xml: <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/NCT05961956</url>
    </required_header>
    <id_info>
      <org_study_id>NVDX3-CLN02</org_study_id>
      <secondary_id>2022-002771-11</secondary_id>
      <nct_id>NCT05961956</nct_id>
    </id_info>
    <brief_title>Study With NVDX3 for Treatment of Low Grade Degenerative Lumbar Spondylolisthesis</brief_title>
    <official_title>A Proof-of-concept Study With NVDX3, an Osteogenic Implant of Human Allogenic Origin, in the Treatment of Low Grade Degenerative Lumbar Spondylolisthesis by Interbody Spine Fusion in Adults.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Novadip Biosciences</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>PrimeVigilance</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Data Investigation Company Europe (DICE)</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Novadip Biosciences</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>
        Prospective, single arm, single-center clinical study to test NVDX3 in patients suffering&#xD;
        from low grade one level degenerative lumbar (L1 - S1) spondylolisthesis. NVDX3 will be&#xD;
        implanted during a single surgical intervention.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a prospective, single arm, single-center PoC study in adult patients, suffering from&#xD;
        a degenerative lumbar (L1-S1) spondylolisthesis, treated by spondylodesis in which NVDX3, an&#xD;
        osteogenic implant from human allogeneic origin is used. The screening and implant surgery&#xD;
        visits will be used as the reference timepoint respectively for the clinical and the&#xD;
        radiological efficacy outcome evaluations.&#xD;
  &#xD;
        As per standard of care, patients with DLS are followed up to 12 months post-intervention. In&#xD;
        the context of this trial, patient safety and IMP efficacy will be followed up to 24 months&#xD;
        post-implant surgery.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">November 15, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Primary Safety Endpoint</measure>
      <time_frame>Up to 24 months post implant surgery</time_frame>
      <description>Description of all SAEs and NVDX3 related AEs</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Safety: all acute SAEs and NVDX3 related AEs</measure>
      <time_frame>Between screening (V1) and 6 weeks post-IS (V4)</time_frame>
      <description>Description of all acute SAEs and NVDX3 related AEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: all SAEs and NVDX3 related AEs</measure>
      <time_frame>Beyond 6 weeks (V4 excluded) until 12 months post-IS</time_frame>
      <description>Description of all SAEs and NVDX3 related AEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: all SAEs and NVDX3 related AEs</measure>
      <time_frame>Beyond 12 months (V7 excluded) until 24 months post-IS</time_frame>
      <description>Description of all SAEs and NVDX3 related AEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: TEAEs</measure>
      <time_frame>a. Between screening and week 6 (V4 included) b. Between week 6 (V4 excluded) till month 12 (V7 included) c. Between month 12 (V7 excluded) till month 24 (V9 included) d. Full study duration</time_frame>
      <description>Description of Treatment Emergent AEs (TEAEs)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: related and unexpected (S)AEs</measure>
      <time_frame>Between screening (v1) till 24 months post-IS</time_frame>
      <description>Description of related and unexpected (S)AEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: AESI</measure>
      <time_frame>Between screening (v1) till 24 months post-IS</time_frame>
      <description>Description of AE of Special Interest (AESI)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: Lab data</measure>
      <time_frame>Between screening (v1) till 24 months post-IS</time_frame>
      <description>Description of lab data</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety: vital signs: physiological parameters</measure>
      <time_frame>Between screening (v1) till 24 months post-IS</time_frame>
      <description>Description of vital signs: body temperature, pulse rate, respiratory rate and blood pressure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Radiological assessments</measure>
      <time_frame>a. 4 and 12 months post-IS based on CT compared to Hospital Discharge image acquisition and b. 24-months post-IS based on X-rays compared to the first post-operative X-ray acquisitions taken at 6 weeks post-IS</time_frame>
      <description>Evaluate presence of cortical and trabecular bone formation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Radiological assessments</measure>
      <time_frame>a. 4 and 12 months post-IS based on CT compared to Hospital Discharge image acquisition and b. 24-months post-IS based on X-rays compared to the first post-operative X-ray acquisitions taken at 6 weeks post-IS</time_frame>
      <description>Evaluate presence of spinal fusion (Interbody/disc and facet joint fusion status)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Radiological assessments</measure>
      <time_frame>At Hospital Discharge, 4 and 12 months post-IS</time_frame>
      <description>Measure the average disc height variations based on CT</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Clinical assessments: investigator questionnaire</measure>
      <time_frame>At hospital discharge, 6 weeks, 4-, 6-, 12-, 18- and 24-months post-IS</time_frame>
      <description>Physician rated Clinical Global Impression scale (CGI)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Clinical assessments: patient questionnaire</measure>
      <time_frame>At hospital discharge, 6 weeks, 4-, 6-, 12-, 18- and 24-months post-IS</time_frame>
      <description>Patient reported Functional assessments using the ODI</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy: Clinical assessments: patient questionnaire</measure>
      <time_frame>At hospital discharge, 6 weeks, 4-, 6-, 12-, 18- and 24-months post-IS</time_frame>
      <description>Patient reported Numeric rating scale (NRS) for pain</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">10</enrollment>
    <condition>Degenerative Lumbar Spondylolisthesis</condition>
    <arm_group>
      <arm_group_label>NVDX3 osteogenic implant</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>NVDX3</intervention_name>
      <description>NVDX3 is implanted during a single surgical intervention.</description>
      <arm_group_label>NVDX3 osteogenic implant</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female patients aged ≥18 years to ≤80 years.&#xD;
  &#xD;
            2. Patient diagnosed with symptomatic DLS with confirmed:&#xD;
  &#xD;
                 1. Classification: Meyerding grade I or II DLS&#xD;
  &#xD;
                 2. One vertebral segment within the lumbar region from L1-S1&#xD;
  &#xD;
                 3. Availability of AP and LAT X-ray, MRI and/or CT scan at which the diagnosis was&#xD;
                    made.&#xD;
  &#xD;
            3. The estimated volume of targeted disc space to be filled (both inside and around the&#xD;
               interbody cage) should not exceed 10cc.&#xD;
  &#xD;
            4. Clinically meaningful pain or neurological symptoms with or without claudication&#xD;
               confirmed by a preoperative ODI score &gt;30, which have been unresponsive to a minimum&#xD;
               of 3 consecutive months of structured conservative medical management (including at&#xD;
               least pain medication, activity modification, and daily exercise).&#xD;
  &#xD;
            5. Patient is eligible for surgery by minimally invasive or open transforaminal lumbar&#xD;
               interbody fusion (TLIF)3.&#xD;
  &#xD;
            6. Patient has understood and accepted to participate in the study according to all study&#xD;
               procedures by signing the informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of previously attempted spinal fusion at the same vertebral level, or at a&#xD;
               level immediately adjacent to the level intended to undergo the spondylodesis.&#xD;
               Decompressive surgery alone (laminectomy) is not an exclusion criterion.&#xD;
  &#xD;
            2. Patient with a BMI of ≥35.&#xD;
  &#xD;
            3. Presence of clinically significant infection at the target implant site or presence of&#xD;
               any systemic infection.&#xD;
  &#xD;
            4. History of allergic reaction or any anticipated hypersensitivity to any of the&#xD;
               following:&#xD;
  &#xD;
                 1. Osteosynthesis materials (eg.cage, screws, rods,…),&#xD;
  &#xD;
                 2. Anesthetic agents,&#xD;
  &#xD;
                 3. Components of the NVDX3 implant&#xD;
  &#xD;
            5. Presence of any auto-immune disease, with exception of well controlled diabetes type-1&#xD;
               or II, or auto-immune thyroid disorders.&#xD;
  &#xD;
            6. Positive serology for human immunodeficiency virus (HIV), HBcAb and/or HBsAg.&#xD;
  &#xD;
            7. Presence of an active tumor.&#xD;
  &#xD;
            8. Documented metabolic bone disease or any disorder, such as but not limited to&#xD;
               high-risk osteoporosis, that could interfere with the bone healing and bone&#xD;
               metabolism.&#xD;
  &#xD;
            9. Documented disease limiting mobility and functional assessments.&#xD;
  &#xD;
           10. Chronic, ongoing, or planned use of medications that might affect bone metabolism or&#xD;
               bone quality such as bisphosphonates, steroids, methotrexate, anticoagulants,&#xD;
               immunosuppressants or immunotherapy.&#xD;
  &#xD;
           11. Excessive smoking or history of chronic alcohol or drug abuse within the 12 months&#xD;
               prior to screening&#xD;
  &#xD;
           12. Use of any investigational drug within 60 days prior to screening.&#xD;
  &#xD;
           13. Pregnant women or women of childbearing potential (WOCBP) not agreeing to use&#xD;
               effective an effective method of birth control4 during the course of the study. Note:&#xD;
               WOCBP including peri-menopausal women who have had a menstrual period within 1 year&#xD;
               prior to surgery have to have a negative pregnancy test before entering in the study.&#xD;
  &#xD;
           14. Any other psychosocial, mental and physical condition which, in the opinion of the&#xD;
               investigator, could interfere with the trial conduct, the patient's compliance or&#xD;
               influence interpretation of the results.&#xD;
  &#xD;
           15. Patient with historically elevated radiation exposure levels that could in the opinion&#xD;
               of the investigator introduce unacceptable radiation risks for the patient, when being&#xD;
               accumulated with the radiological examinations planned in this study.&#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>Anas Ibrahim Ali Dyab, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Centre Hospitalier du Luxembourg</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Denis Dufrane, MD</last_name>
      <phone>003210779220</phone>
      <email>clinical@novadip.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Dieter Frijns, MSc</last_name>
      <phone>003210779220</phone>
      <email>clinical@novadip.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Centre Hospitalier de Luxembourg</name>
        <address>
          <city>Luxembourg</city>
          <zip>1210</zip>
          <country>Luxembourg</country>
        </address>
      </facility>
      <contact>
        <last_name>Anas Ibrahim Ali Dyab, MD</last_name>
        <email>dyabanas@hotmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Luxembourg</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>July 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Spondylolisthesis</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05961956
  org study id: NVDX3-CLN02
  secondary id: 2022-002771-11
  nct id: NCT05961956
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Prospective, single arm, single-center clinical study to test NVDX3 in patients suffering
        from low grade one level degenerative lumbar (L1 - S1) spondylolisthesis. NVDX3 will be
        implanted during a single surgical intervention.
  This is a prospective, single arm, single-center PoC study in adult patients, suffering from
        a degenerative lumbar (L1-S1) spondylolisthesis, treated by spondylodesis in which NVDX3, an
        osteogenic implant from human allogeneic origin is used. The screening and implant surgery
        visits will be used as the reference timepoint respectively for the clinical and the
        radiological efficacy outcome evaluations.
  
        As per standard of care, patients with DLS are followed up to 12 months post-intervention. In
        the context of this trial, patient safety and IMP efficacy will be followed up to 24 months
        post-implant surgery.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Primary Safety Endpoint
  time frame: Up to 24 months post implant surgery
  description: Description of all SAEs and NVDX3 related AEs
  measure: Safety: all acute SAEs and NVDX3 related AEs
  time frame: Between screening (V1) and 6 weeks post-IS (V4)
  description: Description of all acute SAEs and NVDX3 related AEs
  measure: Safety: all SAEs and NVDX3 related AEs
  time frame: Beyond 6 weeks (V4 excluded) until 12 months post-IS
  description: Description of all SAEs and NVDX3 related AEs
  measure: Safety: all SAEs and NVDX3 related AEs
  time frame: Beyond 12 months (V7 excluded) until 24 months post-IS
  description: Description of all SAEs and NVDX3 related AEs
  measure: Safety: TEAEs
  time frame: a. Between screening and week 6 (V4 included) b. Between week 6 (V4 excluded) till month 12 (V7 included) c. Between month 12 (V7 excluded) till month 24 (V9 included) d. Full study duration
  description: Description of Treatment Emergent AEs (TEAEs)
  measure: Safety: related and unexpected (S)AEs
  time frame: Between screening (v1) till 24 months post-IS
  description: Description of related and unexpected (S)AEs
  measure: Safety: AESI
  time frame: Between screening (v1) till 24 months post-IS
  description: Description of AE of Special Interest (AESI)
  measure: Safety: Lab data
  time frame: Between screening (v1) till 24 months post-IS
  description: Description of lab data
  measure: Safety: vital signs: physiological parameters
  time frame: Between screening (v1) till 24 months post-IS
  description: Description of vital signs: body temperature, pulse rate, respiratory rate and blood pressure
  measure: Efficacy: Radiological assessments
  time frame: a. 4 and 12 months post-IS based on CT compared to Hospital Discharge image acquisition and b. 24-months post-IS based on X-rays compared to the first post-operative X-ray acquisitions taken at 6 weeks post-IS
  description: Evaluate presence of cortical and trabecular bone formation
  measure: Efficacy: Radiological assessments
  time frame: a. 4 and 12 months post-IS based on CT compared to Hospital Discharge image acquisition and b. 24-months post-IS based on X-rays compared to the first post-operative X-ray acquisitions taken at 6 weeks post-IS
  description: Evaluate presence of spinal fusion (Interbody/disc and facet joint fusion status)
  measure: Efficacy: Radiological assessments
  time frame: At Hospital Discharge, 4 and 12 months post-IS
  description: Measure the average disc height variations based on CT
  measure: Efficacy: Clinical assessments: investigator questionnaire
  time frame: At hospital discharge, 6 weeks, 4-, 6-, 12-, 18- and 24-months post-IS
  description: Physician rated Clinical Global Impression scale (CGI)
  measure: Efficacy: Clinical assessments: patient questionnaire
  time frame: At hospital discharge, 6 weeks, 4-, 6-, 12-, 18- and 24-months post-IS
  description: Patient reported Functional assessments using the ODI
  measure: Efficacy: Clinical assessments: patient questionnaire
  time frame: At hospital discharge, 6 weeks, 4-, 6-, 12-, 18- and 24-months post-IS
  description: Patient reported Numeric rating scale (NRS) for pain
  arm group label: NVDX3 osteogenic implant
  arm group type: Experimental
  intervention type: Drug
  intervention name: NVDX3
  description: NVDX3 is implanted during a single surgical intervention.
  arm group label: NVDX3 osteogenic implant
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Anas Ibrahim Ali Dyab, MD
  role: Principal Investigator
  affiliation: Centre Hospitalier du Luxembourg
  last name: Denis Dufrane, MD
  phone: 003210779220
  email: clinical@novadip.com
  last name: Dieter Frijns, MSc
  phone: 003210779220
  email: clinical@novadip.com
  facility: 
  contact: 
  country: Luxembourg
  responsible party type: Sponsor
  mesh term: Spondylolisthesis