<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/NCT03263611</url>
  </required_header>
  <id_info>
    <org_study_id>AMG0103-US-01</org_study_id>
    <nct_id>NCT03263611</nct_id>
  </id_info>
  <brief_title>AMG0103 in Subjects With Chronic Discogenic Lumbar Back Pain</brief_title>
  <official_title>A Phase 1b, Multicenter, Double-blind, Randomized, Placebo-controlled, Single Ascending-Dose, Clinical Study Evaluating the Safety, Tolerability and Exploratory Efficacy of a Targeted Single Injection of an Intradiscal Nuclear Factor-κB Decoy Oligodeoxynucleotide (AMG0103) in Subjects With Chronic Discogenic Lumbar Back Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AnGes, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AnGes, Inc.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial evaluate the safety, tolerability and exploratory efficacy of targeted&#xD;
      single injection of AMG0103 in subject with chronic discogenic lumbar back pain&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1b, multicenter, double-blind, single ascending dose study designed to&#xD;
      evaluate the safety of AMG0103 in adult male and female subjects with chronic discogenic&#xD;
      lumbar back pain.&#xD;
&#xD;
      This protocol anticipates that 8 subjects with symptomatic single level discogenic pain will&#xD;
      be enrolled in each of up to 3 dose-escalation cohorts. Subjects in each cohort will receive&#xD;
      AMG0103 or Placebo as a targeted, single, intradiscal injection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 26, 2018</start_date>
  <completion_date type="Actual">February 15, 2021</completion_date>
  <primary_completion_date type="Actual">February 15, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: treatment-emergent adverse events (AEs)</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety: data from 12-lead electrocardiograms</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety: data from clinical laboratory evaluations (hematology, serum chemistry, coagulation, inflammation and immunology)</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Analogue Scale (VAS) for pain</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oswestry Disability Index to assess Activity of Daily Living</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Roland Morris Disability Questionnaire to assess Activity of Daily Living</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impression of Change pain self-assessment scale to assess Quality of Life</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SF-36 to assess Quality of Life</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disc space height by X-ray</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pfirrmann Score by MRI</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of AMG0103: Cmax</measure>
    <time_frame>1 month</time_frame>
    <description>Maximum plasma concentration estimate for a single injection of AMG0103</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of AMG0103: Tmax</measure>
    <time_frame>1 month</time_frame>
    <description>Time to maximum plasma concentration estimate for a single injection of AMG0103</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK of AMG0103: AUC</measure>
    <time_frame>1 month</time_frame>
    <description>Area under the plasma-concentration time curve (AUC) estimate for a single injection of AMG0103</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of AMG0103 excreted into urine</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Degenerative Disc Disease</condition>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>subject will receive single intradiscal injection of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AMG0103 low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subject will receive single intradiscal injection of AMG0103 low dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AMG0103 middle dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subject will receive single intradiscal injection of AMG0103 middle dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AMG0103 high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subject will receive single intradiscal injection of AMG0103 high dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>single intradiscal injection</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMG0103</intervention_name>
    <description>single intradiscal injection</description>
    <arm_group_label>AMG0103 high dose</arm_group_label>
    <arm_group_label>AMG0103 low dose</arm_group_label>
    <arm_group_label>AMG0103 middle dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, between 18 and 75 years of age, inclusive, and skeletally mature, in&#xD;
             the opinion of the investigator.&#xD;
&#xD;
          2. Has provided written informed consent before undergoing any study-specific procedures.&#xD;
&#xD;
          3. Has chronic low back pain for at least 6 months, where back pain is greater than leg&#xD;
             pain.&#xD;
&#xD;
          4. Has separate low back pain and leg pain VAS scores within the following parameters:&#xD;
&#xD;
               1. Average low back pain VAS score of at least 40 mm and less than 90 mm on a 100 mm&#xD;
                  visual analog scale.&#xD;
&#xD;
               2. Average leg pain VAS score that is less than or equal to 50% of the average low&#xD;
                  back pain VAS score above, where leg pain VAS scores are measured on a 100 mm&#xD;
                  visual analog scale.&#xD;
&#xD;
          5. Has had inadequate response to conservative medical care over a period of at least 3&#xD;
             months.&#xD;
&#xD;
          6. Diagnosis of painful degenerative disc disease at one lumbar level from L1 to S1&#xD;
             confirmed by subject history and radiographic studies (eg, MRI, x-rays). Radiographic&#xD;
             studies must demonstrate the following:&#xD;
&#xD;
               1. A Pfirrmann score of 3 or 4 on MRI in just a single disc between L1 and S1&#xD;
&#xD;
               2. With or without contained disc herniations of &lt;3 mm protrusion with no&#xD;
                  radiographic evidence of neurologic compression&#xD;
&#xD;
               3. Disc height loss of the symptomatic disc is less than 50% of the adjacent discs&#xD;
&#xD;
               4. All discs other than the index disc must have a Pfirrman score of less than 3&#xD;
&#xD;
               5. No spondylolisthesis or instability on flexion/extension views of more than 1-2&#xD;
                  mm&#xD;
&#xD;
               6. No evidence of sacroiliac, or extra-spinal, pathology that could account for&#xD;
                  lumbar back pain&#xD;
&#xD;
               7. No more fluid in, or widening of, the facet joints around the symptomatic disc&#xD;
                  than is seen on the other facet joints of &quot;normal&quot; levels&#xD;
&#xD;
          7. Has a Body Mass Index (BMI) between 15.0 and 35.0 kg/m2 at the screening visit.&#xD;
&#xD;
          8. Oswestry Disability Index score of at least 30 and not more than 90 on the 100 point&#xD;
             questionnaire.&#xD;
&#xD;
          9. Willing and able to comply with all protocol requirements.&#xD;
&#xD;
         10. Females of childbearing potential must agree to use highly effective methods of&#xD;
             contraception during heterosexual intercourse from the date they sign the ICF until 1&#xD;
             year after the single dose of study drug is administered.&#xD;
&#xD;
         11. Male subjects must agree that, if their partner is of childbearing potential, they and&#xD;
             the partner will use an appropriate method of contraception as defined above.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has any prior or current medical condition (eg, an active systemic infection),&#xD;
             including known bleeding disorders that, in the judgment of the Investigator, would&#xD;
             prevent the subject from safely participating in and/or completing all study&#xD;
             requirements.&#xD;
&#xD;
          2. Has any clinically significant finding on a screening evaluation that in the judgment&#xD;
             of the Investigator would preclude safe study completion.&#xD;
&#xD;
          3. Liver function tests &gt;1.5 the upper limit of normal (ULN) for alkaline phosphatase,&#xD;
             alanine aminotransferase (ALT), aspartate aminotransferase (AST)&#xD;
&#xD;
          4. Serum creatinine &gt;1.5 ULN at screening&#xD;
&#xD;
          5. Blood pressure &gt;160/110 mm Hg recorded on 3 readings at screening and/or resting pulse&#xD;
             &gt;120 beats/min at screening&#xD;
&#xD;
          6. Body temperature ≥101°F on day of planned injection&#xD;
&#xD;
          7. Has a co-morbid medical condition of the spine or the upper extremities that may&#xD;
             affect neurological and/or pain assessments as specified in the protocol, including&#xD;
             spinal fusion, spondylolysis and spondylolisthesis.&#xD;
&#xD;
          8. Has evidence of hip pathology based on clinical history, physical exam and/or&#xD;
             radiographic imaging that could be the source of lumbar back pain.&#xD;
&#xD;
          9. Has a history of an endocrine or metabolic disorder that affects the spine (eg,&#xD;
             Paget's disease).&#xD;
&#xD;
         10. Has a compressive pathology due to stenosis or frankly herniated disc or sequestered&#xD;
             discs.&#xD;
&#xD;
         11. Has symptomatic involvement of more than one lumbar disc, in the opinion of the&#xD;
             investigator.&#xD;
&#xD;
         12. Has an intact disc bulge/protrusion or focal herniation at the symptomatic level &gt;3&#xD;
             mm, the presence of disc extrusion or sequestration, or a complete annular tear.&#xD;
&#xD;
         13. Has lumbar intervertebral foraminal stenosis at the symptomatic level resulting in&#xD;
             clinically significant spinal nerve root compression, in the opinion of the&#xD;
             investigator.&#xD;
&#xD;
         14. Has undergone a previous surgery at the symptomatic disc, or has plans to do so within&#xD;
             6 months of receiving the dose of AMG0103, that has altered the structure of the&#xD;
             target disc level, or is likely to do so (eg, laminectomy, foraminotomy, fusion,&#xD;
             intradiscal electrothermal therapy, intradiscal radiofrequency, thermocoagulation).&#xD;
&#xD;
         15. Has had any lumbar intradiscal injection procedure (eg, injection of corticosteroids,&#xD;
             methylene blue, dextrose, or glucosamine and chondroitin sulfate). Discography may be&#xD;
             performed, but must be done at least 3 weeks (or more) prior to the injection&#xD;
             procedure in this study.&#xD;
&#xD;
         16. Has had any epidural steroid injection(s) within 3 months prior to study treatment.&#xD;
&#xD;
         17. Is a female who is pregnant, planning to become pregnant, or lactating.&#xD;
&#xD;
         18. Has a PT(INR) and/or aPTT lab result outside of the reference range, or within the&#xD;
             last 30 days taken, or is currently on, an anticoagulant therapy (e.g., Warfarin) for&#xD;
             the purpose of treating or preventing blood clots.&#xD;
&#xD;
         19. Has ferromagnetic implants that would disallow MRI of the symptomatic disc.&#xD;
&#xD;
         20. Is involved in current or pending spinal litigation where permanent disability&#xD;
             benefits are being sought.&#xD;
&#xD;
         21. Has a physical or mental condition (eg, senile dementia, Alzheimer's disease) that&#xD;
             would interfere with Subject self-assessment of function, pain or quality of life.&#xD;
&#xD;
         22. Has a positive screen for Hepatitis B Surface Antigen, Hepatitis C antibodies, or&#xD;
             human immunodeficiency virus (HIV) by antibodies or nucleic acid test.&#xD;
&#xD;
         23. Is an immediate family member (by birth) of any other subject participating in this&#xD;
             study.&#xD;
&#xD;
         24. Has a history of cancer that does NOT have documentation to support a complete and&#xD;
             curative treatment.&#xD;
&#xD;
         25. Has participated within the previous 3 months in an interventional clinical study or&#xD;
             is concurrently enrolled in any non-interventional research of any type judged to be&#xD;
             scientifically or medically incompatible with this study.&#xD;
&#xD;
         26. Is transient or has been treated in the 6 months prior to providing informed consent&#xD;
             for alcohol and/or drug abuse in an inpatient substance abuse program.&#xD;
&#xD;
         27. Is currently incarcerated (a prisoner).&#xD;
&#xD;
         28. Is an Investigator-site employee or immediate family (defined as a spouse, parent,&#xD;
             child, or sibling, whether biological or legally adopted) of an Investigator-site&#xD;
             employee.&#xD;
&#xD;
         29. Is a Sponsor employee (permanent, temporary contract worker, or designee responsible&#xD;
             for the conduct of the study) or immediate family (defined as a spouse, parent, child,&#xD;
             or sibling, whether biological or legally adopted) of a Sponsor employee.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>AnGes, Inc. Clinical Development</last_name>
    <role>Study Director</role>
    <affiliation>AnGes, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Keck Medicine of USC</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spine Institute of San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Medical Pain Management</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Medical Relief</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>October 8, 2021</last_update_submitted>
  <last_update_submitted_qc>October 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>disc degeneration</keyword>
  <keyword>Intervertebral disc</keyword>
  <keyword>discogenic pain</keyword>
  <keyword>chronic discogenic lumbar back pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intervertebral Disc Degeneration</mesh_term>
    <mesh_term>Back Pain</mesh_term>
    <mesh_term>Low Back Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
  </patient_data>
  <pending_results>
    <submitted>November 30, 2022</submitted>
  </pending_results>
  <!-- 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/NCT03263611
org study id: AMG0103-US-01
nct id: NCT03263611
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This clinical trial evaluate the safety, tolerability and exploratory efficacy of targeted
      single injection of AMG0103 in subject with chronic discogenic lumbar back pain
This is a Phase 1b, multicenter, double-blind, single ascending dose study designed to
      evaluate the safety of AMG0103 in adult male and female subjects with chronic discogenic
      lumbar back pain.

      This protocol anticipates that 8 subjects with symptomatic single level discogenic pain will
      be enrolled in each of up to 3 dose-escalation cohorts. Subjects in each cohort will receive
      AMG0103 or Placebo as a targeted, single, intradiscal injection.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety: treatment-emergent adverse events (AEs)
time frame: 6 months
measure: Safety: data from 12-lead electrocardiograms
time frame: 6 months
measure: Safety: data from clinical laboratory evaluations (hematology, serum chemistry, coagulation, inflammation and immunology)
time frame: 6 months
measure: Visual Analogue Scale (VAS) for pain
time frame: 6 months
measure: Oswestry Disability Index to assess Activity of Daily Living
time frame: 6 months
measure: Roland Morris Disability Questionnaire to assess Activity of Daily Living
time frame: 6 months
measure: Patient Global Impression of Change pain self-assessment scale to assess Quality of Life
time frame: 6 months
measure: SF-36 to assess Quality of Life
time frame: 6 months
measure: Disc space height by X-ray
time frame: 6 months
measure: Pfirrmann Score by MRI
time frame: 6 months
measure: PK of AMG0103: Cmax
time frame: 1 month
description: Maximum plasma concentration estimate for a single injection of AMG0103
measure: PK of AMG0103: Tmax
time frame: 1 month
description: Time to maximum plasma concentration estimate for a single injection of AMG0103
measure: PK of AMG0103: AUC
time frame: 1 month
description: Area under the plasma-concentration time curve (AUC) estimate for a single injection of AMG0103
measure: Amount of AMG0103 excreted into urine
time frame: 1 month
arm group label: placebo
arm group type: Placebo Comparator
description: subject will receive single intradiscal injection of placebo
arm group label: AMG0103 low dose
arm group type: Experimental
description: subject will receive single intradiscal injection of AMG0103 low dose
arm group label: AMG0103 middle dose
arm group type: Experimental
description: subject will receive single intradiscal injection of AMG0103 middle dose
arm group label: AMG0103 high dose
arm group type: Experimental
description: subject will receive single intradiscal injection of AMG0103 high dose
intervention type: Drug
intervention name: Placebo
description: single intradiscal injection
arm group label: placebo
intervention type: Drug
intervention name: AMG0103
description: single intradiscal injection
arm group label: AMG0103 high dose
arm group label: AMG0103 low dose
arm group label: AMG0103 middle dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: AnGes, Inc. Clinical Development
role: Study Director
affiliation: AnGes, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Intervertebral Disc Degeneration
mesh term: Back Pain
mesh term: Low Back Pain
sharing ipd: Yes
ipd info type: Clinical Study Report (CSR)
submitted: November 30, 2022