, 2019

Study information

• Verified date: June 2021
• Source: Manchester University NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 3, 2019
• Est. primary completion date: April 3, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Membranous Nephropathy
• Glomerulonephritis, Membranous
• Kidney Diseases

Intervention

Device:
• Immunoadsorption
Fresenius Globaffin

Locations

Country	Name	City	State
United Kingdom	Central Manchester University Hospital Foundation Trust	Manchester	Greater Manchester
United Kingdom	Royal Preston Hospital	Preston	Lancashire
United Kingdom	Salford Royal Infirmary	Salford	Lancashire

Sponsors (2)

Lead Sponsor	Collaborator
Manchester University NHS Foundation Trust	Fresenius AG

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum anti-PLA2R titres	Reduction in serum anti-PLA2R titres to normal range	14 days
Secondary	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
Secondary	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
Secondary	Serum anti-PLA2R titres	Kinetic modelling of serum anti-PLA2R levels	Day 14, 28, 56, 84, 168 and 365
Secondary	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
Secondary	Cost-effectiveness	Cost-effectiveness of treatment (Incremental cost-effectiveness ratio)	Day 14, 28, 56, 84, 168 and 365