<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/NCT03841058</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0287</org_study_id>
    <nct_id>NCT03841058</nct_id>
  </id_info>
  <brief_title>Phase II Trial of Abaloparatide vs. Placebo in Post-Menopausal Women Receiving Initial Spinal Fusion Surgery</brief_title>
  <official_title>Phase II Trial of Abaloparatide vs. Placebo in Post-Menopausal Women Receiving Initial Spinal Fusion Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital for Special Surgery, New York</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 is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot&#xD;
      to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion&#xD;
      surgery. Seventy-two women with low bone mass who are scheduled to undergo spinal fusion&#xD;
      surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide&#xD;
      subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. Outcomes&#xD;
      include surgical outcome at one year, pain, and fusion bone mass volume (FBMV) as a marker of&#xD;
      bone union at 6 months and 1 year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot&#xD;
      to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion&#xD;
      surgery. Seventy-two women with low bone mass who are scheduled to undergo spinal fusion&#xD;
      surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide&#xD;
      subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. This study&#xD;
      has 3 objectives:&#xD;
&#xD;
        1. In this pilot study we will evaluate surgical outcomes at one year and the primary&#xD;
           outcome will be fusion based on CT exam with categories of Fusion/ Indeterminate/ Not&#xD;
           fused and this will be compared between groups receiving 6 months of abaloparatide vs.&#xD;
           placebo. Secondary outcomes for surgical success will be evidence of pedicle screw&#xD;
           loosening, adjacent segment fracture and proximal junctional kyphosis. This data will be&#xD;
           used to determine effect sizes and variance to power the next larger clinical trial.&#xD;
&#xD;
        2. To determine if abaloparatide/Tymlos versus placebo leads to a faster reduction in pain&#xD;
           as assessed by both the Numeric Rating Scale (NRS) and the Oswestry Disability Index&#xD;
           (ODI) for low back pain at 6 months.&#xD;
&#xD;
        3. As an exploratory proof of concept objective we will determine if abaloparatide/Tymlos&#xD;
           versus placebo results in greater fusion bone mass volume (FBMV) as a marker of bone&#xD;
           union at 6 months and 1 year to see whether at one year post lumbar spinal fusion&#xD;
           surgery, greater FBMV is associated with improved spinal surgery outcomes including:&#xD;
           enhanced bone union, reduced pedicle screw loosening, adjacent segment fracture and&#xD;
           proximal junctional kyphosis. This would serve as evidence that FBMV can be used as an&#xD;
           early validated marker of fusion surgery success.&#xD;
&#xD;
      All analyses will be two-sided and the alpha level will be set at 0.05. FBMV, pain and&#xD;
      function will be compared by drug (Abaloparatide vs. placebo) at 6 months. Compliance will be&#xD;
      considered as taking 80% of the study drug. For the primary analysis we will evaluate bone&#xD;
      union and reduced pedicle screw loosening, adjacent segment fracture, and proximal junctional&#xD;
      kyphosis as dichotomous variables at 12 months using logistic regression and comparing the&#xD;
      placebo group to the abaloparatide group. We will also evaluate FBMV as a continuous variable&#xD;
      and evaluate differences in this outcome between abaloparatide and placebo groups at 6 months&#xD;
      as an exploratory outcome variable. We will determine if FBMV differs in those with or&#xD;
      without markers of surgical success for validity of FBMV, regardless of prior treatment&#xD;
      group. In addition, these data will be used to determine effect sizes and variance to power&#xD;
      the next larger clinical trial.&#xD;
&#xD;
      We will evaluate NRS and ODI score by using repeated measures of these variables over time by&#xD;
      treatment group and evaluate NRS at 6 months in the placebo versus abaloparatide group.&#xD;
      Comorbidity, age, prior fracture, prior use of bisphosphonates and other covariates will be&#xD;
      evaluated, via multivariable regression, as to whether they lead to a change in the estimate&#xD;
      of effect in order to be considered for inclusion in the models.&#xD;
&#xD;
      If abaloparatide can improve outcomes following lumbar spine fusion surgery, this pilot study&#xD;
      could lead to the requisite two year trial that may have an impact on the treatment of fusion&#xD;
      surgery patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 14, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Placebo will be used that will be identical to active drug in appearance</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in measure of fusion mass bridging from transverse process to transverse process</measure>
    <time_frame>one year</time_frame>
    <description>CT assessment of fusion mass using a qualitative five-point scale to assess fusion quality (1 = unfused, 2 = partial unilateral fusion, 3 = partial bilateral fusion, 4 = complete unilateral fusion, 5 = complete bilateral fusion)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in incidence of adverse surgical outcomes</measure>
    <time_frame>one year</time_frame>
    <description>Adverse outcomes include pedicle screw loosening, adjacent segment fracture and proximal junctional kyphosis will be evaluated on CT images</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain assessed by the Numeric Rating Scale</measure>
    <time_frame>6 months</time_frame>
    <description>Numeric Rating Scale (NRS) from 0 to 10 with higher scores indicating more pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain assessed by the Oswestry Disability Index</measure>
    <time_frame>6 months</time_frame>
    <description>Oswestry Disability Index for low back pain with a score of 0 to 50 points or 0 to 100%. Higher scores indicate more pain.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>CT evaluation of Fusion bone mass volume</measure>
    <time_frame>6 months and 1 year</time_frame>
    <description>fusion bone mass volume (FBMV) as a marker of bone union will be assessed on CT images</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Spinal Fusion</condition>
  <arm_group>
    <arm_group_label>Abaloparatide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Abaloparatide 80 mcg dose administered subcutaneously with a pen once daily for 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administered subcutaneously with a pen once daily for 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abaloparatide</intervention_name>
    <description>80 mcg delivered SC by a pen</description>
    <arm_group_label>Abaloparatide</arm_group_label>
    <other_name>Tymlos</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A pen to deliver a SC dose of placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>placebo pen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal women (defined as &gt;12 months since last menstrual cycle)&#xD;
&#xD;
          -  Age of 50 years or older,&#xD;
&#xD;
          -  Requiring posterolateral lumbar spine fusion surgery (L1-2; L2-3; L3-4; L4-5, L5-S1)&#xD;
             with single or multi-level fusion for degenerative conditions of the lumbar spine&#xD;
             (including lumbar degenerative disk disease, severe instability, high grade&#xD;
             spondylolisthesis, deformity, degenerative scoliosis, pseudoarthrosis, and spinal&#xD;
             stenosis) under the care of spine surgeons at the Hospital for Special Surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity to abaloparatide&#xD;
&#xD;
          2. Patients with increased risk of osteosarcoma: Paget's disease, prior radiation therapy&#xD;
&#xD;
          3. Patients with active hypercalcemia or current diagnosis of hyperparathyroidism&#xD;
&#xD;
          4. History of multiple renal calculi or renal calculus within 2 years&#xD;
&#xD;
          5. Unexplained elevations in alkaline phosphatase&#xD;
&#xD;
          6. Evidence of metastatic cancer or multiple myeloma.&#xD;
&#xD;
          7. Patients unwilling to take placebo or abaloparatide.&#xD;
&#xD;
          8. Patients whose surgery is for a revision to a prior lumbar spinal fusion surgery&#xD;
&#xD;
          9. Chronic oral steroids (&gt;= 7.5 mg prednisone/d currently and for more than 1 month) for&#xD;
             an inflammatory comorbid diagnosis&#xD;
&#xD;
         10. Patients who cannot understand and sign the informed consent&#xD;
&#xD;
         11. Patients who are unable to meet the proposed follow-up schedule&#xD;
&#xD;
         12. Patients with &gt;1 year of prior cumulative treatment with Forteo and/or Tymlos, or any&#xD;
             use of Forteo or Tymlos within the 6 months prior to enrollment.&#xD;
&#xD;
         13. Patients who have received bisphosphonate treatment of &gt;1 year in past 5 years&#xD;
&#xD;
         14. Patients who are current smokers&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emily Stein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joseph Raphael</last_name>
    <phone>(646) 797-8797</phone>
    <email>raphaelj@hss.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph Raphael</last_name>
      <phone>646-797-8797</phone>
      <email>raphaelj@hss.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 6, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>March 29, 2023</last_update_submitted>
  <last_update_submitted_qc>March 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>abalopartide</keyword>
  <keyword>pain</keyword>
  <keyword>surgical outcome</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abaloparatide</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/NCT03841058
org study id: 2018-0287
nct id: NCT03841058
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot
      to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion
      surgery. Seventy-two women with low bone mass who are scheduled to undergo spinal fusion
      surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide
      subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. Outcomes
      include surgical outcome at one year, pain, and fusion bone mass volume (FBMV) as a marker of
      bone union at 6 months and 1 year.
This is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot
      to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion
      surgery. Seventy-two women with low bone mass who are scheduled to undergo spinal fusion
      surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide
      subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. This study
      has 3 objectives:

        1. In this pilot study we will evaluate surgical outcomes at one year and the primary
           outcome will be fusion based on CT exam with categories of Fusion/ Indeterminate/ Not
           fused and this will be compared between groups receiving 6 months of abaloparatide vs.
           placebo. Secondary outcomes for surgical success will be evidence of pedicle screw
           loosening, adjacent segment fracture and proximal junctional kyphosis. This data will be
           used to determine effect sizes and variance to power the next larger clinical trial.

        2. To determine if abaloparatide/Tymlos versus placebo leads to a faster reduction in pain
           as assessed by both the Numeric Rating Scale (NRS) and the Oswestry Disability Index
           (ODI) for low back pain at 6 months.

        3. As an exploratory proof of concept objective we will determine if abaloparatide/Tymlos
           versus placebo results in greater fusion bone mass volume (FBMV) as a marker of bone
           union at 6 months and 1 year to see whether at one year post lumbar spinal fusion
           surgery, greater FBMV is associated with improved spinal surgery outcomes including:
           enhanced bone union, reduced pedicle screw loosening, adjacent segment fracture and
           proximal junctional kyphosis. This would serve as evidence that FBMV can be used as an
           early validated marker of fusion surgery success.

      All analyses will be two-sided and the alpha level will be set at 0.05. FBMV, pain and
      function will be compared by drug (Abaloparatide vs. placebo) at 6 months. Compliance will be
      considered as taking 80% of the study drug. For the primary analysis we will evaluate bone
      union and reduced pedicle screw loosening, adjacent segment fracture, and proximal junctional
      kyphosis as dichotomous variables at 12 months using logistic regression and comparing the
      placebo group to the abaloparatide group. We will also evaluate FBMV as a continuous variable
      and evaluate differences in this outcome between abaloparatide and placebo groups at 6 months
      as an exploratory outcome variable. We will determine if FBMV differs in those with or
      without markers of surgical success for validity of FBMV, regardless of prior treatment
      group. In addition, these data will be used to determine effect sizes and variance to power
      the next larger clinical trial.

      We will evaluate NRS and ODI score by using repeated measures of these variables over time by
      treatment group and evaluate NRS at 6 months in the placebo versus abaloparatide group.
      Comorbidity, age, prior fracture, prior use of bisphosphonates and other covariates will be
      evaluated, via multivariable regression, as to whether they lead to a change in the estimate
      of effect in order to be considered for inclusion in the models.

      If abaloparatide can improve outcomes following lumbar spine fusion surgery, this pilot study
      could lead to the requisite two year trial that may have an impact on the treatment of fusion
      surgery patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Placebo will be used that will be identical to active drug in appearance
measure: Difference in measure of fusion mass bridging from transverse process to transverse process
time frame: one year
description: CT assessment of fusion mass using a qualitative five-point scale to assess fusion quality (1 = unfused, 2 = partial unilateral fusion, 3 = partial bilateral fusion, 4 = complete unilateral fusion, 5 = complete bilateral fusion)
measure: Difference in incidence of adverse surgical outcomes
time frame: one year
description: Adverse outcomes include pedicle screw loosening, adjacent segment fracture and proximal junctional kyphosis will be evaluated on CT images
measure: Pain assessed by the Numeric Rating Scale
time frame: 6 months
description: Numeric Rating Scale (NRS) from 0 to 10 with higher scores indicating more pain.
measure: Pain assessed by the Oswestry Disability Index
time frame: 6 months
description: Oswestry Disability Index for low back pain with a score of 0 to 50 points or 0 to 100%. Higher scores indicate more pain.
measure: CT evaluation of Fusion bone mass volume
time frame: 6 months and 1 year
description: fusion bone mass volume (FBMV) as a marker of bone union will be assessed on CT images
arm group label: Abaloparatide
arm group type: Active Comparator
description: Abaloparatide 80 mcg dose administered subcutaneously with a pen once daily for 6 months
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo administered subcutaneously with a pen once daily for 6 months
intervention type: Drug
intervention name: Abaloparatide
description: 80 mcg delivered SC by a pen
arm group label: Abaloparatide
other name: Tymlos
intervention type: Drug
intervention name: Placebo
description: A pen to deliver a SC dose of placebo
arm group label: Placebo
other name: placebo pen
criteria: 
gender: Female
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Emily Stein, MD
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
last name: Joseph Raphael
phone: (646) 797-8797
email: raphaelj@hss.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Abaloparatide
sharing ipd: No