<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/NCT03242512</url>
  </required_header>
  <id_info>
    <org_study_id>TK006-101</org_study_id>
    <nct_id>NCT03242512</nct_id>
  </id_info>
  <brief_title>Assessment of Anti-RANKL Antibody in Post-menopausal Women</brief_title>
  <official_title>Phase I Trial of Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Fully Human Monoclonal Antibody to RANKL (TK006) in Post-menopausal Women.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu T-Mab Biopharma Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu T-Mab Biopharma Co.,Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-center, open-label, dose-escalating study to evaluate the safety,&#xD;
      pharmacokinetics, immunogenicity, and preliminary efficacy of single dose subcutaneous&#xD;
      injection of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B&#xD;
      ligand (RNAKL) (code name: TK006) in postmenopausal women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I, open-label, single-dose, dose escalation study in postmenopausal women&#xD;
      conducted at single center.&#xD;
&#xD;
      The objectives are to assess the safety and tolerability, effects on bone turnover measured&#xD;
      by biochemical markers and bone density, and the pharmacokinetics and immunogenicity of a&#xD;
      fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL),&#xD;
      (code name: TK006).&#xD;
&#xD;
      Subjects would sequentially enroll in one of three cohorts. Subjects in the first cohort&#xD;
      would receive a single 30-mg subcutaneous injection of TK006. If no safety signals are&#xD;
      observed in the first cohort after 28 days, subjects would enroll in the second cohort and&#xD;
      receive a single 60-mg subcutaneous injection of TK006. After an 28-day period for&#xD;
      observation of safety of the second dose, subjects would enroll in the third cohort and&#xD;
      receive a single 120-mg subcutaneous injection of TK006.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">August 7, 2017</start_date>
  <completion_date type="Anticipated">December 30, 2018</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events （AEs）</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Calculated by the linear trapezoidal method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Calculated by the linear trapezoidal and extrapolation method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed maximum plasma concentration [Cmax]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>The maximum (or peak) serum concentration that TK006 achieves after the drug has been administrated and before the administration of a second dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach the maximum observed plasma concentration [Tmax]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>The time at which the Cmax is observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life[T1/2]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>The time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>The apparent volume of the central compartment cleared of drug per unit time was estimated using the formula: Cl/F = Dose / AUC0-∞</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability corrected apparent volume of distribution [Vd/F]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Apparent volume of distribution based on the terminal elimination phase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum type I collagen cross-link C telopeptide (sNTX)</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum bone alkaline phosphatase [bALP]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Would be assessed at week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intact Parathyroid Hormone (iPTH)</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone density of lumbar vertebra and collum femoris</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Assessed by Dual energy X-ray (DXA) bone density measurement at week 8,16, 24 and 36.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-drug antibody [ADA]</measure>
    <time_frame>Up to 252 days.</time_frame>
    <description>Assessed at day 0（pre-dosing）, week 4, 12, 24 and 36.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Osteoporosis</condition>
  <arm_group>
    <arm_group_label>30 mg single dose cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects would receive a 30 mg single dose of TK006.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>60 mg single dose cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects would receive a 60 mg single dose of TK006.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>120 mg single dose cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects would receive a 120 mg single dose of TK006.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TK006</intervention_name>
    <description>Subcutaneous injection</description>
    <arm_group_label>120 mg single dose cohort</arm_group_label>
    <arm_group_label>30 mg single dose cohort</arm_group_label>
    <arm_group_label>60 mg single dose cohort</arm_group_label>
    <other_name>fully human monoclonal anti-RANKL antibody</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects who provide informed consent voluntarily;&#xD;
&#xD;
          2. Women who are postmenopausal defined as being amenorrheic for at least 24-month, and&#xD;
             follicule-stimulating hormone (FSH)&gt;40 U/L, estradiol (E2)&lt;110pmol/L (or &lt;30pg/mL) as&#xD;
             well;&#xD;
&#xD;
          3. ≤65 years old, with no restricted activity.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known hypersensitivity to similar medicines or other products derived from mammalian&#xD;
             cells, or medical history of severe allergic to foods or medicines;&#xD;
&#xD;
          2. Treatment with diphosphonate or fluoride, oestrogen, selective estrogen receptor&#xD;
             modulators, calcitonin, parathyroid hormone, high dose Vitamin D (≥1000 IU/day),&#xD;
             anabolic steroids, systemic glucocorticoids within 12-month before dosing, or&#xD;
             administered with calcitriol within 6 months before dosing;&#xD;
&#xD;
          3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &gt;2.0 times the&#xD;
             upper limit of normal (ULN), or alkaline phosphatase (ALP)&gt;1.5×ULN, or Total bilirubin&#xD;
             (TBIL) &gt;1.5×ULN, creatinine clearance rate&lt;60 mL/min;&#xD;
&#xD;
          4. Disorders that could affect the study outcomes, such as osteomalacia, dysostosis,&#xD;
             Paget's disease, Cushing syndrome, hyperprolactinemia, rheumatoid arthritis,&#xD;
             hyperparathyroidism, hypoparathyroidism, or other diseases that could affect bone&#xD;
             metabolism;&#xD;
&#xD;
          5. Hyperthyroidism or hypothyroidism, unless hypothyroidism patients are receiving&#xD;
             regular treatment with thyroid hormone and:&#xD;
&#xD;
               -  Thyroid stimulating hormone (TSH) is normal, or&#xD;
&#xD;
               -  TSH&gt;4.78μIU/Ml, ≤10.0μIU/mL and thyroxine (T4) is normal.&#xD;
&#xD;
          6. Malabsorption syndrome or other disorders that could affect intestinal absorption&#xD;
             function, such as Crohn's disease, chronic pancreatitis, etc;&#xD;
&#xD;
          7. Hepatocirrhosis or severe liver disease (defined as ascites, hepatic encepalopathy,&#xD;
             coagulation disorder, hypoalbuminemia, Esophagus and fundus gastricus varication,&#xD;
             persistent jaundice), known diseases of biliary tract (excluding Gilbert syndrome and&#xD;
             Asymptomatic gallstone);&#xD;
&#xD;
          8. Past or currently suffering from mandibular osteomyelitis or osteonecrosis, or any&#xD;
             fracture within 6 months prior to first dosing; or suffering from acute tooth or&#xD;
             mandibular disease that require tooth extracting, dental implanting or other invasive&#xD;
             surgery; or had the above operation within 1-month before first dosing; or unhealing&#xD;
             wound of oral surgery;&#xD;
&#xD;
          9. HBsAg positive, or anti-HCV antibody positive, or anti-HIV antibody positive, or&#xD;
             anti-Syphilis antibody positive;&#xD;
&#xD;
         10. Prior malignancies (excluding the targeted breast cancer, basal cell carcinoma, or&#xD;
             cervical cancer in situ) within 5 years (excluding completely resected Basal cell or&#xD;
             squamous-cell carcinoma in situ, cervical carcinoma and Breast ductal carcinoma；&#xD;
&#xD;
         11. A variety of diseases that affect the ability of the subject to sign informed consent&#xD;
             or follow the steps of the study; or suffer from various physical or mental illnesses&#xD;
             that the investigators consider to affect the subject's successful completion of the&#xD;
             study or may interfere with the interpretation of the findings;&#xD;
&#xD;
         12. Albumin-adjusted calcium≥2.0mmol/L, ≤2.9mmol/ L(Calcium supplements are not allowed&#xD;
             within 8 hours before examination);&#xD;
&#xD;
         13. Subjects with fracture high risk and requiring treatment;&#xD;
&#xD;
         14. Has been selected for the study of other test devices or test drugs, or the duration&#xD;
             of the clinical studies that have taken less than 30 days or 5 half-lives or&#xD;
             biological effects, whichever is longer.&#xD;
&#xD;
         15. Other situations which are not suitable for participation judged by the principal&#xD;
             investigator (PI).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jiang H Y</last_name>
    <role>Study Director</role>
    <affiliation>Jiangsu T-Mab Biopharma Co.,Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>March 13, 2018</last_update_submitted>
  <last_update_submitted_qc>March 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RANKL</keyword>
  <keyword>osteoporosis</keyword>
  <keyword>bone resorption</keyword>
  <keyword>post-menopausal women</keyword>
  <keyword>TK006</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</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/NCT03242512
org study id: TK006-101
nct id: NCT03242512
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a single-center, open-label, dose-escalating study to evaluate the safety,
      pharmacokinetics, immunogenicity, and preliminary efficacy of single dose subcutaneous
      injection of a fully human monoclonal antibody of receptor activator for nuclear factor-κ B
      ligand (RNAKL) (code name: TK006) in postmenopausal women.
This is a phase I, open-label, single-dose, dose escalation study in postmenopausal women
      conducted at single center.

      The objectives are to assess the safety and tolerability, effects on bone turnover measured
      by biochemical markers and bone density, and the pharmacokinetics and immunogenicity of a
      fully human monoclonal antibody of receptor activator for nuclear factor-κ B ligand (RNAKL),
      (code name: TK006).

      Subjects would sequentially enroll in one of three cohorts. Subjects in the first cohort
      would receive a single 30-mg subcutaneous injection of TK006. If no safety signals are
      observed in the first cohort after 28 days, subjects would enroll in the second cohort and
      receive a single 60-mg subcutaneous injection of TK006. After an 28-day period for
      observation of safety of the second dose, subjects would enroll in the third cohort and
      receive a single 120-mg subcutaneous injection of TK006.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events （AEs）
time frame: Up to 252 days.
description: Include physical findings, changes in laboratory values, vital signs, and 12-lead electrocardiogram (ECG) data.
measure: Area under the plasma concentration-time curve from time zero to time 'last' where last is the last time point after administration [AUClast]
time frame: Up to 252 days.
description: Calculated by the linear trapezoidal method.
measure: Area under the plasma concentration-time curve from time zero to infinity [AUC0-inf]
time frame: Up to 252 days.
description: Calculated by the linear trapezoidal and extrapolation method.
measure: Maximum observed maximum plasma concentration [Cmax]
time frame: Up to 252 days.
description: The maximum (or peak) serum concentration that TK006 achieves after the drug has been administrated and before the administration of a second dose.
measure: Time to reach the maximum observed plasma concentration [Tmax]
time frame: Up to 252 days.
description: The time at which the Cmax is observed.
measure: Terminal elimination half-life[T1/2]
time frame: Up to 252 days.
description: The time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.
measure: Bioavailability corrected apparent volume of the central compartment cleared of drug per unit [Cl/F]
time frame: Up to 252 days.
description: The apparent volume of the central compartment cleared of drug per unit time was estimated using the formula: Cl/F = Dose / AUC0-∞
measure: Bioavailability corrected apparent volume of distribution [Vd/F]
time frame: Up to 252 days.
description: Apparent volume of distribution based on the terminal elimination phase.
measure: Serum type I collagen cross-link C telopeptide (sNTX)
time frame: Up to 252 days.
description: Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
measure: serum bone alkaline phosphatase [bALP]
time frame: Up to 252 days.
description: Would be assessed at week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
measure: Intact Parathyroid Hormone (iPTH)
time frame: Up to 252 days.
description: Would be assessed at day1, 3, week 1, 2, 4, 8, 12, 16, 20, 24, 28, 32 and 36.
measure: Bone density of lumbar vertebra and collum femoris
time frame: Up to 252 days.
description: Assessed by Dual energy X-ray (DXA) bone density measurement at week 8,16, 24 and 36.
measure: anti-drug antibody [ADA]
time frame: Up to 252 days.
description: Assessed at day 0（pre-dosing）, week 4, 12, 24 and 36.
arm group label: 30 mg single dose cohort
arm group type: Experimental
description: Subjects would receive a 30 mg single dose of TK006.
arm group label: 60 mg single dose cohort
arm group type: Experimental
description: Subjects would receive a 60 mg single dose of TK006.
arm group label: 120 mg single dose cohort
arm group type: Experimental
description: Subjects would receive a 120 mg single dose of TK006.
intervention type: Biological
intervention name: TK006
description: Subcutaneous injection
arm group label: 120 mg single dose cohort
arm group label: 30 mg single dose cohort
arm group label: 60 mg single dose cohort
other name: fully human monoclonal anti-RANKL antibody
criteria: 
gender: Female
minimum age: N/A
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jiang H Y
role: Study Director
affiliation: Jiangsu T-Mab Biopharma Co.,Ltd
facility: 
country: China
responsible party type: Sponsor
mesh term: Osteoporosis