<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/NCT04435158</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1222-102</org_study_id>
    <nct_id>NCT04435158</nct_id>
  </id_info>
  <brief_title>A Multiple Dose Study to Evaluate the Effect of SHR-1222 Injection in Postmenopausal Osteoporosis Patients</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity Study Following Multiple Subcutaneous Injections of SHR-1222 in Postmenopausal Osteoporosis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Multi-Center, Randomized, Double-Blind, Dose Escalation, Placebo Parallel&#xD;
      Controlled PhaseⅠClinical study to Evaluate the Safety, Tolerability and Pharmacokinetics,&#xD;
      Pharmacodynamics, Immunogenicity with Multiple Subcutaneous Injections of SHR-1222 in&#xD;
      Postmenopausal Osteoporosis Patients.&#xD;
&#xD;
      The primary objective of this study is to investigate the safety and tolerability of a range&#xD;
      of subcutaneous SHR-1222 in postmenopausal osteoporosis patients. Secondary objectives are to&#xD;
      determine the pharmacokinetics (PK), pharmacodynamics (PD) profile of SHR-1222 in&#xD;
      postmenopausal osteoporosis patients including assessment of immunogenicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 25, 2020</start_date>
  <completion_date type="Actual">July 18, 2022</completion_date>
  <primary_completion_date type="Actual">July 18, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerance: Number of subjects with adverse events</measure>
    <time_frame>Dose administration to 225 days after first dose administration</time_frame>
    <description>Number &amp; proportion of subjects with adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter-time to maximum concentration (Tmax)</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter-maximum concentration (Cmax)</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter-area under curve (AUC)</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in osteocalcin from baseline</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in serum totol sclerostin</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4) from baseline by dualenergy X-ray absorptiometry</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in areal bone mineral density of collum femoris from baseline by dualenergy X-ray absorptiometry</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PD parameter-change in areal bone mineral density of total hip from baseline by dualenergy X-ray absorptiometry</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antidrug antibody</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutralizing Antibody</measure>
    <time_frame>Pre-dose to 225 days after first dose administration</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Osteoporosis</condition>
  <arm_group>
    <arm_group_label>Cohort 1：SHR-1222</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection of SHR-1222 dosage 1 monthly × 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2：SHR-1222</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection of SHR-1222 dosage 2 monthly × 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3：SHR-1222</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection of SHR-1222 dosage 3 monthly × 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4：SHR-1222</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection of SHR-1222 dosage 4 every 2 months × 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5：SHR-1222</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection of SHR-1222 dosage 5 every 2 months × 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 6：placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subcutaneous injection of placebo × 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR-1222</intervention_name>
    <description>Pharmaceutical form: water injection Route of administration: subcutaneous injection</description>
    <arm_group_label>Cohort 1：SHR-1222</arm_group_label>
    <arm_group_label>Cohort 2：SHR-1222</arm_group_label>
    <arm_group_label>Cohort 3：SHR-1222</arm_group_label>
    <arm_group_label>Cohort 4：SHR-1222</arm_group_label>
    <arm_group_label>Cohort 5：SHR-1222</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Pharmaceutical form: water injection Route of administration: subcutaneous injection</description>
    <arm_group_label>Cohort 6：placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent;&#xD;
&#xD;
          2. Age ≥50 and ≤70 years old and post menopause for at least 5 years at the time of&#xD;
             screening;&#xD;
&#xD;
          3. Weight ≥40kg at the time of screening;&#xD;
&#xD;
          4. BMD T-score ≤ -2.50 at the lumbar vertebrae, total hip or femoral neck at the time of&#xD;
             screening, based on DXA scans;&#xD;
&#xD;
          5. At least 2 vertebrae in the L1-L4 region and at least one hip are evaluable by DXA;&#xD;
&#xD;
          6. Without disease that would significantly affect the study or bring additional health&#xD;
             risks at the time of screening or baseline; blood pressure &lt; 150 / 95mmHg, blood&#xD;
             fasting blood glucose &lt; 7.0mmol/l, glycosylated hemoglobin &lt; 7%, or total cholesterol&#xD;
             &lt; 6.2mmol/l, triglyceride &lt; 3.4mmol/l under the condition of lifestyle improvement&#xD;
             rather than drug treatment; If there are other abnormalities in the examination report&#xD;
             of the subject, the subject could only be included after investigator approval;&#xD;
&#xD;
          7. Ambulatory.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any disease affecting bone metabolism;&#xD;
&#xD;
          2. Any severe (SQ3) or more than 2 moderate (SQ2) vertebral fractures, as assessed by the&#xD;
             central imaging based on lateral spine x-rays at the time of screening;&#xD;
&#xD;
          3. History of hip fracture;&#xD;
&#xD;
          4. 25 (OH) vitamin D levels &lt; 20 ng/mL at the time of screening. Vitamin D repletion will&#xD;
             be permitted and subjects may be rescreened;&#xD;
&#xD;
          5. BMD T-score &lt; -3.50 at the lumber vertebra, total hip or femoral neck at the time of&#xD;
             screening, based on DXA scans;&#xD;
&#xD;
          6. Use of the following agents affecting bone metabolism:&#xD;
&#xD;
               -  IV bisphosphonates or denosumab prior to screening;&#xD;
&#xD;
               -  Oral bisphosphonates, PTH analogs, Strontium or fluoride within 12m prior to&#xD;
                  screening;&#xD;
&#xD;
               -  Hormone replacement therapy within 6m prior to screening;&#xD;
&#xD;
               -  Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2&#xD;
                  weeks before the enrollment date are allowed), Anabolic steroids, Calcitriol and&#xD;
                  available analogues, thiazide diuretics within 3m prior to screening;&#xD;
&#xD;
          7. History of metabolic or bone disease (except osteoporosis) that may interfere with the&#xD;
             interpretation of the results, such as hyperprolactinemia, osteosclerosis, Paget's&#xD;
             disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis,&#xD;
             ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption&#xD;
             syndrome;&#xD;
&#xD;
          8. Hyperparathyroidism, hypothyroidism, hyperthyroidism, hypothyroidism, hypercalcemia,&#xD;
             hypocalcemia, renal failure, etc at the time of screening;&#xD;
&#xD;
          9. Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in&#xD;
             situ within the last 5 years;&#xD;
&#xD;
         10. A clinical history of drug allergy or a history of atopic allergic diseases (asthma,&#xD;
             urticaria, eczema dermatitis) or a known allergy to experimental or similar&#xD;
             experimental drugs;&#xD;
&#xD;
         11. Past medical history of cerebral infarction, ischemic or hemorrhagic stroke;&#xD;
&#xD;
         12. Past medical history of Myocardial infarction, coronary heart disease, angina&#xD;
             pectoris, heart failure (cardiac function II-IV), serious arrhythmia (such as atrial&#xD;
             fibrillation, pacemaker needed)&#xD;
&#xD;
         13. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic&#xD;
             acyl transferase (GGT) or total bilirubin, more than 2 x ULN during screening;&#xD;
&#xD;
         14. 3 months prior to screening involved in any drug clinical subjects (except screening&#xD;
             failed or not given cinical drugs) or within 5 half-lives of test drug at the time of&#xD;
             screening;&#xD;
&#xD;
         15. Any major surgery in 1m prior to screening or a surgery plan during the study;&#xD;
&#xD;
         16. Blood donation or loss more than 400mL or blood transfusion within 3 months prior to&#xD;
             screening;&#xD;
&#xD;
         17. Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination,&#xD;
             hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were&#xD;
             positive;&#xD;
&#xD;
         18. No history of alcohol and substance abuse or positive urine drug screening;&#xD;
&#xD;
         19. Subjects with any other situation should not be involved, which determined by the&#xD;
             researchers.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhiguang Zhou</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Xiangya Hospital of Central South University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>2nd Xiangya Hospital , Chinese Academy of Medical Sciences</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>July 3, 2023</last_update_submitted>
  <last_update_submitted_qc>July 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 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>Osteoporosis</mesh_term>
    <mesh_term>Osteoporosis, Postmenopausal</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04435158
org study id: SHR-1222-102
nct id: NCT04435158
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a Multi-Center, Randomized, Double-Blind, Dose Escalation, Placebo Parallel
      Controlled PhaseⅠClinical study to Evaluate the Safety, Tolerability and Pharmacokinetics,
      Pharmacodynamics, Immunogenicity with Multiple Subcutaneous Injections of SHR-1222 in
      Postmenopausal Osteoporosis Patients.

      The primary objective of this study is to investigate the safety and tolerability of a range
      of subcutaneous SHR-1222 in postmenopausal osteoporosis patients. Secondary objectives are to
      determine the pharmacokinetics (PK), pharmacodynamics (PD) profile of SHR-1222 in
      postmenopausal osteoporosis patients including assessment of immunogenicity.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety and Tolerance: Number of subjects with adverse events
time frame: Dose administration to 225 days after first dose administration
description: Number & proportion of subjects with adverse events
measure: Assessment of PK parameter-time to maximum concentration (Tmax)
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PK parameter-maximum concentration (Cmax)
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PK parameter-area under curve (AUC)
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in serum C-telopeptide (sCTx) from baseline
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in aminoterminal propeptide type-1 procollagen (P1NP) from baseline
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in osteocalcin from baseline
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in bone-specific alkaline phosphatase (BSAP) from baseline
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in serum totol sclerostin
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in areal bone mineral density of lumbar spine (L1-L4) from baseline by dualenergy X-ray absorptiometry
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in areal bone mineral density of collum femoris from baseline by dualenergy X-ray absorptiometry
time frame: Pre-dose to 225 days after first dose administration
measure: Assessment of PD parameter-change in areal bone mineral density of total hip from baseline by dualenergy X-ray absorptiometry
time frame: Pre-dose to 225 days after first dose administration
measure: Antidrug antibody
time frame: Pre-dose to 225 days after first dose administration
measure: Neutralizing Antibody
time frame: Pre-dose to 225 days after first dose administration
arm group label: Cohort 1：SHR-1222
arm group type: Experimental
description: Subcutaneous injection of SHR-1222 dosage 1 monthly × 6 months
arm group label: Cohort 2：SHR-1222
arm group type: Experimental
description: Subcutaneous injection of SHR-1222 dosage 2 monthly × 6 months
arm group label: Cohort 3：SHR-1222
arm group type: Experimental
description: Subcutaneous injection of SHR-1222 dosage 3 monthly × 6 months
arm group label: Cohort 4：SHR-1222
arm group type: Experimental
description: Subcutaneous injection of SHR-1222 dosage 4 every 2 months × 6 months
arm group label: Cohort 5：SHR-1222
arm group type: Experimental
description: Subcutaneous injection of SHR-1222 dosage 5 every 2 months × 6 months
arm group label: Cohort 6：placebo
arm group type: Experimental
description: Subcutaneous injection of placebo × 6 months
intervention type: Drug
intervention name: SHR-1222
description: Pharmaceutical form: water injection Route of administration: subcutaneous injection
arm group label: Cohort 1：SHR-1222
arm group label: Cohort 2：SHR-1222
arm group label: Cohort 3：SHR-1222
arm group label: Cohort 4：SHR-1222
arm group label: Cohort 5：SHR-1222
intervention type: Drug
intervention name: Placebo
description: Pharmaceutical form: water injection Route of administration: subcutaneous injection
arm group label: Cohort 6：placebo
criteria: 
gender: Female
minimum age: 50 Years
maximum age: 70 Years
healthy volunteers: No
last name: Zhiguang Zhou
role: Principal Investigator
affiliation: 2nd Xiangya Hospital of Central South University
facility: 
country: China
responsible party type: Sponsor
mesh term: Osteoporosis
mesh term: Osteoporosis, Postmenopausal
sharing ipd: Undecided