Peptide GAM Immunoadsorption Therapy in Autoimmune Membranous Nephropathy (PRISM)

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

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.

Study Overview

• Status: Completed
• Conditions: Autoimmune Membranous Nephropathy
• Intervention / Treatment: Device: Immunoadsorption

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Central Manchester University Hospital Foundation Trust
  • Lancashire
    • Preston, Lancashire, United Kingdom, PR2 9HT
      • Royal Preston Hospital
    • Salford, Lancashire, United Kingdom, M6 8HD
      • Salford Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoadsorption therapy; Peptide GAM immunoadsorption therapy	Device: Immunoadsorption; Fresenius Globaffin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Collaborators: Fresenius AG
• Investigators: Principal Investigator: Sandip Mitra, Central Manchester University Hospital Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2016
• Primary Completion (Actual): April 3, 2019
• Study Completion (Actual): April 3, 2019

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Immunoadsorption; Primary Membranous Nephropathy; Idiopathic Membranous Nephropathy; Apharesis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, Membranous
• Other Study ID Numbers: R04240

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No