<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/NCT03282149</url>
  </required_header>
  <id_info>
    <org_study_id>XT-150-1-0201</org_study_id>
    <nct_id>NCT03282149</nct_id>
  </id_info>
  <brief_title>Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain</brief_title>
  <official_title>A Placebo-controlled, Preliminary Evaluation of Safety, Tolerability, and Efficacy of Ascending Doses of XT-150 for the Treatment of Osteoarthritic Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xalud Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xalud Therapeutics, 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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of&#xD;
      Osteoarthritic Pain - Dose escalation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of&#xD;
      Osteoarthritic Pain.&#xD;
&#xD;
      Subjects for whom replacement knee surgery is recommended will be enrolled in the study. A&#xD;
      single injection of a DNA plasmid with a variant Interleukin-10 (IL-10) transgene will be&#xD;
      injected into the synovial capsule of the knee.&#xD;
&#xD;
      This is a first in human, dose-range, safety and efficacy study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 21, 2018</start_date>
  <completion_date type="Actual">June 15, 2019</completion_date>
  <primary_completion_date type="Actual">March 31, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Inflammation and pain due to osteoarthritis in the knee</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Unblinded pharmacy provides injection preparation for blinded administration</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety]</measure>
    <time_frame>180 days post treatment</time_frame>
    <description>Clinical Pathology, Adverse Events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Verbal Numerical Rating Scale</measure>
    <time_frame>180 days post treatment</time_frame>
    <description>0 - 10 Pain assessment</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <arm_group>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lowest trial dose of XT-150</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Second, escalating dose of XT-150</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Third, escalating dose of XT-150</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>2 of 8 participants in each cohort will randomly be assigned to placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>XT-150</intervention_name>
    <description>IL-10 transgene DNA plasmid injected into the knee synovial capsule</description>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_label>Dose 3</arm_group_label>
    <arm_group_label>Saline placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, between 18 and 90 years of age, inclusive. Women who are not of&#xD;
             child-bearing potential in the same age range.&#xD;
&#xD;
          2. Sufficiently severe OA of knee to require/have recommended knee replacement surgery or&#xD;
             be unsuitable for knee replacement surgery or be unsuitable for knee replacement&#xD;
             surgery based on co-morbidities or orthopedic considerations; be free of local or&#xD;
             intra-articular infection.&#xD;
&#xD;
          3. Symptomatic disease because of osteoarthritis, defined as one or more of the following&#xD;
             Verbal Numerical Rating Scale (VNRS) scores:&#xD;
&#xD;
               1. a worst pain of at least 7 at any time during the preceding week (based on scale&#xD;
                  of 0 to 10, with 10 representing &quot;pain as bad as you can imagine&quot;).&#xD;
&#xD;
               2. a worst stiffness of at least 7 at any time during the preceding week (based on a&#xD;
                  scale of 0 to 10, with 10 representing &quot;stiffness as bad as you can imagine&quot;).&#xD;
&#xD;
          4. Stable analgesic regimen during the 4 weeks prior to enrollment.&#xD;
&#xD;
          5. Inadequate pain relief (mean &gt;5 mean on Brief Pain Inventory-Severity Scale) from&#xD;
             prior therapies lasting 3 months.&#xD;
&#xD;
          6. In the judgment of the Investigator, acceptable general medical condition&#xD;
&#xD;
          7. Life expectancy &gt;6 months&#xD;
&#xD;
          8. Male participants who are heterosexually active and not surgically sterile must agree&#xD;
             to use effective contraception, including abstinence, for the duration of the study&#xD;
             and for 3 months after the study is completed.&#xD;
&#xD;
          9. Have suitable knee joint anatomy for intra-articular injection&#xD;
&#xD;
         10. Willing and able to return for the follow-up (FU) visits&#xD;
&#xD;
         11. Able to reliably provide pain assessment&#xD;
&#xD;
         12. Able to read and understand study instructions, and willing and able to comply with&#xD;
             all study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study&#xD;
             drug, including double-stranded DNA, mannose, and sucrose&#xD;
&#xD;
          2. Scheduled knee replacement within 4 months; participant agrees not to schedule a knee&#xD;
             replacement appointment within 4 months of study treatment&#xD;
&#xD;
          3. History of rheumatoid arthritis of the knee&#xD;
&#xD;
          4. High peri-operative risks which in the judgment of the investigator preclude a safe&#xD;
             knee injection procedure (e.g., poorly controlled diabetes, cardiac inadequacy such as&#xD;
             NYHA class &gt; II, G4 glomerular filtration rate [eGFR &lt; 30 mL/min by Cockcroft-Gault])&#xD;
&#xD;
          5. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent&#xD;
             to &gt;10mg/day prednisone] or other strong immunosuppressant)&#xD;
&#xD;
          6. History of immunosuppressive therapy; high-potency systemic steroids in the last 3&#xD;
             months.&#xD;
&#xD;
          7. Currently receiving systemic chemotherapy or radiation therapy for malignancy&#xD;
&#xD;
          8. Clinically significant hepatic disease as indicated by clinical laboratory results ≥3&#xD;
             times the upper limit of normal for any liver function test (e.g., aspartate&#xD;
             aminotransferase, alanine aminotransferase, lactate dehydrogenase)&#xD;
&#xD;
          9. Severe anemia (Grade 3; hemoglobin &lt;8.0 g/dL, &lt;4.9 mmol/L, &lt;80 g/L; transfusion&#xD;
             indicated), uncontrolled coagulopathy (Grade 1, prolonged activated partial&#xD;
             prothrombin time (aPTT) &gt; upper limit of normal (ULN) to 1.5xULN), or bleeding&#xD;
             diathesis, Grade 1 white cell counts (lymphocytes &lt;LLN - 800/mm3; &lt;LLN - 0.8 x 10e9&#xD;
             /L, neutrophils &lt;LLN - 1500/mm3; &lt;LLN - 1.5 x 10e9 /L)&#xD;
&#xD;
         10. Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C&#xD;
             virus within 4 weeks of commencing the study&#xD;
&#xD;
         11. Significant neuropsychiatric conditions; dementia, major depression, or altered mental&#xD;
             state that in the opinion of the Investigator will interfere with study participation&#xD;
&#xD;
         12. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical&#xD;
             treatments)&#xD;
&#xD;
         13. Current treatment with anticoagulants, other than low-dose aspirin, prescribed for new&#xD;
             onset of symptoms in 3 months before screening visit.&#xD;
&#xD;
         14. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1&#xD;
             year before the screening visit&#xD;
&#xD;
         15. Women of child-bearing potential&#xD;
&#xD;
         16. Use of any investigational drug or device within 1 month before enrollment or current&#xD;
             participation in a trial that included intervention with a drug or device; or&#xD;
             currently participating in an investigational drug or device study.&#xD;
&#xD;
         17. Any condition that, in the opinion of the Principal Investigator, could compromise the&#xD;
             safety of the participant, the participant's ability to communicate the study staff,&#xD;
             or the quality of the data&#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 Rickman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Adelaide</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CMAX Clinical Research Pty Ltd in collaboration with University of Adelaide</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5005</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>July 2, 2019</last_update_submitted>
  <last_update_submitted_qc>July 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>inflammation</keyword>
  <keyword>cytokine</keyword>
  <keyword>anti-inflammatory</keyword>
  <keyword>pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All data will be de-identified in a clinical trial database</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/NCT03282149
org study id: XT-150-1-0201
nct id: NCT03282149
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of
      Osteoarthritic Pain - Dose escalation
Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of
      Osteoarthritic Pain.

      Subjects for whom replacement knee surgery is recommended will be enrolled in the study. A
      single injection of a DNA plasmid with a variant Interleukin-10 (IL-10) transgene will be
      injected into the synovial capsule of the knee.

      This is a first in human, dose-range, safety and efficacy study.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Inflammation and pain due to osteoarthritis in the knee
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Unblinded pharmacy provides injection preparation for blinded administration
measure: Incidence of Treatment-Emergent Adverse Events [Safety]
time frame: 180 days post treatment
description: Clinical Pathology, Adverse Events
measure: Verbal Numerical Rating Scale
time frame: 180 days post treatment
description: 0 - 10 Pain assessment
arm group label: Dose 1
arm group type: Experimental
description: Lowest trial dose of XT-150
arm group label: Dose 2
arm group type: Experimental
description: Second, escalating dose of XT-150
arm group label: Dose 3
arm group type: Experimental
description: Third, escalating dose of XT-150
arm group label: Saline placebo
arm group type: Placebo Comparator
description: 2 of 8 participants in each cohort will randomly be assigned to placebo
intervention type: Biological
intervention name: XT-150
description: IL-10 transgene DNA plasmid injected into the knee synovial capsule
arm group label: Dose 1
arm group label: Dose 2
arm group label: Dose 3
arm group label: Saline placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Mark Rickman, MD
role: Principal Investigator
affiliation: University of Adelaide
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Osteoarthritis, Knee
sharing ipd: No
ipd description: All data will be de-identified in a clinical trial database