<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/NCT03797612</url>
  </required_header>
  <id_info>
    <org_study_id>ADYX-005</org_study_id>
    <nct_id>NCT03797612</nct_id>
  </id_info>
  <brief_title>Study to Evaluate a Preop Dose of Brivoligide Injection for Pain After Knee Replacement in Patients With High PCS Scores</brief_title>
  <official_title>A Phase 2 Randomized Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Single Intrathecal Preoperative Administration of Brivoligide Injection in Patients With a Pain Catastrophizing Scale Score ≥16 Undergoing Unilateral Total Knee Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adynxx, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adynxx, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, Phase 2, randomized, double-blind, placebo-controlled study to&#xD;
      evaluate the safety and efficacy of brivoligide injection administered intrathecally before&#xD;
      surgery in patients with a Pain Catastrophizing Scale (PCS) score ≥16 undergoing primary&#xD;
      unilateral total knee arthroplasty.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to evaluate the safety and postoperative pain reducing&#xD;
      efficacy of a single preoperative intrathecal administration of brivoligide injection in&#xD;
      patients with a Pain Catastrophizing Scale (PCS) score ≥16 undergoing unilateral total knee&#xD;
      arthroplasty.&#xD;
&#xD;
      Potential subjects will be prescreened for PCS scores of 16 or greater in advance;&#xD;
      pre-qualified patients will be invited to the investigative site for informed consent and&#xD;
      full screening within 30 days of randomization. Patients providing informed consent and&#xD;
      meeting all study eligibility criteria will be enrolled in the study on the day of surgery&#xD;
      (Day 1). Safety assessments will be performed through Day 28; efficacy assessments will be&#xD;
      conducted at the follow-up visits and daily via electronic diary by subjects through Day 42.&#xD;
      Follow up visits will occur on Days 7, 14, 21, 28, and 42.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study initiation delayed due to COVID 19&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2021</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">January 2022</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Numerical Rating Scale (NRS) Pain with Walking 15 Meters</measure>
    <time_frame>Day 7 to Day 28</time_frame>
    <description>Least squares mean pain rating (NRS) with walking during the 15-meter walk Day 7 to Day 28</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Scale (NRS) Pain at Rest</measure>
    <time_frame>Day 7 to Day 28</time_frame>
    <description>Least squares mean pain rating (NRS) at rest Day 7 to Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical Rating Scale (NRS) Pain with 90 Degrees Passive Knee Flexion</measure>
    <time_frame>Day 7 to Day 28</time_frame>
    <description>Least squares mean pain rating (NRS) with passive knee flexion to 90 degrees from Day 7 to Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Postoperative Opioid Use</measure>
    <time_frame>Postoperative through Day 42</time_frame>
    <description>Total use of postoperative opioid medications (morphine equivalents) to Day 42</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Numerical Rating Scale (NRS) Pain ≤ 3 for Worst Pain</measure>
    <time_frame>Postoperative through Day 42</time_frame>
    <description>Time to achieve NRS pain score ≤ 3 for worst pain</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Brivoligide Injection 660 mg/6 mL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to the active treatment group will receive a single 660 mg/6 mL intrathecal administration of brivoligide injection as a slow bolus injection just prior to administration of spinal anesthesia, via the same needle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo 6 mL</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to the placebo group will receive a single 6 mL intrathecal injection of placebo as a slow bolus injection just prior to administration of spinal anesthesia, via the same needle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brivoligide Injection 660 mg/6 mL</intervention_name>
    <description>Single preoperative intrathecal injection</description>
    <arm_group_label>Brivoligide Injection 660 mg/6 mL</arm_group_label>
    <other_name>AYX1 Injection 660 mg/6 mL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo 6 mL</intervention_name>
    <description>Single preoperative intrathecal injection</description>
    <arm_group_label>Placebo 6 mL</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Score of 16 or greater on the PCS scale&#xD;
&#xD;
          -  Scheduled for primary unilateral TKA with spinal anesthesia as the primary anesthetic&#xD;
             for painful osteoarthritis without congenital knee pathology&#xD;
&#xD;
          -  American Society of Anesthesiologists Physical Status Classification System ≤ 3&#xD;
&#xD;
          -  Medically stable for elective surgery with spinal anesthetic as determined by the&#xD;
             Investigator&#xD;
&#xD;
          -  Body mass index of 18-45 kg/m2&#xD;
&#xD;
          -  Stable medical regimen at least 1 week before randomization&#xD;
&#xD;
          -  Able to read and understand study instructions in English or Spanish, and willing to&#xD;
             comply with all study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Target knee &gt; 20 degrees valgus or varus deformity, evidence of significant bone loss&#xD;
             or ligamentous laxity, or existing major hardware that requires removal during TKA&#xD;
&#xD;
          -  Inflammatory arthridities (e.g., rheumatoid arthritis, lupus, ankylosing spondylitis,&#xD;
             psoriatic arthritis), with the exception of clinically stable/non-active gout&#xD;
&#xD;
          -  Undergoing concomitant surgical procedures or non-elective TKA, or contralateral knee&#xD;
             is likely to require TKA within 6 weeks (or would interfere with study assessments)&#xD;
&#xD;
          -  Use of cryoneurolysis (including Iovera) on the current operative knee region within 6&#xD;
             months prior to randomization and/or at any time through the duration of the study&#xD;
&#xD;
          -  Planned use of general anesthesia as the primary anesthetic; planned use of neuroaxial&#xD;
             (intrathecal or epidural) opioids, or any use of extended release/long acting opioids&#xD;
             or ketamine preoperatively and/or at any time through the duration of the study&#xD;
&#xD;
          -  Use of more than 40 mg per day (on average) of oral morphine or its equivalent within&#xD;
             1 month prior to randomization&#xD;
&#xD;
          -  Current neurologic disorder, which could confound the assessment of pain (e.g.,&#xD;
             Parkinson's, Multiple Sclerosis)&#xD;
&#xD;
          -  Unstable mental condition and/or evidence of an uncooperative attitude in the opinion&#xD;
             of the Investigator; subjects diagnosed with schizophrenia, prescribed antipsychotic&#xD;
             medications or MAOIs&#xD;
&#xD;
          -  Women who are pregnant or nursing&#xD;
&#xD;
          -  Subjects engaged in pending or active litigation, or seeking disability compensation;&#xD;
             subjects whose cases have been settled or finally decided are not excluded&#xD;
&#xD;
          -  Participation in a clinical trial with the last dose or intervention within 1 month of&#xD;
             randomization, or planned participation in a clinical trial during this study&#xD;
&#xD;
          -  Previous participation in any study involving brivoligide injection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sheffield</city>
        <state>Alabama</state>
        <zip>35660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>January 6, 2019</study_first_submitted>
  <study_first_submitted_qc>January 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>July 9, 2020</last_update_submitted>
  <last_update_submitted_qc>July 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Knee replacement</keyword>
  <keyword>TKA</keyword>
  <keyword>Total Knee Arthroplasty</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will not be made available to other researchers.</ipd_description>
  </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/NCT03797612
org study id: ADYX-005
nct id: NCT03797612
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center, Phase 2, randomized, double-blind, placebo-controlled study to
      evaluate the safety and efficacy of brivoligide injection administered intrathecally before
      surgery in patients with a Pain Catastrophizing Scale (PCS) score ≥16 undergoing primary
      unilateral total knee arthroplasty.
The objective of this study is to evaluate the safety and postoperative pain reducing
      efficacy of a single preoperative intrathecal administration of brivoligide injection in
      patients with a Pain Catastrophizing Scale (PCS) score ≥16 undergoing unilateral total knee
      arthroplasty.

      Potential subjects will be prescreened for PCS scores of 16 or greater in advance;
      pre-qualified patients will be invited to the investigative site for informed consent and
      full screening within 30 days of randomization. Patients providing informed consent and
      meeting all study eligibility criteria will be enrolled in the study on the day of surgery
      (Day 1). Safety assessments will be performed through Day 28; efficacy assessments will be
      conducted at the follow-up visits and daily via electronic diary by subjects through Day 42.
      Follow up visits will occur on Days 7, 14, 21, 28, and 42.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Numerical Rating Scale (NRS) Pain with Walking 15 Meters
time frame: Day 7 to Day 28
description: Least squares mean pain rating (NRS) with walking during the 15-meter walk Day 7 to Day 28
measure: Numerical Rating Scale (NRS) Pain at Rest
time frame: Day 7 to Day 28
description: Least squares mean pain rating (NRS) at rest Day 7 to Day 28
measure: Numerical Rating Scale (NRS) Pain with 90 Degrees Passive Knee Flexion
time frame: Day 7 to Day 28
description: Least squares mean pain rating (NRS) with passive knee flexion to 90 degrees from Day 7 to Day 28
measure: Total Postoperative Opioid Use
time frame: Postoperative through Day 42
description: Total use of postoperative opioid medications (morphine equivalents) to Day 42
measure: Time to Numerical Rating Scale (NRS) Pain ≤ 3 for Worst Pain
time frame: Postoperative through Day 42
description: Time to achieve NRS pain score ≤ 3 for worst pain
arm group label: Brivoligide Injection 660 mg/6 mL
arm group type: Experimental
description: Subjects randomized to the active treatment group will receive a single 660 mg/6 mL intrathecal administration of brivoligide injection as a slow bolus injection just prior to administration of spinal anesthesia, via the same needle.
arm group label: Placebo 6 mL
arm group type: Placebo Comparator
description: Subjects randomized to the placebo group will receive a single 6 mL intrathecal injection of placebo as a slow bolus injection just prior to administration of spinal anesthesia, via the same needle.
intervention type: Drug
intervention name: Brivoligide Injection 660 mg/6 mL
description: Single preoperative intrathecal injection
arm group label: Brivoligide Injection 660 mg/6 mL
other name: AYX1 Injection 660 mg/6 mL
intervention type: Drug
intervention name: Placebo 6 mL
description: Single preoperative intrathecal injection
arm group label: Placebo 6 mL
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
sharing ipd: No
ipd description: Individual participant data will not be made available to other researchers.