<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/NCT04456816</url>
  </required_header>
  <id_info>
    <org_study_id>SynAct-CS003</org_study_id>
    <nct_id>NCT04456816</nct_id>
  </id_info>
  <brief_title>A Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Treatment With AP1189 in Patients With iMN and Severe Proteinuria</brief_title>
  <official_title>An Exploratory, Randomized, Double-blind, Multicenter, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AP1189 Versus Placebo Administered for 12 Weeks as an add-on to Patients, in ACE Inhibitor or Angiotensin II Receptor Blocker Treatment, With Idiopathic Membranous Nephropathy and Severe Proteinuria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SynAct Pharma Aps</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SynAct Pharma Aps</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study&#xD;
      with repeated doses of AP1189. The study population will consist of patients with idiopathic&#xD;
      membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin&#xD;
      II receptor blocker treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study&#xD;
      with repeated doses of AP1189. The study population will consist of patients with idiopathic&#xD;
      membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin&#xD;
      II receptor blocker treatment.&#xD;
&#xD;
      Following a successful screening, subjects who fulfill the enrollment criteria will be&#xD;
      randomized in a 2:1 ratio in group A and B:&#xD;
&#xD;
        -  Group A (12 subjects): AP1189 dose 100 mg, once daily for 12 weeks (28 days) as an&#xD;
           add-on to any ongoing treatment, including ACE inhibitors/ angiotensin II receptor&#xD;
           blocker&#xD;
&#xD;
        -  Group B (6 subjects): placebo for 12 weeks (28 days) as an add-on to any ongoing&#xD;
           treatment including ACE inhibitors/ angiotensin II receptor blocker.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 31, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Exploratory, randomized, double-blind, multi-center, placebo-controlled 12-weeks study with repeated doses of AP1189</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Event</measure>
    <time_frame>Week 12</time_frame>
    <description>Evaluation of Adverse Event</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious Adverse Events</measure>
    <time_frame>Week 12</time_frame>
    <description>Evaluation of Serious Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ALAT change in plasma samples</measure>
    <time_frame>Week 12</time_frame>
    <description>Evaluation of ALAT compared with baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ASAT change in plasma samples</measure>
    <time_frame>Week 12</time_frame>
    <description>Evaluation of ASAT compared with baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total bilirubin change in plasma samples</measure>
    <time_frame>Week 12</time_frame>
    <description>Evaluation of total bilirubin compared with baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Alkaline phosphatase change in plasma samples</measure>
    <time_frame>Week 12</time_frame>
    <description>Evaluation of alkaline phosphatase compared with baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Protein change in 24 hours urinary protein excretion</measure>
    <time_frame>Week 12</time_frame>
    <description>Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Albumin change in 24 hours urinary protein excretion</measure>
    <time_frame>Week 12</time_frame>
    <description>Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">23</enrollment>
  <condition>Nephrotic Syndrome Due to Idiopathic Membranous Nephropathy</condition>
  <condition>Severe Proteinuria Due to Idiopathic Membranous Nephropathy</condition>
  <arm_group>
    <arm_group_label>100 mg AP1189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>100 mg AP1189</intervention_name>
    <description>100 mg AP1189 tablet</description>
    <arm_group_label>100 mg AP1189</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent has been obtained prior to initiating any study-specific&#xD;
             procedures&#xD;
&#xD;
          -  Male and female subjects, 18 to 85 years of age diagnosed with iMN within 6 months&#xD;
             prior to inclusion&#xD;
&#xD;
          -  Diagnosed as anti-PLA2-Receptor positive by local laboratory within 6 months prior to&#xD;
             inclusion&#xD;
&#xD;
          -  Severe proteinuria defined by a U-protein/creatinine ratio &gt;3.0 g/g and/or&#xD;
             U-albumin/creatinine ratio &gt;2.0 g/g and a P-albumin below the lower normal limit&#xD;
&#xD;
          -  eGFR &gt; 30 ml/min/1.73m2&#xD;
&#xD;
          -  Treated with ACE- inhibitors or angiotensin II receptor blocker for a minimum of 1&#xD;
             months with a stable systemic arterial blood pressure OR treatment with ACE inhibitors&#xD;
             and/or angiotensin receptor blocker was excluded or discontinued due to hypotension,&#xD;
             intolerance or other side effect&#xD;
&#xD;
        Only Denmark and Norway:&#xD;
&#xD;
          -  Females of child-bearing potential using reliable means of contraception or are&#xD;
             post-menopausal&#xD;
&#xD;
          -  Females of childbearing potential with negative pregnancy test at screening and&#xD;
             baseline&#xD;
&#xD;
        Only Sweden:&#xD;
&#xD;
          -  Post-menopausal women or women who are surgically sterilized.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in any other study involving investigational drug(s) during the study&#xD;
             and within 4 weeks prior to study entry&#xD;
&#xD;
          -  Clinicial findings that in the opinion of the investigator would suggest condition(s)&#xD;
             other than iMN as a major cause of severe proteinuria&#xD;
&#xD;
          -  Major surgery within 8 weeks prior to screening or planned surgery within 1 month&#xD;
             following randomization&#xD;
&#xD;
          -  Blood pressure with systolic pressure above 160 mmHg and/or diastolic pressure above&#xD;
             100 mmHg despite antihypertensive treatment will in all cases be considered&#xD;
             &quot;uncontrolled&quot;&#xD;
&#xD;
          -  Treated with systemic corticosteroids, or other immune suppressive, or immune&#xD;
             modulating compounds within 4 weeks prior to screening and during the entire treatment&#xD;
             period and until the final visit&#xD;
&#xD;
          -  Treated with rituximab within 12 months of screening&#xD;
&#xD;
          -  Evidence of active malignant disease&#xD;
&#xD;
          -  Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease&#xD;
             where flares are commonly treated with oral or parenteral corticosteroids&#xD;
&#xD;
          -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system,&#xD;
             pulmonary, renal, hepatic, endocrine or gastrointestinal disease&#xD;
&#xD;
          -  Pregnant women or nursing mothers&#xD;
&#xD;
          -  History of alcohol, drug, or chemical abuse within the 6 months prior to screening&#xD;
&#xD;
          -  Any condition that in the view of the investigator would suggest that the patient is&#xD;
             unable to comply with study protocol and procedures&#xD;
&#xD;
        Only Sweden:&#xD;
&#xD;
          -  Females of child-bearing potential.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henrik Birn, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus Universitetshospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Irene Sandholdt</last_name>
    <phone>+45 2015 7033</phone>
    <email>isa@croxxmed.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Birgitte Telmer, MD</last_name>
    <phone>+45 2015 1221</phone>
    <email>bte@croxxmed.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Aarhus Universitetshospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Henrik Birn, Professor</last_name>
      <phone>+45 40460271</phone>
      <email>henrbirn@rm.dk</email>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>November 16, 2022</last_update_submitted>
  <last_update_submitted_qc>November 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Proteinuria</mesh_term>
    <mesh_term>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
    <mesh_term>Glomerulonephritis, Membranous</mesh_term>
  </condition_browse>
  <!-- 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/NCT04456816
org study id: SynAct-CS003
nct id: NCT04456816
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study
      with repeated doses of AP1189. The study population will consist of patients with idiopathic
      membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin
      II receptor blocker treatment.
This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study
      with repeated doses of AP1189. The study population will consist of patients with idiopathic
      membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin
      II receptor blocker treatment.

      Following a successful screening, subjects who fulfill the enrollment criteria will be
      randomized in a 2:1 ratio in group A and B:

        -  Group A (12 subjects): AP1189 dose 100 mg, once daily for 12 weeks (28 days) as an
           add-on to any ongoing treatment, including ACE inhibitors/ angiotensin II receptor
           blocker

        -  Group B (6 subjects): placebo for 12 weeks (28 days) as an add-on to any ongoing
           treatment including ACE inhibitors/ angiotensin II receptor blocker.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Exploratory, randomized, double-blind, multi-center, placebo-controlled 12-weeks study with repeated doses of AP1189
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Adverse Event
time frame: Week 12
description: Evaluation of Adverse Event
measure: Serious Adverse Events
time frame: Week 12
description: Evaluation of Serious Adverse Events
measure: ALAT change in plasma samples
time frame: Week 12
description: Evaluation of ALAT compared with baseline
measure: ASAT change in plasma samples
time frame: Week 12
description: Evaluation of ASAT compared with baseline
measure: Total bilirubin change in plasma samples
time frame: Week 12
description: Evaluation of total bilirubin compared with baseline
measure: Alkaline phosphatase change in plasma samples
time frame: Week 12
description: Evaluation of alkaline phosphatase compared with baseline
measure: Protein change in 24 hours urinary protein excretion
time frame: Week 12
description: Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion
measure: Albumin change in 24 hours urinary protein excretion
time frame: Week 12
description: Change of albumin in urine excretion compared to baseline measured in 24 h urinary protein excretion
arm group label: 100 mg AP1189
arm group type: Experimental
description: 100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
arm group label: Placebo
arm group type: Experimental
description: Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
intervention type: Drug
intervention name: 100 mg AP1189
description: 100 mg AP1189 tablet
arm group label: 100 mg AP1189
intervention type: Drug
intervention name: Placebo
description: Matching placebo tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Henrik Birn, Professor
role: Principal Investigator
affiliation: Aarhus Universitetshospital
last name: Irene Sandholdt
phone: +45 2015 7033
email: isa@croxxmed.com
last name: Birgitte Telmer, MD
phone: +45 2015 1221
email: bte@croxxmed.com
facility: 
status: Recruiting
contact: 
country: Denmark
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Proteinuria
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Glomerulonephritis, Membranous