<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/NCT04466410</url>
  </required_header>
  <id_info>
    <org_study_id>XT-150-1-0102</org_study_id>
    <nct_id>NCT04466410</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of XT-150 for Treatment of Neuropathic Pain</brief_title>
  <official_title>A Double Blind, Placebo Controlled, Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Neuropathic 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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of&#xD;
      Neuropathic Pain. Intrathecally administered, single injection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      XT-150 has been safe and well tolerated in clinical studies of intra-articular knee&#xD;
      injections for osteoarthritis.&#xD;
&#xD;
      This is the initial study of XT-150 for treatment of neuropathic pain. For this indication&#xD;
      XT-150 must be administered by intrathecal injection. Doses used in the osteoarthritis&#xD;
      studies will be studied for neuropathic pain.&#xD;
&#xD;
      Upon safety reviews, doses will be increased by cohorts.&#xD;
&#xD;
      The study is placebo controlled and blinded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Failure to enroll a sufficient number of patients.&#xD;
  </why_stopped>
  <start_date type="Actual">April 14, 2021</start_date>
  <completion_date type="Actual">September 27, 2022</completion_date>
  <primary_completion_date type="Actual">September 27, 2022</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>Dose escalation by cohort following safety reviews</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Placebo and active drug are identical in appearance. Randomization will be provided to an unblinded pharmacist. Dosing and clinical assessments will be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Treatment-Emergent Adverse Events and Serious Adverse Events</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal vital signs</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant abnormal physical examination findings</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with anti-interleukin (IL)-10 antibodies</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with IL-10 Protein</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal clinical and hematology parameters</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with plasmid DNA present in whole blood</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with cytokines in Cerebrospinal fluid</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>0.015 milligram (mg) XT-150</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.015 mg of XT-150. Cohort 1 of the study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.15 mg XT-150</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.15 mg of XT-150. Cohort 2 of the study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.45 mg XT-150</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.45 mg of XT-150. Cohort 3 of the study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>PBS for injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>XT-150</intervention_name>
    <description>Single bolus intrathecal injection</description>
    <arm_group_label>0.015 milligram (mg) XT-150</arm_group_label>
    <arm_group_label>0.15 mg XT-150</arm_group_label>
    <arm_group_label>0.45 mg XT-150</arm_group_label>
    <other_name>IL-10 transgene plasmid DNA injected intrathecally</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo is a sterile phosphate-buffered saline</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form&#xD;
&#xD;
          2. Male or female, between 18 and 80 years of age, inclusive&#xD;
&#xD;
          3. Clinical indication: Lumbar disk disease with no prior lumbar surgery with radicular&#xD;
             pain symptoms and/or signs of compressive neuropathy&#xD;
&#xD;
          4. At screening and baseline, a pain intensity score &gt; 60 using the visual analog scale&#xD;
             of pain intensity [VASPI] (0-100 mm scale) and a participant reported history of pain&#xD;
             in the past 3 or more months&#xD;
&#xD;
          5. Medically stable as determined by the Principal Investigator in consultation with the&#xD;
             Sponsor's Medical Monitor, based on pre-study medical history, physical examination,&#xD;
             and clinical laboratory tests&#xD;
&#xD;
          6. In the judgment of the Principal Investigator, acceptable vital signs: blood pressure;&#xD;
             resting heart rate; respirations, and oral temperature&#xD;
&#xD;
          7. Life expectancy &gt;6 months as determined by the Principal Investigator&#xD;
&#xD;
          8. Female participants of child-bearing potential, and those &lt;1 year post-menopausal,&#xD;
             must be practicing highly effective methods of birth control such as hormonal methods&#xD;
             (e.g., combined oral, implantable, injectable, or transdermal contraceptives), double&#xD;
             barrier methods (e.g., condoms, sponge, diaphragm, or vaginal ring plus spermicidal&#xD;
             jellies or cream), or total abstinence from heterosexual intercourse for a minimum of&#xD;
             1 full menstruation cycle before study drug administration and agree to continue&#xD;
             abstinence for 1 full menstruation cycle after the study is completed&#xD;
&#xD;
          9. Male participants who are heterosexually active, and not surgically sterile, must&#xD;
             agree to use effective contraception for the duration of the study and for 1 month&#xD;
             after the study is completed&#xD;
&#xD;
         10. Stable medical regimen for ≥1 month before screening assessments&#xD;
&#xD;
         11. Have suitable lumbar anatomy for intrathecal injection as determined by MRI or X-Ray&#xD;
             in the last 6 months.&#xD;
&#xD;
         12. Willing and able to return for the follow-up (FU) visits&#xD;
&#xD;
         13. Able to read and understand study instructions, and willing and able to comply with&#xD;
             all study procedures&#xD;
&#xD;
         14. Adequately informed of the nature and risks of the study and give written informed&#xD;
             consent before receiving any study specific assessments or procedures&#xD;
&#xD;
         15. Stable use of non-prescription pain therapy, including massage, TENS, physiotherapy&#xD;
             osteopathy, chiropractic and acupuncture for 2 months prior and throughout the study&#xD;
             period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants must NOT meet any of the following exclusion criteria:&#xD;
&#xD;
          1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug&#xD;
&#xD;
          2. Any spinal deformity preventing intrathecal injection or making intrathecal injection&#xD;
             unsafe&#xD;
&#xD;
          3. Prior history of lumbar surgery, including fusion and microdiscectomy&#xD;
&#xD;
          4. History of epidural block or facet block or steroid injection in the last 6 months&#xD;
&#xD;
          5. Current unstable angina, uncontrolled congestive heart failure, or &gt;1+ pitting edema&#xD;
             of lower extremities&#xD;
&#xD;
          6. History of acute myocardial infarction, transient ischemic attack, stroke, or seizure&#xD;
             within 3 months of screening visit&#xD;
&#xD;
          7. Severe chronic obstructive or restrictive pulmonary disease&#xD;
&#xD;
          8. Current insulin dependent diabetes mellitus&#xD;
&#xD;
          9. Current autoimmune conditions or documented immunodeficiency&#xD;
&#xD;
         10. History of immunosuppressive therapy; high-potency systemic steroids in the last 3&#xD;
             months&#xD;
&#xD;
         11. Current treatment with systemic immunosuppressive (systemic corticosteroid therapy&#xD;
             [equivalent to &gt;10mg/day prednisone] or other strong immunosuppressant)&#xD;
&#xD;
         12. Current or history of central nervous system cancer&#xD;
&#xD;
         13. Any malignancy (EXCEPTION: localized non-melanoma skin cancers) within 5 years before&#xD;
             the screening visit or currently receiving systemic chemotherapy, radiation therapy,&#xD;
             or a surgical stabilization procedure&#xD;
&#xD;
         14. Significant hepatic disease as indicated by clinical laboratory results for the&#xD;
             following: ≥3 times the upper limit of normal (ULN) for aspartate aminotransferase,&#xD;
             alanine aminotransferase, ≥ 2.5 time ULN alkaline phosphatase, or ≥1.5 times ULN for&#xD;
             total bilirubin)&#xD;
&#xD;
         15. Severe anemia (Grade 3; hemoglobin &lt;8.0 g/dL, &lt;4.9 mmol/L, &lt;80 g/L; transfusion&#xD;
             indicated), Grade 1 white cell counts (lymphocytes &lt;LLN - 800/mm3; &lt;LLN - 0.8 x 109&#xD;
             /L, neutrophils &lt;LLN - 1500/mm3; &lt;LLN - 1.5 x 109 /L)&#xD;
&#xD;
         16. Significant renal disease as indicated by creatinine ≥1.5 times the upper limit of&#xD;
             normal or creatinine clearance &lt;80 mL/minute (Cockcroft-Gault formula estimate)&#xD;
&#xD;
         17. Confirmed positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C&#xD;
             virus&#xD;
&#xD;
         18. Significant psychological conditions; dementia, major depression, or altered mental&#xD;
             state that in the opinion of the Investigator will interfere with study participation&#xD;
&#xD;
         19. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical&#xD;
             treatments)&#xD;
&#xD;
         20. Current treatment with anticoagulants /antiplatelet medications except for low dose&#xD;
             aspirin or low dose aspirin-containing compounds. Participants, if medically feasible,&#xD;
             can interrupt anticoagulant therapy by following local medical practice protocol for&#xD;
             intrathecal injections for participants on anticoagulant, antiplatelet therapy.&#xD;
&#xD;
         21. Current use of systemic corticosteroids (equivalent to &gt;10mg/day prednisone)&#xD;
&#xD;
         22. Known or suspected history of active alcohol or illicit drug abuse within 1 year&#xD;
             before the screening visit&#xD;
&#xD;
         23. Women who are pregnant or nursing&#xD;
&#xD;
         24. Use of any investigational drug or device within 1 month before randomization or&#xD;
             current 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;
         25. Any condition that, in the opinion of the Principal Investigator, could compromise the&#xD;
             safety of the participants, the participant's ability to communicate the study staff,&#xD;
             or the quality of the data&#xD;
&#xD;
         26. Presence of an implanted intrathecal infusion system or peripheral neurostimulator&#xD;
&#xD;
         27. Presence of a generalized pain disorder such as fibromyalgia or complex regional pain&#xD;
             syndrome that in the opinion of the PI may impact on evaluation of response to the&#xD;
             study drug&#xD;
&#xD;
         28. Diagnosis of peripheral neuropathy of the lower extremities which in the opinion of&#xD;
             the PI, might interfere with the participant's ability to assess the effect of the&#xD;
             study drug on the radicular signs and/or symptoms&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Howard Rutman, MD,MBA</last_name>
    <role>Study Director</role>
    <affiliation>Xalud Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Genesis Research Services</name>
      <address>
        <city>Newcastle</city>
        <state>New South Wales</state>
        <zip>2292</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CerCare</name>
      <address>
        <city>Wayville</city>
        <state>South Australia</state>
        <zip>5034</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metro Pain Group</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>January 19, 2023</last_update_submitted>
  <last_update_submitted_qc>January 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>XT-150</keyword>
  <keyword>Plasmid Gene Therapy</keyword>
  <keyword>IL-10</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04466410
org study id: XT-150-1-0102
nct id: NCT04466410
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of
      Neuropathic Pain. Intrathecally administered, single injection.
XT-150 has been safe and well tolerated in clinical studies of intra-articular knee
      injections for osteoarthritis.

      This is the initial study of XT-150 for treatment of neuropathic pain. For this indication
      XT-150 must be administered by intrathecal injection. Doses used in the osteoarthritis
      studies will be studied for neuropathic pain.

      Upon safety reviews, doses will be increased by cohorts.

      The study is placebo controlled and blinded.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Dose escalation by cohort following safety reviews
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Placebo and active drug are identical in appearance. Randomization will be provided to an unblinded pharmacist. Dosing and clinical assessments will be blinded.
measure: Number of participants with Treatment-Emergent Adverse Events and Serious Adverse Events
time frame: 6 months
measure: Number of participants with abnormal vital signs
time frame: 6 months
measure: Number of participants with clinically significant abnormal physical examination findings
time frame: 6 months
measure: Number of participants with anti-interleukin (IL)-10 antibodies
time frame: 6 months
measure: Number of participants with IL-10 Protein
time frame: 6 months
measure: Number of participants with abnormal clinical and hematology parameters
time frame: 6 months
measure: Number of participants with plasmid DNA present in whole blood
time frame: 6 months
measure: Number of participants with cytokines in Cerebrospinal fluid
time frame: 6 months
arm group label: 0.015 milligram (mg) XT-150
arm group type: Experimental
description: 0.015 mg of XT-150. Cohort 1 of the study
arm group label: 0.15 mg XT-150
arm group type: Experimental
description: 0.15 mg of XT-150. Cohort 2 of the study
arm group label: 0.45 mg XT-150
arm group type: Experimental
description: 0.45 mg of XT-150. Cohort 3 of the study
arm group label: Placebo
arm group type: Placebo Comparator
description: PBS for injection.
intervention type: Biological
intervention name: XT-150
description: Single bolus intrathecal injection
arm group label: 0.015 milligram (mg) XT-150
arm group label: 0.15 mg XT-150
arm group label: 0.45 mg XT-150
other name: IL-10 transgene plasmid DNA injected intrathecally
intervention type: Biological
intervention name: Placebo
description: Placebo is a sterile phosphate-buffered saline
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Howard Rutman, MD,MBA
role: Study Director
affiliation: Xalud Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Neuralgia
sharing ipd: No