<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/NCT04418024</url>
  </required_header>
  <id_info>
    <org_study_id>AG10-333</org_study_id>
    <secondary_id>2018-004670-10</secondary_id>
    <nct_id>NCT04418024</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Polyneurophathy</brief_title>
  <acronym>ATTRibute-PN</acronym>
  <official_title>A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects With Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eidos Therapeutics, a BridgeBio company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eidos Therapeutics, a BridgeBio company</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with&#xD;
      placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ** See updated study design under ClinicalTrials.gov Identifier NCT04882735. **&#xD;
&#xD;
      Transthyretin amyloid polyneuropathy (ATTR-PN), also called &quot;Familial Transthyretin-Mediated&#xD;
      Amyloid Polyneuropathy (FAP)&quot; is a hereditary condition caused by mutations in the TTR gene.&#xD;
      It is estimated that around 10,000 people in the world are affected.&#xD;
&#xD;
      In ATTR-PN, amyloid builds up in the nerves that detect temperature, pain, and touch.&#xD;
      Patients with ATTR-PN can experience a loss of sensation, tingling, numbness, or pain in the&#xD;
      hands and feet (also called peripheral neuropathy).&#xD;
&#xD;
      In this study Eidos is researching the investigational drug AG10 800mg (2 tablets)&#xD;
      administered orally twice a day. Through the study, Eidos wants to evaluate the efficacy and&#xD;
      safety of AG10 in patients with ATTR-PN versus placebo.&#xD;
&#xD;
      This is an 18 month, placebo-controlled study. This means that, during the 18 month study,&#xD;
      investigators conducting the research and study participants will not know whether the study&#xD;
      participant is receiving AG10 or placebo.&#xD;
&#xD;
      The primary outcome of the study is the difference between AG10 and placebo groups in the&#xD;
      Modified Neurologic Impairment Score +7 (mNIS+7) at 18 months of treatment versus baseline.&#xD;
&#xD;
      At the end of 18 months, participants may be eligible to receive investigational AG10, and&#xD;
      there is no placebo. This is called an &quot;open label extension.&quot; This part of the study may&#xD;
      help us better understand the safety related to taking AG10 over a longer period of time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    After a careful review of the currently available treatments worldwide for patients with&#xD;
    ATTR-polyneuropathy, Eidos has made the decision to halt the current study design.&#xD;
  </why_stopped>
  <start_date type="Actual">October 21, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment</measure>
    <time_frame>18 Months</time_frame>
    <description>Evaluate the difference between the AG10 and placebo groups in Modified Neuropathy Impairment which is a composite scale that asses,in part, muscle weakness, sensory loss, and decreased muscle stretch reflexes. It is calculated on a scale of 0 to 304 with higher scores indicating a worsening of the disease.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy</condition>
  <arm_group>
    <arm_group_label>AG10 800 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TTR stabilizer administered orally twice daily (BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered orally twice daily (BID)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AG10</intervention_name>
    <description>TTR stabilizer administered orally twice daily (BID)</description>
    <arm_group_label>AG10 800 mg</arm_group_label>
    <other_name>Oral AG10</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Non-active control</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Oral Tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be male or female ≥18 to ≤90 years of age;&#xD;
&#xD;
          -  Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIa) of ATTR-PN and an&#xD;
             established diagnosis of ATTR-PN as defined by physical exam findings and/or&#xD;
             neurophysiological test findings consistent with the diagnosis of ATTR-PN;&#xD;
&#xD;
          -  Have an NIS of 5 to 130 (inclusive) during screening;&#xD;
&#xD;
          -  Have a nerve conduction studies (NCS) score [sum of the sural sensory nerve action&#xD;
             potential (SNAP), tibial compound muscle action potential (CMAP), ulnar SNAP, ulnar&#xD;
             CMAP, and peroneal CMAP] of ≥2 points during screening. NCS is a component of mNIS+7;&#xD;
&#xD;
          -  Have a mutation consistent with ATTR-PN either documented in medical history or&#xD;
             confirmed by genotyping obtained at Screening prior to randomization. *No genetic&#xD;
             testing is needed for subjects who are recipients of domino liver transplants;&#xD;
&#xD;
          -  Have an anticipated survival of ≥2 years&#xD;
&#xD;
          -  Have Karnofsky performance status ≥60 %;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Had a prior liver transplantation or is planning to undergo liver transplantation with&#xD;
             a wild-type organ graft as treatment for symptomatic ATTR-PN during the study period.&#xD;
&#xD;
        Note: Recipients of a &quot;domino&quot; liver transplant from an ATTR-PN donor who have developed&#xD;
        ATTR-PN mediated by their graft are allowed under this protocol, as long as&#xD;
        re-transplantation to treat ATTR-PN is not planned during the study period and meets all&#xD;
        other eligibility criteria;&#xD;
&#xD;
          -  Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example,&#xD;
             autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;&#xD;
&#xD;
          -  Has Vitamin B-12 levels below the lower limit of normal (LLN);&#xD;
&#xD;
          -  Has clinical evidence of untreated hyper/hypothyroidism;&#xD;
&#xD;
          -  Has leptomeningeal TTR amyloidosis;&#xD;
&#xD;
          -  Has Type 1 diabetes;&#xD;
&#xD;
          -  Has had Type 2 diabetes for ≥5 years;&#xD;
&#xD;
          -  Has active hepatitis B or C or known human immunodeficiency virus (HIV) infection;&#xD;
&#xD;
          -  Has NYHA heart failure classification &gt;Class II&#xD;
&#xD;
          -  Had a malignancy within 2 years, except for basal or squamous cell carcinoma of&#xD;
&#xD;
          -  Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or other gene&#xD;
             silencing agents, marketed drug products lacking a label indication for ATTR- PN&#xD;
             (e.g., diflunisal, doxycycline), natural products or derivatives used as unproven&#xD;
             therapies for ATTR-PN (e.g., green tea extract, tauroursodeoxycholic acid&#xD;
             [TUDCA]/ursodiol), within 14 days, or 90 days for patisiran and 180 days for inotersen&#xD;
             prior to dosing. Prior to screening, tafamidis, if already prescribed to potential&#xD;
             subjects as part of their established background therapy, is allowed at the labeled&#xD;
             dosage and administration of 20 mg/day for the treatment of ATTR-PN with, i in the&#xD;
             opinion of the Investigator, evidence of disease progression while on tafamidis&#xD;
             treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark McGovern, RN, CCRN</last_name>
    <role>Study Director</role>
    <affiliation>Eidos Therapeutics, a BridgeBio company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eidos Therapeutics</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
    <country>Spain</country>
  </removed_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>June 11, 2021</last_update_submitted>
  <last_update_submitted_qc>June 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TTR</keyword>
  <keyword>ATTR-PN</keyword>
  <keyword>Familial ATTR-PN</keyword>
  <keyword>Amyloidosis</keyword>
  <keyword>Amyloid</keyword>
  <keyword>Transthyretin</keyword>
  <keyword>Polyneuropathy</keyword>
  <keyword>TTR-mediated amyloidosis</keyword>
  <keyword>Amyloidosis, hereditary</keyword>
  <keyword>Familial Amyloid Polyneuropathies</keyword>
  <keyword>Amyloidosis, Hereditary, Transthyretin-Related</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Amyloid Neuropathies</mesh_term>
    <mesh_term>Amyloid Neuropathies, Familial</mesh_term>
    <mesh_term>Amyloidosis</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/NCT04418024
org study id: AG10-333
secondary id: 2018-004670-10
nct id: NCT04418024
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with
      placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)
** See updated study design under ClinicalTrials.gov Identifier NCT04882735. **

      Transthyretin amyloid polyneuropathy (ATTR-PN), also called "Familial Transthyretin-Mediated
      Amyloid Polyneuropathy (FAP)" is a hereditary condition caused by mutations in the TTR gene.
      It is estimated that around 10,000 people in the world are affected.

      In ATTR-PN, amyloid builds up in the nerves that detect temperature, pain, and touch.
      Patients with ATTR-PN can experience a loss of sensation, tingling, numbness, or pain in the
      hands and feet (also called peripheral neuropathy).

      In this study Eidos is researching the investigational drug AG10 800mg (2 tablets)
      administered orally twice a day. Through the study, Eidos wants to evaluate the efficacy and
      safety of AG10 in patients with ATTR-PN versus placebo.

      This is an 18 month, placebo-controlled study. This means that, during the 18 month study,
      investigators conducting the research and study participants will not know whether the study
      participant is receiving AG10 or placebo.

      The primary outcome of the study is the difference between AG10 and placebo groups in the
      Modified Neurologic Impairment Score +7 (mNIS+7) at 18 months of treatment versus baseline.

      At the end of 18 months, participants may be eligible to receive investigational AG10, and
      there is no placebo. This is called an "open label extension." This part of the study may
      help us better understand the safety related to taking AG10 over a longer period of time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment
time frame: 18 Months
description: Evaluate the difference between the AG10 and placebo groups in Modified Neuropathy Impairment which is a composite scale that asses,in part, muscle weakness, sensory loss, and decreased muscle stretch reflexes. It is calculated on a scale of 0 to 304 with higher scores indicating a worsening of the disease.
arm group label: AG10 800 mg
arm group type: Experimental
description: TTR stabilizer administered orally twice daily (BID)
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo administered orally twice daily (BID)
intervention type: Drug
intervention name: AG10
description: TTR stabilizer administered orally twice daily (BID)
arm group label: AG10 800 mg
other name: Oral AG10
intervention type: Drug
intervention name: Placebo
description: Non-active control
arm group label: Placebo
other name: Placebo Oral Tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Mark McGovern, RN, CCRN
role: Study Director
affiliation: Eidos Therapeutics, a BridgeBio company
facility: 
country: United States
country: Canada
country: Spain
responsible party type: Sponsor
mesh term: Polyneuropathies
mesh term: Amyloid Neuropathies
mesh term: Amyloid Neuropathies, Familial
mesh term: Amyloidosis