<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/NCT03254810</url>
  </required_header>
  <id_info>
    <org_study_id>SYN060-001</org_study_id>
    <nct_id>NCT03254810</nct_id>
  </id_info>
  <brief_title>Comparison of the Safety and PK of SYN060 to Humira® in Healthy Adult Subjects</brief_title>
  <official_title>A Phase 1 Randomized Blinded Single Dose Comparison of the Safety and Pharmacokinetics of SYN060 Compared to Adalimumab (Humira®) From North American and European Sources in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Synermore Biologics Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Synermore Biologics 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 single site, parallel randomized, double blinded comparison of the safety,&#xD;
      pharmacokinetics, and immunogenicity of a single 0.57 mg/kg dose of SYN060 to a single 0.57&#xD;
      mg/kg dose of adalimumab (Humira®) reference product from North American and European&#xD;
      sources. The study is open to healthy individuals on no medications that might confound the&#xD;
      results of this safety study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single site, parallel randomized, double blinded comparison of the safety,&#xD;
      pharmacokinetics, and immunogenicity of a single 0.57 mg/kg dose of SYN060 to a single 0.57&#xD;
      mg/kg dose of adalimumab (Humira®) reference product from North American and European&#xD;
      sources. The study is open to healthy individuals on no medications that might confound the&#xD;
      results of this safety study.&#xD;
&#xD;
      A total of 90 subjects will be randomized in a 1:1:1 ratio to from a centrally generated&#xD;
      randomization schedule to SYN060 or adalimumab of American or European sources resulting in&#xD;
      30 subjects in each group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Actual">July 17, 2018</completion_date>
  <primary_completion_date type="Actual">July 17, 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-last (area under the concentration-time curve from time zero to the last non-zero concentration) and AUC0-inf (area under the concentration-time curve from time zero to infinity)</measure>
    <time_frame>85 days</time_frame>
    <description>AUC0-last and AUC0-inf will be estimated using non-compartmental analysis fpr SYN060 to adalimumab (Humira®) from North American and European sources.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum observed concentration)</measure>
    <time_frame>85 days</time_frame>
    <description>Cmax will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Residual area (%AUCextrap) [percent extrapolated area under the curve to infinity calculated as 100*(1- AUC0-last / AUC0-inf)]</measure>
    <time_frame>85 days</time_frame>
    <description>Residual area (%AUCextrap) will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax (time of observed Cmax)</measure>
    <time_frame>85 days</time_frame>
    <description>Tmax will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <primary_outcome>
    <measure>t½ (elimination half-life)</measure>
    <time_frame>85 days</time_frame>
    <description>t½ will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <primary_outcome>
    <measure>λz (elimination rate constant)</measure>
    <time_frame>85 days</time_frame>
    <description>λz will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CL/F (apparent body clearance, calculated as Dose/AUC0-inf)</measure>
    <time_frame>85 days</time_frame>
    <description>CL/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vz/F [apparent volume of distribution, calculated as Dose/ (λz x AUC0-inf)]</measure>
    <time_frame>85 days</time_frame>
    <description>Vz/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse event incidence of SYN060 compared to adalimumab (Humira®) from North American and European sources</measure>
    <time_frame>85 days</time_frame>
    <description>Safety monitoring will include vital signs (blood pressure, temperature, pulse, oximetry and respiration rates), physical examination, electrocardiogram (ECG) and clinical laboratory tests (serum chemistry, hematology, troponins, creatinine phosphokinase [CPK], human anti-SYN060 antibodies, human anti-adalimumab antibodies and urinalysis). Adverse events will be recorded throughout the study and will be coded using the most current version of MedDRA (Medical Dictionary for Regulatory Activities) at the time of study commencement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-SYN060 antibodies</measure>
    <time_frame>85 days</time_frame>
    <description>The development of anti-SYN060 antibodieswill be determined on Study Days 0, and 7 through 85, or the last blood specimen available for subjects who leave the study prior to Day 85. The development of anti-SYN060 antibodies will be analyzed as a continuous measure across categorical groups and compared to anti-adalimumab antibodies with descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-adalimumab antibodies</measure>
    <time_frame>85 days</time_frame>
    <description>The development of anti-adalimumab antibodies will be determined on Study Days 0, and 7 through 85, or the last blood specimen available for subjects who leave the study prior to Day 85. The development of anti-adalimumab antibodies will be analyzed as a continuous measure across categorical groups and compared to anti-SYN060 antibodies with descriptive statistics.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">94</enrollment>
  <condition>Arthritis, Rheumatoid</condition>
  <arm_group>
    <arm_group_label>SYN060</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>a single 0.57 mg/kg dose of SYN060</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adalimumab North American source</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a single 0.57 mg/kg dose of adalimumab from North American source</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adalimumab European source</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a single 0.57 mg/kg dose of adalimumab from European source</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SYN060</intervention_name>
    <description>a single subcutaneous 0.57 mg/kg dose of SYN060</description>
    <arm_group_label>SYN060</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab North American source</intervention_name>
    <description>a single subcutaneous 0.57 mg/kg dose of adalimumab (Humira®) reference product from North American source</description>
    <arm_group_label>Adalimumab North American source</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab European source</intervention_name>
    <description>a single subcutaneous 0.57 mg/kg dose of adalimumab (Humira®) reference product from European source</description>
    <arm_group_label>Adalimumab European source</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects between 18 and 50 years of age, inclusive&#xD;
&#xD;
          2. Body mass index between 18 and 30 kg/m², inclusive&#xD;
&#xD;
          3. Female subjects physically capable of pregnancy (i.e., not sterilized and still&#xD;
             menstruating or within 1 year of the last menses if menopausal) must:&#xD;
&#xD;
               1. Agree to avoid pregnancy from the Study Day screening visit through six months&#xD;
                  after receipt of Study Drug.&#xD;
&#xD;
               2. If in a sexual relationship with a man, use an acceptable method of avoiding&#xD;
                  pregnancy during this period, still menstruating or within 1 year of the last&#xD;
                  menses if menopausal) in sexual relationships with men must use an acceptable&#xD;
                  method of avoiding pregnancy during this period. Acceptable methods of avoiding&#xD;
                  pregnancy include a sterile sexual partner, sexual abstinence (not engaging in&#xD;
                  sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch,&#xD;
                  or implant), vaginal ring or intrauterine device (IUD).&#xD;
&#xD;
          4. Women of childbearing potential must have a negative serum pregnancy test within 24&#xD;
             hours preceding receipt of the dose.&#xD;
&#xD;
          5. Can understand and sign the informed consent document, can communicate with the&#xD;
             investigator and provide updated contact information as needed for the duration of the&#xD;
             study, has no current plans to move from the study area for the duration of the study,&#xD;
             and can understand and comply with the requirements of the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute illness on Study Day 1&#xD;
&#xD;
          2. Oral temperature ≥37.5°C on Study Day 1&#xD;
&#xD;
          3. Inability to discontinue daily medications other than oral contraceptives or other&#xD;
             hormonal therapy.&#xD;
&#xD;
          4. Receipt of an immunoglobulin or blood product within 90 days prior to Study Day 1&#xD;
&#xD;
          5. Any receipt of adalimumab, or other licensed monoclonal antibody&#xD;
&#xD;
          6. Any receipt of another investigational product within 4 weeks or 4 half-lives&#xD;
             whichever is longer prior to Study Day 1&#xD;
&#xD;
          7. Abnormal laboratory values per local laboratory parameters from blood collected at&#xD;
             screening prior to Study Day 1 randomization as follows:&#xD;
&#xD;
               -  Severe anemia, defined as haemoglobin &lt;100 g/L or hematocrit &lt;0.3 L/L&#xD;
&#xD;
               -  absolute neutrophil count, below lower limit of normal (LLN)&#xD;
&#xD;
               -  white blood cell count above upper limit of normal (ULN) or below LLN (i.e., must&#xD;
                  be within normal limits)&#xD;
&#xD;
               -  ALT, AST, alkaline phosphatase (ALP) above ULN with exception that a one of the&#xD;
                  three values may be permitted up to 10% above ULN.&#xD;
&#xD;
               -  Creatinine above upper limit of normal ,&#xD;
&#xD;
               -  INR, or activated partial thromboplastin time (APTT) above ULN&#xD;
&#xD;
          8. Abnormal screening urinalysis result that is, per the investigator, clinically&#xD;
             significant, or a screening urine dipstick result of ≥2+ protein&#xD;
&#xD;
          9. Positive screening urine test for illicit drugs (amphetamines, methamphetamines,&#xD;
             barbiturates, benzodiazepine, cocaine, opiates, PCP, MDMA, methadone)&#xD;
&#xD;
         10. History of systemic allergic reactions, to more than one medication.&#xD;
&#xD;
         11. History or evidence of malignancy.&#xD;
&#xD;
         12. Receipt of immunosuppressive medications other than inhaled or topical&#xD;
             immunosuppressant drugs such as corticosteroids within 45 days prior to Study Day 1&#xD;
&#xD;
         13. Hepatitis B surface antigen positive, HIV positive, hepatitis C antibody positive&#xD;
&#xD;
         14. Uncontrolled Type 2 Diabetes or Type I diabetes&#xD;
&#xD;
         15. History systemic fungal infection.&#xD;
&#xD;
         16. Shared a residence within the last year with an individual on anti-tuberculosis&#xD;
             treatment or with culture or smear positive tuberculosis&#xD;
&#xD;
         17. Previous medical history that may compromise the safety of the subject in the study,&#xD;
             including but not limited to: severe impairment of pulmonary function or other&#xD;
             pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected&#xD;
             progressive neurological disease or poorly controlled epilepsy&#xD;
&#xD;
         18. History or evidence on physical examination of any systemic disease or any acute or&#xD;
             chronic illness that, in the opinion of the investigator, may interfere with the&#xD;
             evaluation of the safety of the Study Drug&#xD;
&#xD;
         19. History or evidence of tuberculosis infection&#xD;
&#xD;
         20. Positive Quantiferon test&#xD;
&#xD;
         21. Chest X ray with evidence of malignancy or chronic infection (such as tuberculosis or&#xD;
             other)&#xD;
&#xD;
         22. Any current medical, psychiatric, occupational, or substance abuse problem such as&#xD;
             alcoholism that, in the opinion of the investigator, will make it unlikely that the&#xD;
             subject will comply with the protocol.&#xD;
&#xD;
         23. Elective surgery that would interfere with participation.&#xD;
&#xD;
         24. Live virus vaccination within 60 days and during the study.&#xD;
&#xD;
         25. Blood donation less than 30 days prior to Study Day 1.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Niquita Tugiono, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nucleus Network, Center for Clinical Studies Study Site</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nucleus Network</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>November 16, 2018</last_update_submitted>
  <last_update_submitted_qc>November 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 19, 2018</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>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adalimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03254810
org study id: SYN060-001
nct id: NCT03254810
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a single site, parallel randomized, double blinded comparison of the safety,
      pharmacokinetics, and immunogenicity of a single 0.57 mg/kg dose of SYN060 to a single 0.57
      mg/kg dose of adalimumab (Humira®) reference product from North American and European
      sources. The study is open to healthy individuals on no medications that might confound the
      results of this safety study.
This is a single site, parallel randomized, double blinded comparison of the safety,
      pharmacokinetics, and immunogenicity of a single 0.57 mg/kg dose of SYN060 to a single 0.57
      mg/kg dose of adalimumab (Humira®) reference product from North American and European
      sources. The study is open to healthy individuals on no medications that might confound the
      results of this safety study.

      A total of 90 subjects will be randomized in a 1:1:1 ratio to from a centrally generated
      randomization schedule to SYN060 or adalimumab of American or European sources resulting in
      30 subjects in each group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: AUC0-last (area under the concentration-time curve from time zero to the last non-zero concentration) and AUC0-inf (area under the concentration-time curve from time zero to infinity)
time frame: 85 days
description: AUC0-last and AUC0-inf will be estimated using non-compartmental analysis fpr SYN060 to adalimumab (Humira®) from North American and European sources.
measure: Cmax (maximum observed concentration)
time frame: 85 days
description: Cmax will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: Residual area (%AUCextrap) [percent extrapolated area under the curve to infinity calculated as 100*(1- AUC0-last / AUC0-inf)]
time frame: 85 days
description: Residual area (%AUCextrap) will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: Tmax (time of observed Cmax)
time frame: 85 days
description: Tmax will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: t½ (elimination half-life)
time frame: 85 days
description: t½ will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: λz (elimination rate constant)
time frame: 85 days
description: λz will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: CL/F (apparent body clearance, calculated as Dose/AUC0-inf)
time frame: 85 days
description: CL/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: Vz/F [apparent volume of distribution, calculated as Dose/ (λz x AUC0-inf)]
time frame: 85 days
description: Vz/F will be estimated using non-compartmental analysis for SYN060 and adalimumab (Humira®) from North American and European sources
measure: Adverse event incidence of SYN060 compared to adalimumab (Humira®) from North American and European sources
time frame: 85 days
description: Safety monitoring will include vital signs (blood pressure, temperature, pulse, oximetry and respiration rates), physical examination, electrocardiogram (ECG) and clinical laboratory tests (serum chemistry, hematology, troponins, creatinine phosphokinase [CPK], human anti-SYN060 antibodies, human anti-adalimumab antibodies and urinalysis). Adverse events will be recorded throughout the study and will be coded using the most current version of MedDRA (Medical Dictionary for Regulatory Activities) at the time of study commencement.
measure: anti-SYN060 antibodies
time frame: 85 days
description: The development of anti-SYN060 antibodieswill be determined on Study Days 0, and 7 through 85, or the last blood specimen available for subjects who leave the study prior to Day 85. The development of anti-SYN060 antibodies will be analyzed as a continuous measure across categorical groups and compared to anti-adalimumab antibodies with descriptive statistics.
measure: anti-adalimumab antibodies
time frame: 85 days
description: The development of anti-adalimumab antibodies will be determined on Study Days 0, and 7 through 85, or the last blood specimen available for subjects who leave the study prior to Day 85. The development of anti-adalimumab antibodies will be analyzed as a continuous measure across categorical groups and compared to anti-SYN060 antibodies with descriptive statistics.
arm group label: SYN060
arm group type: Experimental
description: a single 0.57 mg/kg dose of SYN060
arm group label: Adalimumab North American source
arm group type: Active Comparator
description: a single 0.57 mg/kg dose of adalimumab from North American source
arm group label: Adalimumab European source
arm group type: Active Comparator
description: a single 0.57 mg/kg dose of adalimumab from European source
intervention type: Biological
intervention name: SYN060
description: a single subcutaneous 0.57 mg/kg dose of SYN060
arm group label: SYN060
intervention type: Biological
intervention name: Adalimumab North American source
description: a single subcutaneous 0.57 mg/kg dose of adalimumab (Humira®) reference product from North American source
arm group label: Adalimumab North American source
intervention type: Biological
intervention name: Adalimumab European source
description: a single subcutaneous 0.57 mg/kg dose of adalimumab (Humira®) reference product from European source
arm group label: Adalimumab European source
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Niquita Tugiono, MD
role: Principal Investigator
affiliation: Nucleus Network, Center for Clinical Studies Study Site
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Arthritis, Rheumatoid
mesh term: Adalimumab
sharing ipd: No