<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/NCT03755934</url>
  </required_header>
  <id_info>
    <org_study_id>D5680C00002</org_study_id>
    <nct_id>NCT03755934</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of MEDI7352 in Subjects With Painful Diabetic Neuropathy</brief_title>
  <official_title>A Randomised, Double-Blind, Placebo-Controlled, Dose-Response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Diabetic Neuropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <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>
      This is a study investigating the effect of MEDI7352 on chronic pain in patients with painful&#xD;
      diabetic neuropathy.&#xD;
&#xD;
      The study incudes a screening period of up to 45 days and a 12-week treatment period during&#xD;
      which MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each&#xD;
      dose separated by 14 days. There will be a 6-week follow-up period.&#xD;
&#xD;
      Subjects will randomly be assigned to double-blind treatment with one of 4 dose levels of&#xD;
      MEDI7352 or placebo&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 19, 2018</start_date>
  <completion_date type="Actual">June 29, 2023</completion_date>
  <primary_completion_date type="Actual">June 29, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the weekly average of the average daily pain scores</measure>
    <time_frame>from the baseline week to Week 12</time_frame>
    <description>Change in the weekly average of the average daily pain scores from the baseline week to Week 12 of MEDI7352 compared to placebo, as measured on an 11-point (0-10) NRS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the weekly average of the average daily pain scores</measure>
    <time_frame>Weeks 2, 4, 6, 8, and 10 of treatment and the week before the follow-up visit (week 17).</time_frame>
    <description>Change in the weekly average of the average daily pain score, as measured on an 11-point (0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of treatment and the week before the follow-up visit (week 17).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the weekly average of the average daily pain scores</measure>
    <time_frame>from baseline during Weeks 4, 8, and 12 of treatment and the week before follow-up (week 17).</time_frame>
    <description>Percentage of subjects who have achieved ≥30% and ≥50% reductions in the weekly average of the average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week before follow-up (week 17).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Galer Neuropathic Pain Scale (NPS)</measure>
    <time_frame>from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18)</time_frame>
    <description>Change in Galer Neuropathic Pain Scale (NPS) from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Daily Sleep Interference Scale (DSIS)</measure>
    <time_frame>from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18)</time_frame>
    <description>Change in Daily Sleep Interference Scale (DSIS) from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who have 'improved', 'much improved,' or 'very much improved' relative to baseline on the Patient Global Impression of Change (PGIC)</measure>
    <time_frame>on Days 28, 56, and 84 of treatment and the follow-up visit (week 18).</time_frame>
    <description>Proportion of subjects who have 'improved', 'much improved,' or 'very much improved' relative to baseline on the Patient Global Impression of Change (PGIC) on Days 28, 56, and 84 of treatment and the follow-up visit (week 18).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the 36-item Short-Form Health Survey (SF-36)</measure>
    <time_frame>from baseline to Day 84 of treatment</time_frame>
    <description>Change in the 36-item Short-Form Health Survey (SF-36) from baseline to Day 84 of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the amount of rescue medication used (in terms of dosage/day)</measure>
    <time_frame>from baseline to Week 12 of treatment</time_frame>
    <description>Change in the amount of rescue medication used (in terms of dosage/day) from baseline to Week 12 of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of AEs and SAEs</measure>
    <time_frame>from baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve of MEDI7352</measure>
    <time_frame>from baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax) of MEDI7352</measure>
    <time_frame>from baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of positive ADA against MEDI7352</measure>
    <time_frame>from baseline up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To characterise the dose-response relationship of MEDI7352 on chronic pain in subjects with PDN</measure>
    <time_frame>from baseline up to 12 weeks</time_frame>
    <description>Change in the weekly average of the average daily pain scores from the baseline week to Week 12, as measured on an 11-point (0-10) NRS, versus dose.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">112</enrollment>
  <condition>Painful Diabetic Neuropathy</condition>
  <arm_group>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI7352</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI7352</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI7352</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI7352</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI7352</intervention_name>
    <description>MEDI7352</description>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_label>Dose Level 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion criteria:&#xD;
&#xD;
          -  Male, or postmenopausal or surgically sterile female, 18 to 80 years of age&#xD;
&#xD;
          -  Body mass index of ≤42 kg/m2.&#xD;
&#xD;
          -  Chronic PDN persistent for 6 months or longer, not adequately controlled by standard&#xD;
             of care treatments.&#xD;
&#xD;
          -  mean pain intensity score of ≥4, as measured on an 11-point (0-10) NRS&#xD;
&#xD;
          -  willing and able to discontinue all NSAID or COX-2 analgesic therapy&#xD;
&#xD;
          -  currently be taking medication for the treatment of PDN. Subjects should be taking at&#xD;
             least one of the first-line medications (consistent with regional or local standard of&#xD;
             care guidelines for PDN)&#xD;
&#xD;
        Key Exclusion criteria:&#xD;
&#xD;
          -  Presence of other clinically significant neuropathy (eg, hereditary neuropathy,&#xD;
             inflammatory neuropathy) or other clinically significant disorder (eg, nerve&#xD;
             compression injury) involving abnormal peripheral sensation, with an aetiology that is&#xD;
             considered to be distinct from that of PDN, and that is likely to interfere with&#xD;
             assessment of peripheral nerve function, as judged by the investigator.&#xD;
&#xD;
          -  History of osteonecrosis, rapidly progressing OA, subchondral insufficiency fractures,&#xD;
             neurogenic arthropathy, or analgesia-induced arthropathy.&#xD;
&#xD;
          -  Diagnosis of clinically significant OA currently affecting a major joint in the upper&#xD;
             extremity (shoulder, elbow, or wrist) or lower extremity (hip, knee, or ankle) or&#xD;
             axial spine; or other degenerative disease affecting any joint in subjects for whom,&#xD;
             in the opinion of the investigator, there is an identified risk of osteonecrosis,&#xD;
             rapidly progressing OA, subchondral insufficiency fractures, neurogenic arthropathy,&#xD;
             or analgesia-induced arthropathy.&#xD;
&#xD;
          -  Chronic pain condition, other than PDN, that is likely to interfere with the&#xD;
             evaluation of the subject's PDN pain, as judged by the investigator&#xD;
&#xD;
          -  Haemoglobin A1C greater than 8.5% (&gt;8.5%).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gentofte</city>
        <zip>2820</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Balatonfüred</city>
        <zip>8230</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Budapest</city>
        <zip>1036</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-065</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gdańsk</city>
        <zip>80-382</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Katowice</city>
        <zip>40-040</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Katowice</city>
        <zip>40-282</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kraków</city>
        <zip>30-534</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lublin</city>
        <zip>20-093</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lublin</city>
        <zip>20064</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Olsztyn</city>
        <zip>10117</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Poznań</city>
        <zip>60-702</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sochaczew</city>
        <zip>96-500</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toruń</city>
        <zip>87100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>01-192</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>01144</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wrocław</city>
        <zip>53-413</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bucuresti</city>
        <zip>011025</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Calarasi</city>
        <zip>917080</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Craiova</city>
        <zip>200505</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Galati</city>
        <zip>800291</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Targu-Mures</city>
        <zip>540142</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barnsley</city>
        <zip>S75 3DL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Blackpool</city>
        <zip>FY2 0JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cannock</city>
        <zip>WS11 0BN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leeds</city>
        <zip>LS10 1DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>NW10 7EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9NQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Prescot</city>
        <zip>L34 1BH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Stockton-on-Tees</city>
        <zip>TS17 6EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Hungary</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Spain</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>October 31, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</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>Diabetic Neuropathies</mesh_term>
    <mesh_term>Pain</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/NCT03755934
org study id: D5680C00002
nct id: NCT03755934
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a study investigating the effect of MEDI7352 on chronic pain in patients with painful
      diabetic neuropathy.

      The study incudes a screening period of up to 45 days and a 12-week treatment period during
      which MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each
      dose separated by 14 days. There will be a 6-week follow-up period.

      Subjects will randomly be assigned to double-blind treatment with one of 4 dose levels of
      MEDI7352 or placebo
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Double blind
measure: Change in the weekly average of the average daily pain scores
time frame: from the baseline week to Week 12
description: Change in the weekly average of the average daily pain scores from the baseline week to Week 12 of MEDI7352 compared to placebo, as measured on an 11-point (0-10) NRS.
measure: Change in the weekly average of the average daily pain scores
time frame: Weeks 2, 4, 6, 8, and 10 of treatment and the week before the follow-up visit (week 17).
description: Change in the weekly average of the average daily pain score, as measured on an 11-point (0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of treatment and the week before the follow-up visit (week 17).
measure: Change in the weekly average of the average daily pain scores
time frame: from baseline during Weeks 4, 8, and 12 of treatment and the week before follow-up (week 17).
description: Percentage of subjects who have achieved ≥30% and ≥50% reductions in the weekly average of the average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week before follow-up (week 17).
measure: Change in Galer Neuropathic Pain Scale (NPS)
time frame: from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18)
description: Change in Galer Neuropathic Pain Scale (NPS) from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18).
measure: Change in Daily Sleep Interference Scale (DSIS)
time frame: from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18)
description: Change in Daily Sleep Interference Scale (DSIS) from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18).
measure: Proportion of subjects who have 'improved', 'much improved,' or 'very much improved' relative to baseline on the Patient Global Impression of Change (PGIC)
time frame: on Days 28, 56, and 84 of treatment and the follow-up visit (week 18).
description: Proportion of subjects who have 'improved', 'much improved,' or 'very much improved' relative to baseline on the Patient Global Impression of Change (PGIC) on Days 28, 56, and 84 of treatment and the follow-up visit (week 18).
measure: Change in the 36-item Short-Form Health Survey (SF-36)
time frame: from baseline to Day 84 of treatment
description: Change in the 36-item Short-Form Health Survey (SF-36) from baseline to Day 84 of treatment.
measure: Change in the amount of rescue medication used (in terms of dosage/day)
time frame: from baseline to Week 12 of treatment
description: Change in the amount of rescue medication used (in terms of dosage/day) from baseline to Week 12 of treatment.
measure: incidence of AEs and SAEs
time frame: from baseline up to 18 weeks
measure: Area under the plasma concentration versus time curve of MEDI7352
time frame: from baseline up to 18 weeks
measure: Peak Plasma Concentration (Cmax) of MEDI7352
time frame: from baseline up to 18 weeks
measure: Summary of positive ADA against MEDI7352
time frame: from baseline up to 18 weeks
measure: To characterise the dose-response relationship of MEDI7352 on chronic pain in subjects with PDN
time frame: from baseline up to 12 weeks
description: Change in the weekly average of the average daily pain scores from the baseline week to Week 12, as measured on an 11-point (0-10) NRS, versus dose.
arm group label: Dose Level 1
arm group type: Experimental
description: MEDI7352
arm group label: Dose Level 2
arm group type: Experimental
description: MEDI7352
arm group label: Dose Level 3
arm group type: Experimental
description: MEDI7352
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
arm group label: Dose Level 4
arm group type: Experimental
description: MEDI7352
intervention type: Biological
intervention name: MEDI7352
description: MEDI7352
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
arm group label: Dose Level 4
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Hungary
country: Poland
country: Romania
country: United Kingdom
country: Spain
responsible party type: Sponsor
mesh term: Diabetic Neuropathies
mesh term: Pain