<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/NCT03246399</url>
  </required_header>
  <id_info>
    <org_study_id>SM04690-DDD-01</org_study_id>
    <nct_id>NCT03246399</nct_id>
  </id_info>
  <brief_title>A Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease</brief_title>
  <official_title>A Phase 1, Open-label Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biosplice Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biosplice 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      SM04690-DDD-01 is a Phase 1, open-label, dose escalation study. SM04690 Injectable Suspension&#xD;
      will be administered via a single intradiscal injection to subjects with degenerative disc&#xD;
      disease (DDD) under fluoroscopic guidance. Groups of 6 subjects will be enrolled in&#xD;
      successive cohorts. Subjects will participate in a 6 month follow-up period. Clinic visits&#xD;
      will be Screening, Treatment Visit Day 1, and Follow-up Visit Days 2, 15, 28, 60, 90, 135,&#xD;
      and 180.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study stopped due to business reasons, following full enrollment of the first dose cohort.&#xD;
  </why_stopped>
  <start_date type="Actual">July 26, 2017</start_date>
  <completion_date type="Actual">December 4, 2018</completion_date>
  <primary_completion_date type="Actual">November 14, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability: treatment emergent adverse events (TEAEs)</measure>
    <time_frame>Day 180</time_frame>
    <description>Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by TEAEs during the entire treatment and observation period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability: change from baseline in electrocardiogram (ECG) parameters</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in ECG parameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability: change from baseline in physical examination</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in physical examination (number of subjects with clinically significant change in physical examination)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability: change from baseline in clinical laboratory tests</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in clinical laboratory tests (number of subjects with clinically significant changes in laboratory test parameters)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability: change from baseline in vital signs</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in vital signs (number of subjects with clinically significant changes in vital signs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of dose-limiting toxicities (DLTs)</measure>
    <time_frame>Day 180</time_frame>
    <description>Evaluate incidence and severity of DLTs in each cohort</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics (PK) of SM04690: Cmax</measure>
    <time_frame>Day 1</time_frame>
    <description>Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK of SM04690: tmax</measure>
    <time_frame>Day 1</time_frame>
    <description>Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK of SM04690: AUC</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK of SM04690: half-life</measure>
    <time_frame>Day 1</time_frame>
    <description>Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in spine bone mineral density</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline spine bone mineral density as measured by dual-energy x-ray absorptiometry (DXA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hip bone mineral density</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline hip bone mineral density as measured by DXA</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in lumbar back pain</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline lumbar back pain using the Visual Analog Scale (VAS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in disability</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline disability as measured by Oswestry disability index (ODI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in disease activity by physician assessment</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline disease activity using Physician Global Assessment (PGA)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in treated intervertebral discs</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline in treated intervertebral discs by modified Pfirrmann grade using Magnetic Resonance Imaging (MRI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in disc space height</measure>
    <time_frame>Baseline and Day 180</time_frame>
    <description>Evaluate change from baseline in disc space height by radiograph</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Degenerative Disc Disease</condition>
  <arm_group>
    <arm_group_label>0.03mg SM04690</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.03mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.07mg SM04690</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.07mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.15mg SM04690</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.15mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SM04690</intervention_name>
    <description>suspension formulation of SM04690, delivered via intradiscal injection (single injection)</description>
    <arm_group_label>0.03mg SM04690</arm_group_label>
    <arm_group_label>0.07mg SM04690</arm_group_label>
    <arm_group_label>0.15mg SM04690</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Degenerative disease in a maximum of two and a minimum of one lumbar disc (L4/L5 or&#xD;
             L5/S1)&#xD;
&#xD;
          -  Persistent low back pain due to DDD for at least 3 months prior to study start&#xD;
&#xD;
          -  Full understanding of the requirements of the study and willingness to comply with all&#xD;
             study visits and assessments&#xD;
&#xD;
          -  Subjects must have read and understood the informed consent form, and must have signed&#xD;
             it prior to any study-related procedure being performed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant, lactating, or have a positive pregnancy result at study start&#xD;
&#xD;
          -  Women of child bearing potential who are sexually active and are not willing to use a&#xD;
             highly effective method of birth control during the study period&#xD;
&#xD;
          -  Males who are sexually active and have a partner who is capable of becoming pregnant,&#xD;
             neither of whom have had surgery to become sterilized or whom are not using a highly&#xD;
             effective method of birth control&#xD;
&#xD;
          -  Body mass index (BMI) &gt; 35&#xD;
&#xD;
          -  Previous participation in a Samumed clinical trial investigating SM04690&#xD;
&#xD;
          -  History of compression fractures and/or osteoporosis&#xD;
&#xD;
          -  Any herniation in the lumbar spine as identified by MRI&#xD;
&#xD;
          -  Congenital or acquired diseases leading to spine deformations&#xD;
&#xD;
          -  History of hypersensitivity or allergies to any ingredient of the study medication&#xD;
&#xD;
          -  Participation in a clinical research trial that included the receipt of an&#xD;
             investigational product or any experimental therapeutic procedure, or an observational&#xD;
             research trial related to DDD within 8 weeks prior to any study injection, or planned&#xD;
             participation in any such trial; the last date of participation in the trial, not the&#xD;
             last date of receipt of investigational product, must be at least 8 weeks prior to&#xD;
             study start&#xD;
&#xD;
          -  Poor peripheral venous access&#xD;
&#xD;
          -  Any contraindications to MRI according to MRI guidelines&#xD;
&#xD;
          -  History of malignancy; however, subjects with prior history of in situ cancer or basal&#xD;
             or squamous cell skin cancer, completely cured, are eligible.&#xD;
&#xD;
          -  Any diagnosed psychiatric condition that includes, but is not limited to, a history of&#xD;
             mania, bipolar disorder, psychotic disorder, schizophrenia, schizoaffective disorder,&#xD;
             major depressive disorder, or generalized anxiety disorder&#xD;
&#xD;
          -  Prior surgical procedures (e.g., discectomy, intradiscal electrothermal therapy,&#xD;
             intradiscal radiofrequency, artificial disc replacement, and interbody fusion) on the&#xD;
             lumbar spine&#xD;
&#xD;
          -  Any planned or elective surgery during the study period&#xD;
&#xD;
          -  Any known active infections, including hepatitis B or hepatitis C infection, and/or&#xD;
             infections that may compromise the immune system such as human immunodeficiency virus&#xD;
             (HIV)&#xD;
&#xD;
          -  Current or prior history of any spinal infection (i.e., discitis, septic arthritis, or&#xD;
             epidural abscess)&#xD;
&#xD;
          -  Any lumbar intradiscal injection procedure (e.g., injection of corticosteroids,&#xD;
             methylene blue, dextrose, etc.), myelograms, discography, and/or lumbar epidural or&#xD;
             transforaminal injections with corticosteroids or nerve-blocking anesthetics (e.g,&#xD;
             lidocaine, bupivacaine) within 3 months prior to study start&#xD;
&#xD;
          -  Any electrotherapy (i.e., transcutaneous electrical nerve stimulation [TENS] unit) or&#xD;
             acupuncture for DDD within 4 weeks prior to study medication injection&#xD;
&#xD;
          -  History of or current/pending disability claim, workers' compensation, or&#xD;
             litigation(s) related to back pain/injury&#xD;
&#xD;
          -  Subjects who are immediate family members (spouse, parent, child, or sibling;&#xD;
             biological or legally adopted) of personnel directly affiliated with the study at any&#xD;
             investigative site, or are directly affiliated with the study at any investigative&#xD;
             site&#xD;
&#xD;
          -  Subjects employed by Samumed, LLC, or any of its affiliates or development partners&#xD;
             (that is, an employee, temporary contract worker, or designee) responsible for the&#xD;
             conduct of the study, or who are immediate family members (spouse, parent, child, or&#xD;
             sibling; biological or legally adopted) of said employees responsible for the conduct&#xD;
             of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yusuf Yazici, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Biosplice Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>June 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>April 19, 2019</last_update_submitted>
  <last_update_submitted_qc>April 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SM04690</keyword>
  <keyword>Wnt pathway</keyword>
  <keyword>Samumed</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Diseases</mesh_term>
    <mesh_term>Intervertebral Disc Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lorecivivint</mesh_term>
  </intervention_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/NCT03246399
org study id: SM04690-DDD-01
nct id: NCT03246399
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
SM04690-DDD-01 is a Phase 1, open-label, dose escalation study. SM04690 Injectable Suspension
      will be administered via a single intradiscal injection to subjects with degenerative disc
      disease (DDD) under fluoroscopic guidance. Groups of 6 subjects will be enrolled in
      successive cohorts. Subjects will participate in a 6 month follow-up period. Clinic visits
      will be Screening, Treatment Visit Day 1, and Follow-up Visit Days 2, 15, 28, 60, 90, 135,
      and 180.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability: treatment emergent adverse events (TEAEs)
time frame: Day 180
description: Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by TEAEs during the entire treatment and observation period
measure: Safety and tolerability: change from baseline in electrocardiogram (ECG) parameters
time frame: Baseline and Day 180
description: Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in ECG parameters
measure: Safety and tolerability: change from baseline in physical examination
time frame: Baseline and Day 180
description: Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in physical examination (number of subjects with clinically significant change in physical examination)
measure: Safety and tolerability: change from baseline in clinical laboratory tests
time frame: Baseline and Day 180
description: Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in clinical laboratory tests (number of subjects with clinically significant changes in laboratory test parameters)
measure: Safety and tolerability: change from baseline in vital signs
time frame: Baseline and Day 180
description: Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in vital signs (number of subjects with clinically significant changes in vital signs)
measure: Incidence of dose-limiting toxicities (DLTs)
time frame: Day 180
description: Evaluate incidence and severity of DLTs in each cohort
measure: Pharmacokinetics (PK) of SM04690: Cmax
time frame: Day 1
description: Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension
measure: PK of SM04690: tmax
time frame: Day 1
description: Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension
measure: PK of SM04690: AUC
time frame: Day 1
description: Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension
measure: PK of SM04690: half-life
time frame: Day 1
description: Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension
measure: Change in spine bone mineral density
time frame: Baseline and Day 180
description: Evaluate change from baseline spine bone mineral density as measured by dual-energy x-ray absorptiometry (DXA)
measure: Change in hip bone mineral density
time frame: Baseline and Day 180
description: Evaluate change from baseline hip bone mineral density as measured by DXA
measure: Change in lumbar back pain
time frame: Baseline and Day 180
description: Evaluate change from baseline lumbar back pain using the Visual Analog Scale (VAS)
measure: Change in disability
time frame: Baseline and Day 180
description: Evaluate change from baseline disability as measured by Oswestry disability index (ODI)
measure: Change in disease activity by physician assessment
time frame: Baseline and Day 180
description: Evaluate change from baseline disease activity using Physician Global Assessment (PGA)
measure: Change in treated intervertebral discs
time frame: Baseline and Day 180
description: Evaluate change from baseline in treated intervertebral discs by modified Pfirrmann grade using Magnetic Resonance Imaging (MRI)
measure: Change in disc space height
time frame: Baseline and Day 180
description: Evaluate change from baseline in disc space height by radiograph
arm group label: 0.03mg SM04690
arm group type: Experimental
description: 0.03mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
arm group label: 0.07mg SM04690
arm group type: Experimental
description: 0.07mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
arm group label: 0.15mg SM04690
arm group type: Experimental
description: 0.15mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
intervention type: Drug
intervention name: SM04690
description: suspension formulation of SM04690, delivered via intradiscal injection (single injection)
arm group label: 0.03mg SM04690
arm group label: 0.07mg SM04690
arm group label: 0.15mg SM04690
criteria: 
gender: All
minimum age: 25 Years
maximum age: 55 Years
healthy volunteers: No
last name: Yusuf Yazici, M.D.
role: Study Director
affiliation: Biosplice Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Spinal Diseases
mesh term: Intervertebral Disc Degeneration
mesh term: Lorecivivint
sharing ipd: No