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/NCT05972551</url>
    </required_header>
    <id_info>
      <org_study_id>20200105</org_study_id>
      <secondary_id>2023-503294-37</secondary_id>
      <nct_id>NCT05972551</nct_id>
    </id_info>
    <brief_title>Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta</brief_title>
    <official_title>A Phase 3, Open-Label, Multicenter, Randomized Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Amgen</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Amgen</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>
        The primary objective of this study is to evaluate the effect of romosozumab treatment for&#xD;
        12-months compared with bisphosphonate(s) on the number of clinical fractures at 12-months;&#xD;
        the number of any fractures at 12-months and change in lumbar spine bone mineral density&#xD;
        (BMD) Z-score at 6-months.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 23, 2023</start_date>
    <completion_date type="Anticipated">July 9, 2027</completion_date>
    <primary_completion_date type="Anticipated">April 5, 2027</primary_completion_date>
    <phase>Phase 3</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of Clinical Fractures</measure>
      <time_frame>12 months</time_frame>
      <description>Clinical fractures include clinical vertebral fractures and nonvertebral fractures.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Any Fractures</measure>
      <time_frame>12 months</time_frame>
      <description>Fractures include new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral fractures.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from Baseline to 6 Months in Lumbar Spine BMD Z-score</measure>
      <time_frame>Baseline and 6 months</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline to 12 Months in Lumbar Spine BMD Z-score</measure>
      <time_frame>Baseline and 12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline to 6 Months in Total Hip BMD Z-score</measure>
      <time_frame>Baseline and 6 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline to 12 Months in Total Hip BMD Z-score</measure>
      <time_frame>Baseline and 12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline to 6 Months in Femoral Neck BMD Z-score</measure>
      <time_frame>Baseline and 6 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline to 12 Months in Femoral Neck BMD Z-score</measure>
      <time_frame>Baseline and 12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Any Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Clinical Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with New or Worsening Vertebral Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Nonvertebral Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of New or Worsening Vertebral Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Nonvertebral Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Long Bone Fractures</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score</measure>
      <time_frame>Baseline and 12 months</time_frame>
      <description>The CHQ-PF-50 measures how a child's condition affects their ability to function in daily life. The CHQ-PF-50 measures 50 items in the following domains: physical functioning, role/social limitations - physical, general health perceptions, bodily pain/discomfort, family activities, role/social limitations - emotional/behavioral, parent impact - time, parent impact - emotion, self-esteem, mental health, behavior, family cohesion, change in health.&#xD;
  Each item is rated on a scale from &quot;without any difficulty&quot; to &quot;unable to do&quot;. Total scores for each item are transformed to 0 - 100 scale, with lower scores indicating worse health states. Higher change from baseline scores indicate better or more positive health states.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ-CV) Disability Score</measure>
      <time_frame>Baseline and 12 months</time_frame>
      <description>The CHAQ-CV measures how a child's condition affects their ability to function in daily life. The CHAQ-CV measures 50 items in the following domains: physical functioning, role/social limitations - physical, general health perceptions, bodily pain/discomfort, family activities, role/social limitations emotional/behavioral, self-esteem, mental health, behavior, family cohesion, change in health.&#xD;
  Each item is rated on a scale from &quot;without any difficulty&quot; to &quot;unable to do&quot;. Total scores for each item are transformed to 0 - 100 scale, with lower scores indicating worse health states. Higher change from baseline scores indicate better or more positive health states.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from Baseline in the Wong-Baker Faces Pain Rating Scale</measure>
      <time_frame>Baseline and 12 months</time_frame>
      <description>The Wong-Baker Faces Pain Rating Scale is a horizontal pain scale that consists of six hand-drawn faces that range from a smiling &quot;no hurt&quot; face with a score of 0 to a crying &quot;hurts worst&quot; face with a score of 10. Greater change from baseline scores indicate greater pain experienced by the participant.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum Concentration of Romosozumab</measure>
      <time_frame>Day 1 to Month 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months</measure>
      <time_frame>12 months</time_frame>
      <description>Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Anti-romosozumab Antibodies at 12 Months</measure>
      <time_frame>12 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants who Experience TEAEs from Month 12 to Month 15</measure>
      <time_frame>Month 12 to Month 15</time_frame>
      <description>Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Anti-romosozumab Antibodies from Month 12 to Month 15</measure>
      <time_frame>Month 12 to Month 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants who Experience TEAEs at 15 Months</measure>
      <time_frame>15 months</time_frame>
      <description>Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with Anti-romosozumab Antibodies at 15 Months</measure>
      <time_frame>15 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull</measure>
      <time_frame>Baseline and 6 months</time_frame>
      <description>Measured in a subset of participants who receive cranial nerve computerized tomography (CT) scans.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull</measure>
      <time_frame>Baseline and 12 months</time_frame>
      <description>Measured in a subset of participants who receive cranial nerve CT scans.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">106</enrollment>
    <condition>Osteogenesis Imperfecta</condition>
    <arm_group>
      <arm_group_label>Romosozumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive romosozumab once a month (QM) for 12 months.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard of Care Bisphosphonate</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will receive bisphosphonates per local standard of care treatment regimens, as determined by the investigator for 12 months.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Romosozumab</intervention_name>
      <description>Subcutaneous (SC) injection</description>
      <arm_group_label>Romosozumab</arm_group_label>
      <other_name>EVENITY®</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bisphosphonate</intervention_name>
      <description>Administration determined by investigator according to the local standard of care</description>
      <arm_group_label>Standard of Care Bisphosphonate</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participant has provided informed consent/assent prior to initiation of any study&#xD;
               specific activities/procedures.&#xD;
  &#xD;
          OR&#xD;
  &#xD;
            -  Participant's legally authorized representative has provided informed consent when the&#xD;
               participant is legally too young to provide informed consent and the participant has&#xD;
               provided written assent based on local regulations and/or guidelines prior to any&#xD;
               study-specific activities/procedures being initiated.&#xD;
  &#xD;
            -  Ambulatory male and female children and adolescents, age 5 to &lt;18 years, including&#xD;
               ambulatory with assistance as defined in the pediatric osteogenesis imperfecta (OI)&#xD;
               population.&#xD;
  &#xD;
            -  Clinical diagnosis of OI, defined as clinical history consistent with type I, III, or&#xD;
               IV OI as determined by presence of expected phenotype (examples include: facial shape,&#xD;
               voice, blue sclera, dentinogenesis imperfecta, typical radiographic features, fracture&#xD;
               pattern) and lack of additional features unrelated to type I, III, or IV OI (eg,&#xD;
               blindness, mental retardation, neuropathy, and craniosynostosis).&#xD;
  &#xD;
               o If familial, also must be autosomal dominant.&#xD;
  &#xD;
            -  Meets at least one of the following:&#xD;
  &#xD;
                 -  3 or more fractures within the previous 2 years, or&#xD;
  &#xD;
                 -  1 or more nonvertebral fracture(s) within the previous 2 years and at least 1&#xD;
                    prevalent vertebral fracture, or&#xD;
  &#xD;
                 -  2 or more prevalent vertebral fractures.&#xD;
  &#xD;
            -  Lumbar spine Z-score of ≤-1.0.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Disease Related&#xD;
  &#xD;
            -  History of an electrophoresis pattern inconsistent with type I, III or IV OI.&#xD;
  &#xD;
            -  History of known mutation in a gene other than collagen type I alpha 1/collagen type I&#xD;
               alpha 2 (COL1A1/COL1A2) causing OI or other metabolic bone disease.&#xD;
  &#xD;
            -  History of congenital dislocation of the radial head, interosseous membrane&#xD;
               calcification, or exuberant callus formation.&#xD;
  &#xD;
          Other Medical Conditions&#xD;
  &#xD;
            -  History of osteomalacia or rickets.&#xD;
  &#xD;
            -  Body weight less than 10 kg or greater than 90 kg.&#xD;
  &#xD;
            -  History of other bone diseases that affect bone metabolism (e.g., osteoporosis&#xD;
               pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis,&#xD;
               hypophosphatasia).&#xD;
  &#xD;
            -  History of Kawasaki disease, rheumatic myocarditis, ischemic cardiomyopathy, inherited&#xD;
               cardiomyopathies, nephrotic syndrome, familial hypercholesterolemia, stroke, or any&#xD;
               thromboembolic disorder.&#xD;
  &#xD;
            -  Evidence of untreated or unhealed oral infections.&#xD;
  &#xD;
            -  Unhealed or planned invasive dental or tooth procedure as determined by treating&#xD;
               dentist; removal of baby teeth is acceptable and not considered an invasive dental&#xD;
               procedure.&#xD;
  &#xD;
            -  Unhealed fracture as defined by orthopedic opinion.&#xD;
  &#xD;
            -  Osteotomy, rodding surgery or spinal fusion surgery within 5-months prior to&#xD;
               screening, or not yet healed per orthopedic surgeon.&#xD;
  &#xD;
            -  History of clinically significant valvular heart disease previously documented with&#xD;
               local echocardiogram results.&#xD;
  &#xD;
            -  Evidence of any of the following:&#xD;
  &#xD;
                 -  Current hyper- or hypoparathyroidism (parathyroid hormone outside the normal&#xD;
                    range).&#xD;
  &#xD;
                 -  Renal disease: Estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m^2&#xD;
                    (calculated by the bedside Schwartz equation at screening) eGFR (mL/min/1.73 m^2)&#xD;
                    = 0.413 X (height/serum creatinine)&#xD;
  &#xD;
                    1. (Height is in centimeters, and serum creatinine is in mg/dL).&#xD;
  &#xD;
                 -  Current hypocalcemia (albumin-adjusted serum calcium &lt;lower limit of normal&#xD;
                    [LLN]) or hypercalcemia (albumin-adjusted serum calcium &gt; upper limit of normal&#xD;
                    [ULN] of the laboratory's reference range).&#xD;
  &#xD;
                 -  Serum vitamin D &lt;20 ng/mL; rescreening for Vitamin D level &lt; 20 ng/mL will be&#xD;
                    allowed, after adequate supplementation.&#xD;
  &#xD;
                 -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) &gt; 1.5 x ULN.&#xD;
  &#xD;
                 -  Total bilirubin (TBL) &gt;1.5 x ULN (participants with Gilbert syndrome are&#xD;
                    eligible).&#xD;
  &#xD;
                 -  Serum phosphorus &lt; LLN for age.&#xD;
  &#xD;
            -  Symptoms associated with skull abnormalities such as basilar invagination, basilar&#xD;
               impression or Chiari malformation (e.g., headache induced by coughing or straining for&#xD;
               stool, visual disturbances, paresthesias or weakness).&#xD;
  &#xD;
            -  History of malabsorption (in children with serum albumin &lt;LLN, malabsorption should be&#xD;
               clinically ruled out by the investigator to confirm eligibility).&#xD;
  &#xD;
            -  History of long QT syndrome.&#xD;
  &#xD;
            -  History of malignancy.&#xD;
  &#xD;
            -  History of any solid organ or bone marrow transplant.&#xD;
  &#xD;
            -  History of hyper- or hypothyroidism, unless participant is on stable therapy &gt;&#xD;
               6-months and has supporting laboratory documentation within 6-months prior to or at&#xD;
               screening indicating normal serum thyroid-stimulating hormone (TSH) value.&#xD;
  &#xD;
            -  Known intolerance to calcium or vitamin D supplements.&#xD;
  &#xD;
          Prior/Concomitant Therapy&#xD;
  &#xD;
            -  Prior treatment with:&#xD;
  &#xD;
            -  Romosozumab or other anti-sclerostin antibody within 12-months prior to screening.&#xD;
  &#xD;
            -  Fluoride or strontium for bone disease.&#xD;
  &#xD;
            -  Parathyroid hormone (PTH) or PTH derivatives within 12-months prior to screening.&#xD;
  &#xD;
            -  Denosumab within 12-months after the last injection prior to first dose of&#xD;
               romosozumab.&#xD;
  &#xD;
            -  Administration of any of the following treatments within 3-months prior to screening:&#xD;
  &#xD;
            -  Systemic glucocorticoids (≥ 5.0 mg prednisone equivalent/day for more than 10 days)&#xD;
               within 3-months prior to screening. Topical and inhaled glucocorticoids will be&#xD;
               allowed.&#xD;
  &#xD;
            -  Growth hormone (participants on stable dose of growth hormone for at least 3-months&#xD;
               prior to screening will be allowed).&#xD;
  &#xD;
            -  Calcitonin.&#xD;
  &#xD;
            -  Other bone active drugs including anticonvulsants (except gabapentin and&#xD;
               benzodiazepines) and heparin (unless low molecular weight heparin).&#xD;
  &#xD;
            -  Chronic systemic ketoconazole, androgens (except participants who have received&#xD;
               testosterone therapy for physiologic replacement in the setting of documented hormonal&#xD;
               deficiency), adrenocorticotropic hormone (ACTH), cinacalcet, aluminum, lithium,&#xD;
               protease inhibitors, gonadotropin-releasing hormone agonists.&#xD;
  &#xD;
          Prior/Concurrent Clinical Study Experience&#xD;
  &#xD;
          - Currently receiving treatment in another investigational device or drug study, or less&#xD;
          than 2 years since ending treatment on another investigational device or drug study(ies).&#xD;
          Other investigational procedures while participating in this study are excluded.&#xD;
  &#xD;
          Other Exclusions&#xD;
  &#xD;
            -  Positive blood screen for hepatitis B surface antigen (HbsAg), hepatitis B core&#xD;
               antibody (HBcAb), or hepatitis C antibody (HepCAb), human immunodeficiency virus (HIV)&#xD;
               -1 or -2 antibody. HIV testing to be performed if required by local health&#xD;
               authorities, ethics boards, or based on investigator's judgement.&#xD;
  &#xD;
            -  Less than 2 evaluable vertebrae by dual-energy x-ray absorptiometry evaluation in the&#xD;
               region of interest, L1-L4, as confirmed by the central imaging laboratory.&#xD;
  &#xD;
            -  Any planned major surgery, including skeletal surgery (eg, rodding surgery, spinal&#xD;
               surgery) within the next 12-months from Day 1 that would interfere with study&#xD;
               procedures or would require missing of any investigational product&#xD;
  &#xD;
            -  Female participants of childbearing potential unwilling to use protocol specified&#xD;
               method of contraception during treatment and for an additional 3-months after the last&#xD;
               dose of investigational product or non-investigational product.&#xD;
  &#xD;
            -  Female participants who are breastfeeding or who plan to breastfeed while on study&#xD;
               through 3-months after the last dose of investigational product or non-investigational&#xD;
               product.&#xD;
  &#xD;
            -  Female participants planning to become pregnant or donate eggs while on study through&#xD;
               3-months after the last dose of investigational product or non-investigational&#xD;
               product.&#xD;
  &#xD;
            -  Female participants of childbearing potential with a positive pregnancy test assessed&#xD;
               at Screening and/or Day 1 by a highly sensitive urine or serum pregnancy test.&#xD;
  &#xD;
            -  Male participants with a female partner of childbearing potential who are unwilling to&#xD;
               practice sexual abstinence (refrain from heterosexual intercourse) or use&#xD;
               contraception during treatment and for an additional 3-months after the last dose of&#xD;
               investigational product or non-investigational product.&#xD;
  &#xD;
            -  Male participants unwilling to abstain from donating sperm during treatment and for an&#xD;
               additional 3-months after the last dose of investigational product or&#xD;
               non-investigational product.&#xD;
  &#xD;
            -  Participant has known sensitivity to any of the products to be administered during&#xD;
               dosing.&#xD;
  &#xD;
            -  Participant likely to not be available to complete all protocol-required study visits&#xD;
               or procedures, and/or to comply with all required study procedures (eg, Clinical&#xD;
               Outcome Assessments) to the best of the participant and investigator's knowledge.&#xD;
  &#xD;
            -  History or evidence of any other clinically significant disorder, condition or disease&#xD;
               (with the exception of those outlined above) that, in the opinion of the investigator&#xD;
               or Amgen physician, if consulted, would pose a risk to participant safety or interfere&#xD;
               with the study evaluation, procedures or completion&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>5 Years</minimum_age>
      <maximum_age>17 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>MD</last_name>
      <role>Study Director</role>
      <affiliation>Amgen</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Amgen Call Center</last_name>
      <phone>866-572-6436</phone>
      <email>medinfo@amgen.com</email>
    </overall_contact>
    <link>
      <url>http://www.amgentrials.com</url>
      <description>AmgenTrials clinical trials website</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Osteogenesis Imperfecta</keyword>
    <keyword>Romosozumab</keyword>
    <keyword>EVENITY®</keyword>
    <keyword>Bisphosphonates</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Osteogenesis Imperfecta</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diphosphonates</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.</ipd_time_frame>
      <ipd_access_criteria>Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.</ipd_access_criteria>
      <ipd_url>http://www.amgen.com/datasharing</ipd_url>
    </patient_data>
    <!-- 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/NCT05972551
  org study id: 20200105
  secondary id: 2023-503294-37
  nct id: NCT05972551
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary objective of this study is to evaluate the effect of romosozumab treatment for
        12-months compared with bisphosphonate(s) on the number of clinical fractures at 12-months;
        the number of any fractures at 12-months and change in lumbar spine bone mineral density
        (BMD) Z-score at 6-months.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of Clinical Fractures
  time frame: 12 months
  description: Clinical fractures include clinical vertebral fractures and nonvertebral fractures.
  measure: Number of Any Fractures
  time frame: 12 months
  description: Fractures include new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral fractures.
  measure: Change from Baseline to 6 Months in Lumbar Spine BMD Z-score
  time frame: Baseline and 6 months
  measure: Change from Baseline to 12 Months in Lumbar Spine BMD Z-score
  time frame: Baseline and 12 months
  measure: Change from Baseline to 6 Months in Total Hip BMD Z-score
  time frame: Baseline and 6 months
  measure: Change from Baseline to 12 Months in Total Hip BMD Z-score
  time frame: Baseline and 12 months
  measure: Change from Baseline to 6 Months in Femoral Neck BMD Z-score
  time frame: Baseline and 6 months
  measure: Change from Baseline to 12 Months in Femoral Neck BMD Z-score
  time frame: Baseline and 12 months
  measure: Number of Participants with Any Fractures
  time frame: 12 months
  measure: Number of Participants with Clinical Fractures
  time frame: 12 months
  measure: Number of Participants with New or Worsening Vertebral Fractures
  time frame: 12 months
  measure: Number of Participants with Nonvertebral Fractures
  time frame: 12 months
  measure: Number of New or Worsening Vertebral Fractures
  time frame: 12 months
  measure: Number of Nonvertebral Fractures
  time frame: 12 months
  measure: Number of Long Bone Fractures
  time frame: 12 months
  measure: Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score
  time frame: Baseline and 12 months
  description: The CHQ-PF-50 measures how a child's condition affects their ability to function in daily life. The CHQ-PF-50 measures 50 items in the following domains: physical functioning, role/social limitations - physical, general health perceptions, bodily pain/discomfort, family activities, role/social limitations - emotional/behavioral, parent impact - time, parent impact - emotion, self-esteem, mental health, behavior, family cohesion, change in health.
  Each item is rated on a scale from "without any difficulty" to "unable to do". Total scores for each item are transformed to 0 - 100 scale, with lower scores indicating worse health states. Higher change from baseline scores indicate better or more positive health states.
  measure: Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ-CV) Disability Score
  time frame: Baseline and 12 months
  description: The CHAQ-CV measures how a child's condition affects their ability to function in daily life. The CHAQ-CV measures 50 items in the following domains: physical functioning, role/social limitations - physical, general health perceptions, bodily pain/discomfort, family activities, role/social limitations emotional/behavioral, self-esteem, mental health, behavior, family cohesion, change in health.
  Each item is rated on a scale from "without any difficulty" to "unable to do". Total scores for each item are transformed to 0 - 100 scale, with lower scores indicating worse health states. Higher change from baseline scores indicate better or more positive health states.
  measure: Change from Baseline in the Wong-Baker Faces Pain Rating Scale
  time frame: Baseline and 12 months
  description: The Wong-Baker Faces Pain Rating Scale is a horizontal pain scale that consists of six hand-drawn faces that range from a smiling "no hurt" face with a score of 0 to a crying "hurts worst" face with a score of 10. Greater change from baseline scores indicate greater pain experienced by the participant.
  measure: Serum Concentration of Romosozumab
  time frame: Day 1 to Month 12
  measure: Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months
  time frame: 12 months
  description: Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.
  measure: Number of Participants with Anti-romosozumab Antibodies at 12 Months
  time frame: 12 months
  measure: Number of Participants who Experience TEAEs from Month 12 to Month 15
  time frame: Month 12 to Month 15
  description: Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.
  measure: Number of Participants with Anti-romosozumab Antibodies from Month 12 to Month 15
  time frame: Month 12 to Month 15
  measure: Number of Participants who Experience TEAEs at 15 Months
  time frame: 15 months
  description: Any clinically signification change from baseline in laboratory values and vital signs after first dose will be recorded as a TEAE.
  measure: Number of Participants with Anti-romosozumab Antibodies at 15 Months
  time frame: 15 months
  measure: Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull
  time frame: Baseline and 6 months
  description: Measured in a subset of participants who receive cranial nerve computerized tomography (CT) scans.
  measure: Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull
  time frame: Baseline and 12 months
  description: Measured in a subset of participants who receive cranial nerve CT scans.
  arm group label: Romosozumab
  arm group type: Experimental
  description: Participants will receive romosozumab once a month (QM) for 12 months.
  arm group label: Standard of Care Bisphosphonate
  arm group type: Active Comparator
  description: Participants will receive bisphosphonates per local standard of care treatment regimens, as determined by the investigator for 12 months.
  intervention type: Drug
  intervention name: Romosozumab
  description: Subcutaneous (SC) injection
  arm group label: Romosozumab
  other name: EVENITY®
  intervention type: Drug
  intervention name: Bisphosphonate
  description: Administration determined by investigator according to the local standard of care
  arm group label: Standard of Care Bisphosphonate
  criteria: 
  gender: All
  minimum age: 5 Years
  maximum age: 17 Years
  healthy volunteers: No
  last name: MD
  role: Study Director
  affiliation: Amgen
  last name: Amgen Call Center
  phone: 866-572-6436
  email: medinfo@amgen.com
  url: http://www.amgentrials.com
  description: AmgenTrials clinical trials website
  responsible party type: Sponsor
  mesh term: Osteogenesis Imperfecta
  mesh term: Diphosphonates
  sharing ipd: Yes
  ipd description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
  ipd access criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
  ipd url: http://www.amgen.com/datasharing