<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/NCT02230917</url>
  </required_header>
  <id_info>
    <org_study_id>IUCRO-0428</org_study_id>
    <nct_id>NCT02230917</nct_id>
  </id_info>
  <brief_title>A Phase IIa Study of Sotatercept on Bone Mass and Turnover in Patients With Multiple Myeloma</brief_title>
  <official_title>A Phase IIa Study of Sotatercept on Bone Mass and Turnover in Patients With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rebecca Silbermann</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Indiana University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lytic bone disease continues to be one of the most devastating complications of multiple&#xD;
      myeloma (MM) despite recent and dramatic advancements in MM management, and bone lesions&#xD;
      persist and can continue to significantly impact a patient's morbidity, even when an&#xD;
      individual's myeloma is otherwise under good control. To date, no agent has been shown to&#xD;
      have a prolonged bone anabolic response in myeloma.&#xD;
&#xD;
      Preliminary studies treating healthy postmenopausal women with a single dose of sotatercept&#xD;
      demonstrated a rapid and sustained increase in serum biochemical markers of bone formation&#xD;
      and a decrease in markers of bone resorption. Similarly, the murine analog to sotatercept,&#xD;
      RAP-011, increases bone mineral density and strength in murine studies of both normal animals&#xD;
      and models of bone loss. We hypothesize that sotatercept will provide an anabolic response&#xD;
      for bone in myeloma patients with bone disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</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>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of biochemical bone turnover</measure>
    <time_frame>Average of 3 months</time_frame>
    <description>The presence of change in biochemical markers of bone turnover during treatment with sotatercept will be examined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events related to sotatercept</measure>
    <time_frame>Average of 21 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone marrow density</measure>
    <time_frame>Average of 12 months</time_frame>
    <description>Change in bone mineral density of the femoral neck, forearm and spine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in biochemical myeloma markers</measure>
    <time_frame>Average of 3 months</time_frame>
    <description>The change in myeloma markers will be determined by quantifying immunoglobulins, SPEP, UPEP and free light chains.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Size of target bone lesions</measure>
    <time_frame>Average of 6 months</time_frame>
    <description>Measure the change in size of target bone lesions using x-ray of target skeletal lesions.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Sotatercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sotatercept 0.2 mg/kg will be administered every 21 days for 12 doses subcutaneously into the upper arm, abdomen or thigh.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.2 mg/kg of normal saline will be administered subcutaneously in the upper arm, abdomen or thigh for 21 days for 12 doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sotatercept</intervention_name>
    <arm_group_label>Sotatercept</arm_group_label>
    <other_name>ACE-011</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 18 years at the time of signing the informed consent form.&#xD;
&#xD;
          2. Documented diagnosis of Multiple Myeloma, currently with complete response (CR) or&#xD;
             very good partial response (VGPR) (as defined by IMWG criteria), at least two years&#xD;
             after induction therapy or autologous stem cell transplant.&#xD;
&#xD;
          3. Patients must not be receiving anti-Myeloma therapy (including maintenance therapy).&#xD;
&#xD;
          4. Disease response must be confirmed with repeat laboratory studies at least 30 days&#xD;
             apart.&#xD;
&#xD;
          5. Radiologic evidence of at least 1 measurable lytic lesion in the arm, pelvis or leg.&#xD;
             Completion of two years monthly zoledronic acid therapy.&#xD;
&#xD;
          6. Eastern Cooperative Group (ECOG) performance status 0- 2&#xD;
&#xD;
          7. Creatinine ≤1.5 x upper limit of normal (ULN) or ≥40 mL/min&#xD;
&#xD;
          8. Total bilirubin ≤ 3.0 mg/dL (bilirubin ≤1.5 x upper limit normal)&#xD;
&#xD;
          9. AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN and ≤ 5.0 ULN for subjects with liver metastases&#xD;
&#xD;
         10. Hemoglobin ≥ 7.5 g/dL and ≤ 13 g/dL&#xD;
&#xD;
         11. Absolute neutrophil count ≥1500/uL&#xD;
&#xD;
         12. Platelet count ≥ 75,000/ uL (&gt;72 hours since prior platelet transfusion)&#xD;
&#xD;
         13. Corrected calcium within normal limits, previous hypercalcemia allowed&#xD;
&#xD;
         14. Females of childbearing potential must use a highly effective method of birth control&#xD;
             for at least 28 days before starting study, during participation and at least 112 days&#xD;
             following last dose of sotatercept.&#xD;
&#xD;
         15. Males must use latex condom or non-latex condom not made of (animal) membrane during&#xD;
             any sexual contact with female of childbearing potential while participating in the&#xD;
             study and for at least 112 days following the last dose of sotatercept, even if he has&#xD;
             undergone successful vasectomy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of thrombosis, deep vein thrombosis, pulmonary emboli, or embolic stroke AND&#xD;
             have not been stable on anticoagulants within the past 6 months. Local central line&#xD;
             thrombosis is allowed.&#xD;
&#xD;
          2. History of polycythemia&#xD;
&#xD;
          3. Uncontrolled hypertension (systolic blood pressure &gt; 140 mmHg or diastolic blood&#xD;
             pressure &gt; 90 mmHg.)&#xD;
&#xD;
          4. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant&#xD;
             proteins or excipients in investigational product.&#xD;
&#xD;
          5. Current use of anti-cancer cytotoxic chemotherapeutic agents.&#xD;
&#xD;
          6. Major surgery within 30 days of Day 1 of trial.&#xD;
&#xD;
          7. Incomplete recovery or incomplete healing of wounds from previous surgery, as&#xD;
             determined by treating Investigator.&#xD;
&#xD;
          8. Subjects with classification of 3 or higher heart failure as classified by the New&#xD;
             York Heart Association (NYHA). Please see Appendix IV.&#xD;
&#xD;
          9. Women who are pregnant or breastfeeding or planning to become pregnant or breastfeed&#xD;
             during the period of treatment and for 112 days following the last dose of&#xD;
             sotatercept.&#xD;
&#xD;
         10. Treatment with another investigational drug or device within 28 days prior to Day 1,&#xD;
             or if the half-life of the previous product is known, within 5 times the half-life of&#xD;
             the investigational drug prior to dosing, whichever is longer.&#xD;
&#xD;
         11. Prior exposure to sotatercept.&#xD;
&#xD;
         12. Any significant medical condition, laboratory abnormality, or psychiatric illness&#xD;
             that, as determined by the treating Investigator, would prevent the subject from&#xD;
             participating in the study or providing written informed consent.&#xD;
&#xD;
         13. Any condition including the presence of laboratory abnormality that, as determined by&#xD;
             the treating Investigator, places the subject at unacceptable risk if he/she were to&#xD;
             participate in the study.&#xD;
&#xD;
         14. Known positive for human immunodeficiency virus (HIV)&#xD;
&#xD;
         15. Known positive for infectious hepatitis type C or active infectious hepatitis type B.&#xD;
&#xD;
         16. Any condition that, as determined by the treating Investigator, confounds the&#xD;
             interpretation of data from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebecca Silbermann, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Indiana University Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>August 30, 2016</last_update_submitted>
  <last_update_submitted_qc>August 30, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 1, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>Rebecca Silbermann</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <!-- 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/NCT02230917
org study id: IUCRO-0428
nct id: NCT02230917
lead sponsor: 
collaborator: 
has dmc: Yes
Lytic bone disease continues to be one of the most devastating complications of multiple
      myeloma (MM) despite recent and dramatic advancements in MM management, and bone lesions
      persist and can continue to significantly impact a patient's morbidity, even when an
      individual's myeloma is otherwise under good control. To date, no agent has been shown to
      have a prolonged bone anabolic response in myeloma.

      Preliminary studies treating healthy postmenopausal women with a single dose of sotatercept
      demonstrated a rapid and sustained increase in serum biochemical markers of bone formation
      and a decrease in markers of bone resorption. Similarly, the murine analog to sotatercept,
      RAP-011, increases bone mineral density and strength in murine studies of both normal animals
      and models of bone loss. We hypothesize that sotatercept will provide an anabolic response
      for bone in myeloma patients with bone disease.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
measure: Presence of biochemical bone turnover
time frame: Average of 3 months
description: The presence of change in biochemical markers of bone turnover during treatment with sotatercept will be examined.
measure: Number of Adverse Events related to sotatercept
time frame: Average of 21 days
measure: Bone marrow density
time frame: Average of 12 months
description: Change in bone mineral density of the femoral neck, forearm and spine.
measure: Change in biochemical myeloma markers
time frame: Average of 3 months
description: The change in myeloma markers will be determined by quantifying immunoglobulins, SPEP, UPEP and free light chains.
measure: Size of target bone lesions
time frame: Average of 6 months
description: Measure the change in size of target bone lesions using x-ray of target skeletal lesions.
arm group label: Sotatercept
arm group type: Experimental
description: Sotatercept 0.2 mg/kg will be administered every 21 days for 12 doses subcutaneously into the upper arm, abdomen or thigh.
arm group label: Placebo
arm group type: Placebo Comparator
description: 0.2 mg/kg of normal saline will be administered subcutaneously in the upper arm, abdomen or thigh for 21 days for 12 doses.
intervention type: Drug
intervention name: Sotatercept
arm group label: Sotatercept
other name: ACE-011
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
other name: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rebecca Silbermann, M.D.
role: Principal Investigator
affiliation: Indiana University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Indiana University
investigator full name: Rebecca Silbermann
investigator title: Assistant Professor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell