Autoimmune Membranous NephropathyPRISMNCT03255447
Peptide GAM Immunoadsorption Therapy in Autoimmune Membranous Nephropathy
A study testing Immunoadsorption in people with Autoimmune Membranous Nephropathy, run by Manchester University NHS Foundation Trust at 3 sites in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Autoimmune Membranous Nephropathy
- What is being tested?
- Immunoadsorption
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 30 Nov 2016to 3 Apr 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Central Manchester University Hospital Foundation Trust
Manchester, Greater Manchester, M13 9WL
Royal Preston Hospital
Preston, Lancashire, PR2 9HT
Salford Royal Infirmary
Salford, Lancashire, M6 8HD
About this study
Official title: 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.
Read the 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.
- Conditions
- Autoimmune Membranous Nephropathy
- Being tested
- Immunoadsorption
- Keywords
- Idiopathic Membranous Nephropathy, Primary Membranous Nephropathy, Immunoadsorption, Apharesis
- Medical subject headings
- Glomerulonephritis, Membranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImmunoadsorptionDevice
Fresenius Globaffin
| Study group | Role | What they receive |
|---|---|---|
| Immunoadsorption therapy | Experimental | Peptide GAM immunoadsorption therapy Receives: Device: Immunoadsorption |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum anti-PLA2R titres
Reduction in serum anti-PLA2R titres to normal range
Measured: 14 days
Secondary outcomes (5)
The incidence of treatment related adverse events as defined by CTCAE v4.0
To assess the safety and tolerability of Immunoadosorption therapy
Measured: 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
Measured: Day 14, 28, 56, 84, 168 and 365
Serum anti-PLA2R titres
Kinetic modelling of serum anti-PLA2R levels
Measured: 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)
Measured: Day 14, 28, 56, 84, 168 and 365
Cost-effectiveness
Cost-effectiveness of treatment (Incremental cost-effectiveness ratio)
Measured: Day 14, 28, 56, 84, 168 and 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start30 Nov 2016
- Primary completion3 Apr 2019
- Study completion3 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune Membranous NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Collaborators
- Fresenius AG
- Responsible party
- Sponsor
- Investigators
- Sandip Mitra, Principal investigator, Central Manchester University Hospital Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255447
- Sponsor's protocol ID
- R04240
- Acronym
- PRISM
- Status last verified
- Jun 2021
- First submitted
- 11 Aug 2017
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Investigating the Safety and Feasibility of Peptide GAM Immunoadsorption in Anti-PLA2R Positive Autoimmune Membranous Nephropathy
- ClinicalTrials.gov ID
- NCT03255447
- Acronym / sponsor ID
- PRISM / R04240
- Conditions
- Autoimmune Membranous Nephropathy
- Keywords
- Idiopathic Membranous Nephropathy, Primary Membranous Nephropathy, Immunoadsorption, Apharesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Collaborators
- Fresenius AG
- Study start
- 30 Nov 2016 (actual)
- Primary completion
- 3 Apr 2019 (actual)
- Study completion
- 3 Apr 2019 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immunoadsorption therapy | Experimental | Device: ImmunoadsorptionPeptide GAM immunoadsorption therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImmunoadsorptionFresenius Globaffin | Device | Immunoadsorption therapy |
Primary outcome
Serum anti-PLA2R titres
Time frame: 14 days
Reduction in serum anti-PLA2R titres to normal range
5 secondary outcomes
The incidence of treatment related adverse events as defined by CTCAE v4.0
Time frame: Day 14, 28, 56, 84, 168 and 365
To determine the effect on disease activity (efficacy)
Time frame: Day 14, 28, 56, 84, 168 and 365
Serum anti-PLA2R titres
Time frame: Day 14, 28, 56, 84, 168 and 365
To determine the effect on Quality of life measures (EQ5D)
Time frame: Day 14, 28, 56, 84, 168 and 365
Cost-effectiveness
Time frame: Day 14, 28, 56, 84, 168 and 365
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sandip Mitra principal investigator
Central Manchester University Hospital Foundation Trust
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immunoadsorption in people with Autoimmune Membranous Nephropathy, run by Manchester University NHS Foundation Trust at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum anti-PLA2R titres (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.