<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03255447</url>
  </required_header>
  <id_info>
    <org_study_id>R04240</org_study_id>
    <nct_id>NCT03255447</nct_id>
  </id_info>
  <brief_title>Peptide GAM Immunoadsorption Therapy in Autoimmune Membranous Nephropathy</brief_title>
  <acronym>PRISM</acronym>
  <official_title>Phase II Trial Investigating the Safety and Feasibility of Peptide GAM Immunoadsorption in Anti-PLA2R Positive Autoimmune Membranous Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Manchester University NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fresenius AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Manchester University NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Autoimmune Membranous Nephropathy is now understood to be a condition caused by the immune&#xD;
      system although the exact mechanism is not completely known. This study aims to remove the&#xD;
      offending part of the immune system using immunoadsorption to not only treat the disease but&#xD;
      also use the opportunity to better understand the mechanism of disease. This will allow more&#xD;
      targeted treatment in the future with less complications and side effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Membranous nephropathy (MN) is among the most common causes of nephrotic syndrome in adults&#xD;
      worldwide. The majority of patients will remain stable with either complete remission or&#xD;
      partial remission but approximately 20% will progress slowly to end stage renal disease&#xD;
      necessitating the need for renal replacement therapy (RRT).&#xD;
&#xD;
      Current standard therapy for primary (or autoimmune) membranous nephropathy is a regime of&#xD;
      rotating high dose steroids and immunosuppression was first described in the mid-nineties and&#xD;
      has been the mainstay of treatment since but comes with a high side effect burden.&#xD;
&#xD;
      Idiopathic membranous nephropathy is now understood to be an autoimmune disease characterised&#xD;
      by the presence of IgG autoantibodies to M-Type Phospholipase A2 Receptor (anti-PLA2R).&#xD;
      Immunoadsorption is a method of removing specific circulating immunoglobulins and has been&#xD;
      shown to remove over 80% of circulating IgG with a single session immunoadsorption of 2.5&#xD;
      plasma volumes, with albumin and antithrombin III almost unaffected. With multiple sessions&#xD;
      this can rise to over 98%.&#xD;
&#xD;
      Immunoadsorption therapy has been in use for a number of years and this study will use&#xD;
      Peptide GAM Immunoadsorption therapy developed by Fresenius Healthcare. This uses two&#xD;
      systems, the Art Universal and ADAsorb. The Art Universal became commercially available in&#xD;
      2005 and the ADAsorb in 2002.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2016</start_date>
  <completion_date type="Actual">April 3, 2019</completion_date>
  <primary_completion_date type="Actual">April 3, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serum anti-PLA2R titres</measure>
    <time_frame>14 days</time_frame>
    <description>Reduction in serum anti-PLA2R titres to normal range</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence of treatment related adverse events as defined by CTCAE v4.0</measure>
    <time_frame>Day 14, 28, 56, 84, 168 and 365</time_frame>
    <description>To assess the safety and tolerability of Immunoadosorption therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the effect on disease activity (efficacy)</measure>
    <time_frame>Day 14, 28, 56, 84, 168 and 365</time_frame>
    <description>Assessment of reduction in proteinuria level and change in eGFR from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum anti-PLA2R titres</measure>
    <time_frame>Day 14, 28, 56, 84, 168 and 365</time_frame>
    <description>Kinetic modelling of serum anti-PLA2R levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the effect on Quality of life measures (EQ5D)</measure>
    <time_frame>Day 14, 28, 56, 84, 168 and 365</time_frame>
    <description>To determine the effect on Quality of life measures (EQ5D)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>Day 14, 28, 56, 84, 168 and 365</time_frame>
    <description>Cost-effectiveness of treatment (Incremental cost-effectiveness ratio)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Autoimmune Membranous Nephropathy</condition>
  <arm_group>
    <arm_group_label>Immunoadsorption therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Peptide GAM immunoadsorption therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Immunoadsorption</intervention_name>
    <description>Fresenius Globaffin</description>
    <arm_group_label>Immunoadsorption therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy confirmed Primary Membranous Nephropathy within the last 3 years&#xD;
&#xD;
          -  Active disease despite 6 months of supportive care including ACEi or ARB (Active&#xD;
             disease defined as uPCR &gt; 300mg/mmol or 24 hour urinary protein &gt;3.5g/1.73m2)&#xD;
&#xD;
          -  Disease severity that in the physicians view warrants treatment prior to completion of&#xD;
             6 months supportive care&#xD;
&#xD;
          -  Anti-PLA2R titre &gt; 170 u/ml&#xD;
&#xD;
          -  Haemophilus and Pneumococcal vaccinations up to date&#xD;
&#xD;
          -  Above the age of 18&#xD;
&#xD;
          -  Able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of causes of secondary membranous nephropathy&#xD;
&#xD;
          -  eGFR &lt; 20ml/min&#xD;
&#xD;
          -  Treatment with steroids or immunosuppression (including but not limited to&#xD;
             cyclophosphamide, MMF or azathioprine) and Biologics (including but limited to&#xD;
             Rituximab or belimumab) within 6 months of screening&#xD;
&#xD;
          -  Therapeutic Plasma Exchange within 28 days of screening&#xD;
&#xD;
          -  Previous renal transplantation&#xD;
&#xD;
          -  Co-morbidity, which in physicians' view, would preclude patient from treatment with&#xD;
             immunoadsorption.&#xD;
&#xD;
          -  Pregnant at time of screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandip Mitra</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central Manchester University Hospital Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Central Manchester University Hospital Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <state>Greater Manchester</state>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Preston Hospital</name>
      <address>
        <city>Preston</city>
        <state>Lancashire</state>
        <zip>PR2 9HT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salford Royal Infirmary</name>
      <address>
        <city>Salford</city>
        <state>Lancashire</state>
        <zip>M6 8HD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>June 7, 2021</last_update_submitted>
  <last_update_submitted_qc>June 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Idiopathic Membranous Nephropathy</keyword>
  <keyword>Primary Membranous Nephropathy</keyword>
  <keyword>Immunoadsorption</keyword>
  <keyword>Apharesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Glomerulonephritis, Membranous</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03255447
org study id: R04240
nct id: NCT03255447
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serum anti-PLA2R titres
time frame: 14 days
description: Reduction in serum anti-PLA2R titres to normal range
measure: The incidence of treatment related adverse events as defined by CTCAE v4.0
time frame: Day 14, 28, 56, 84, 168 and 365
description: To assess the safety and tolerability of Immunoadosorption therapy
measure: To determine the effect on disease activity (efficacy)
time frame: Day 14, 28, 56, 84, 168 and 365
description: Assessment of reduction in proteinuria level and change in eGFR from baseline
measure: Serum anti-PLA2R titres
time frame: Day 14, 28, 56, 84, 168 and 365
description: Kinetic modelling of serum anti-PLA2R levels
measure: To determine the effect on Quality of life measures (EQ5D)
time frame: Day 14, 28, 56, 84, 168 and 365
description: To determine the effect on Quality of life measures (EQ5D)
measure: Cost-effectiveness
time frame: Day 14, 28, 56, 84, 168 and 365
description: Cost-effectiveness of treatment (Incremental cost-effectiveness ratio)
arm group label: Immunoadsorption therapy
arm group type: Experimental
description: Peptide GAM immunoadsorption therapy
intervention type: Device
intervention name: Immunoadsorption
description: Fresenius Globaffin
arm group label: Immunoadsorption therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Sandip Mitra
role: Principal Investigator
affiliation: Central Manchester University Hospital Foundation Trust
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Glomerulonephritis, Membranous
sharing ipd: No