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/NCT05974969</url>
    </required_header>
    <id_info>
      <org_study_id>BCD-264-1</org_study_id>
      <nct_id>NCT05974969</nct_id>
    </id_info>
    <brief_title>A Study to Assess the PK, PD, Safety and Immunogenicity of Single IV Infusion of BCD-264 and Darzalex in Healthy Subjects</brief_title>
    <official_title>A Randomized, Double-Blind, Comparative Clinical Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of Single Intravenous Infusion of BCD-264 and Darzalex® in Healthy Volunteers</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Biocad</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Biocad</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>
        The goal of this clinical study is to establish the comparability of the pharmacokinetics and&#xD;
        similarity of the safety, immunogenicity and pharmacodynamic profiles of BCD-264 and Darzalex&#xD;
        following a single intravenous infusion in healthy subjects.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this clinical study, each subject will receive a single intravenous infusion of BCD-264 or&#xD;
        Darzalex, depending on the group the subject will be randomized to. The drugs are&#xD;
        administered at the study site at a dose of 8 mg/kg.&#xD;
  &#xD;
        The subjects will be followed up and blood samples collected for pharmacokinetics,&#xD;
        pharmacodynamics, immunogenicity and safety studies up to and including 71 study days after&#xD;
        the administration of IP.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">May 17, 2023</start_date>
    <completion_date type="Anticipated">August 2023</completion_date>
    <primary_completion_date type="Anticipated">August 2023</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>Other</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Area under the serum concentration-time curve from time 0 to infinity (AUC0-∞)</measure>
      <time_frame>Up to Day 71</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Area under the serum concentration-time curve from time 0 to the last measurable concentration (AUC0-t)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum observed drug concentration (Cmax)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time from administration to maximum observed concentration of the drug (Тmax)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Elimination half-life (Т½)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Elimination rate constant (Кel)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total clearance (Cl)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Volume of distribution (Vd)</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum effect (Emax)</measure>
      <time_frame>Up to Day 71</time_frame>
      <description>Pharmacodynamics will be evaluated based on the absolute count and percentage of CD38+ cells in peripheral blood (T cells, B cells, NK cells, plasmablasts and plasma cells)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to maximum effect (TEmax)</measure>
      <time_frame>Up to Day 71</time_frame>
      <description>Pharmacodynamics will be evaluated based on the absolute count and percentage of CD38+ cells in peripheral blood (T cells, B cells, NK cells, plasmablasts and plasma cells)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and characteristics of adverse events</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects with BAbs/NAbs</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time until the BAb/NAb development</measure>
      <time_frame>Up to Day 71</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">146</enrollment>
    <condition>Healthy</condition>
    <arm_group>
      <arm_group_label>BCD-264</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>INN: daratumumab, single IV infusion at a dose of 8 mg/kg.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Darzalex</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>INN: daratumumab, single IV infusion at a dose of 8 mg/kg.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BCD-264</intervention_name>
      <description>a single intravenous infusion of BCD-264</description>
      <arm_group_label>BCD-264</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Darzalex</intervention_name>
      <description>a single intravenous infusion of Darzalex</description>
      <arm_group_label>Darzalex</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signed informed consent to participate in the study.&#xD;
  &#xD;
            2. Men aged 18-45 years inclusive at the time of signing the Informed Consent Form.&#xD;
  &#xD;
            3. Body mass index (BMI) in the range of 18.5-30.0 kg/m2.&#xD;
  &#xD;
            4. The confirmed &quot;healthy&quot; status based on the conventional clinical and laboratory&#xD;
               assessments and investigations obtained as screening.&#xD;
  &#xD;
            5. Hemodynamic parameters within the normal range: systolic blood pressure (SBP) in the&#xD;
               range of 100-130 mmHg, diastolic (DBP) in the range of 60-90 mmHg, wrist pulse rate&#xD;
               60-90 bpm, obtained at screening.&#xD;
  &#xD;
            6. The ability of the subject to follow the Protocol procedures, according to the&#xD;
               Investigator.&#xD;
  &#xD;
            7. No history of alcoholism abuse or drug addiction and negative test results for&#xD;
               alcohol, psychotropic and narcotic substances, psychoactive drugs at screening and&#xD;
               before IP infusion.&#xD;
  &#xD;
            8. The willingness of subjects, starting from the moment of signing the informed consent&#xD;
               form, during the study and for 3 months after the IP administration, to use condoms&#xD;
               during any sexual contact by penetration with persons of any sex, including pregnant&#xD;
               women. This requirement does not apply to participants who underwent surgical&#xD;
               sterilization (bilateral orchiectomy).&#xD;
  &#xD;
            9. Willingness to refuse to donate sperm and to conceive a child starting from signing&#xD;
               the informed consent form, during the study and for 3 months after the IP&#xD;
               administration.&#xD;
  &#xD;
           10. Willingness to refrain from drinking alcohol a day (24 hours) before the IP&#xD;
               administration and for 96 hours after the administration, and then a day before each&#xD;
               scheduled visit.&#xD;
  &#xD;
           11. Willingness to refrain from smoking within 2 hours before the IP administration and&#xD;
               then 2 hours before each measurement of blood pressure (BP), pulse rate at the wrist,&#xD;
               respiratory rate, blood sampling, ECG.&#xD;
  &#xD;
           12. Willingness to refrain from vaccination with live attenuated vaccines (intranasal&#xD;
               influenza, measles, mumps, rubella, polio, BCG, yellow fever, chickenpox, and typhoid&#xD;
               TY21a vaccines) during the main study period.&#xD;
  &#xD;
           13. Willingness to refrain from taking any medications, including over-the-counter drugs,&#xD;
               vitamins and food supplements, with the exception of drugs prescribed by the&#xD;
               investigator for the treatment of AEs, throughout the study.&#xD;
  &#xD;
           14. Willingness to refrain from donating blood and plasma for 6 months after the IP&#xD;
               administration.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Mental illness or other conditions that may affect the subject's ability to comply&#xD;
               with the Study Protocol.&#xD;
  &#xD;
            2. Any surgery performed less than 30 days before the screening.&#xD;
  &#xD;
            3. Impossibility to insert a venous catheter for blood sampling (for example, due to skin&#xD;
               disease at venipuncture sites).&#xD;
  &#xD;
            4. History of severe hypersensitivity reactions (anaphylaxis or multiple drug allergy).&#xD;
  &#xD;
            5. Known allergy or intolerance to monoclonal antibody products (murine, chimeric,&#xD;
               humanized, and fully human) or any other components of the IP.&#xD;
  &#xD;
            6. Administration and use of the following drugs:&#xD;
  &#xD;
                 -  Regular oral or parenteral administration of any medicinal products, including&#xD;
                    over-the-counter drugs, vitamins, and dietary supplements, within less than 14&#xD;
                    calendar days prior to estimated date of randomization;&#xD;
  &#xD;
                 -  A history of receiving daratumumab and/or other anti-CD38 monoclonal antibodies.&#xD;
  &#xD;
                 -  Taking medications, including over-the-counter drugs that have a pronounced&#xD;
                    effect on hemodynamics and liver function (barbiturates, omeprazole, cimetidine,&#xD;
                    etc.), within less than 30 days before the estimated date of randomization.&#xD;
  &#xD;
                 -  Taking drugs that affect the immune status (cytokines and their inducers,&#xD;
                    glucocorticoids, etc.) within less than 60 days before the estimated date of&#xD;
                    randomization.&#xD;
  &#xD;
                 -  Systemic use of antibacterial, antimycotic, antiviral or antiprotozoal drugs&#xD;
                    within less than 60 days before the estimated date of randomization.&#xD;
  &#xD;
            7. Positive results of screening tests for HIV, hepatitis B and C viruses.&#xD;
  &#xD;
            8. Positive result of indirect antiglobulin test (indirect Coombs test) at screening.&#xD;
  &#xD;
            9. Conventional laboratory parameters or investigations out of the reference ranges&#xD;
               accepted at the study sites.&#xD;
  &#xD;
           10. Chronic diseases of the cardiovascular, bronchopulmonary, and neuroendocrine systems,&#xD;
               as well as diseases of the gastrointestinal tract, kidneys, and blood.&#xD;
  &#xD;
           11. Acute infectious diseases less than 4 weeks before the estimated date of&#xD;
               randomization, as well as chronic and other diseases that, in the Investigator's&#xD;
               opinion, may affect the PK parameters and safety of the IP.&#xD;
  &#xD;
           12. Smoking over 10 cigarettes a day.&#xD;
  &#xD;
           13. Consumption of more than 10 units of alcohol a week (1 unit of alcohol is equivalent&#xD;
               to ½ L of beer, 200 mL of wine or 50 mL of spirits) or a history of alcoholism, drug&#xD;
               addiction, or drug abuse.&#xD;
  &#xD;
           14. Donation of ≥450 mL of blood or plasma within 60 calendar days prior to the expected&#xD;
               date of randomization;&#xD;
  &#xD;
           15. Participation in any clinical studies of medicinal products at the time of signing the&#xD;
               informed consent or less than 30 calendar days before the expected date of&#xD;
               randomization, if the subject received the medicinal product during the clinical&#xD;
               study.&#xD;
  &#xD;
           16. Previous participation in the same study if the subject was randomized and received&#xD;
               the IP during the study.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Institute of the Human Brain n. a. N.P. Bekhtereva Russian Academy of Sciences</name>
        <address>
          <city>Saint Petersburg</city>
          <country>Russian Federation</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Smorodintsev Research Institute of Influenza</name>
        <address>
          <city>Saint Petersburg</city>
          <country>Russian Federation</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>X7 Clinical Research</name>
        <address>
          <city>Saint Petersburg</city>
          <country>Russian Federation</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Russian Federation</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 28, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Daratumumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05974969
  org study id: BCD-264-1
  nct id: NCT05974969
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical study is to establish the comparability of the pharmacokinetics and
        similarity of the safety, immunogenicity and pharmacodynamic profiles of BCD-264 and Darzalex
        following a single intravenous infusion in healthy subjects.
  In this clinical study, each subject will receive a single intravenous infusion of BCD-264 or
        Darzalex, depending on the group the subject will be randomized to. The drugs are
        administered at the study site at a dose of 8 mg/kg.
  
        The subjects will be followed up and blood samples collected for pharmacokinetics,
        pharmacodynamics, immunogenicity and safety studies up to and including 71 study days after
        the administration of IP.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Area under the serum concentration-time curve from time 0 to infinity (AUC0-∞)
  time frame: Up to Day 71
  measure: Area under the serum concentration-time curve from time 0 to the last measurable concentration (AUC0-t)
  time frame: Up to Day 71
  measure: Maximum observed drug concentration (Cmax)
  time frame: Up to Day 71
  measure: Time from administration to maximum observed concentration of the drug (Тmax)
  time frame: Up to Day 71
  measure: Elimination half-life (Т½)
  time frame: Up to Day 71
  measure: Elimination rate constant (Кel)
  time frame: Up to Day 71
  measure: Total clearance (Cl)
  time frame: Up to Day 71
  measure: Volume of distribution (Vd)
  time frame: Up to Day 71
  measure: Maximum effect (Emax)
  time frame: Up to Day 71
  description: Pharmacodynamics will be evaluated based on the absolute count and percentage of CD38+ cells in peripheral blood (T cells, B cells, NK cells, plasmablasts and plasma cells)
  measure: Time to maximum effect (TEmax)
  time frame: Up to Day 71
  description: Pharmacodynamics will be evaluated based on the absolute count and percentage of CD38+ cells in peripheral blood (T cells, B cells, NK cells, plasmablasts and plasma cells)
  measure: Incidence and characteristics of adverse events
  time frame: Up to Day 71
  measure: Proportion of subjects with BAbs/NAbs
  time frame: Up to Day 71
  measure: Time until the BAb/NAb development
  time frame: Up to Day 71
  arm group label: BCD-264
  arm group type: Experimental
  description: INN: daratumumab, single IV infusion at a dose of 8 mg/kg.
  arm group label: Darzalex
  arm group type: Active Comparator
  description: INN: daratumumab, single IV infusion at a dose of 8 mg/kg.
  intervention type: Drug
  intervention name: BCD-264
  description: a single intravenous infusion of BCD-264
  arm group label: BCD-264
  intervention type: Drug
  intervention name: Darzalex
  description: a single intravenous infusion of Darzalex
  arm group label: Darzalex
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  facility: 
  facility: 
  country: Russian Federation
  responsible party type: Sponsor
  mesh term: Daratumumab
  sharing ipd: No