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/NCT06010953</url>
    </required_header>
    <id_info>
      <org_study_id>SS-109-I02</org_study_id>
      <nct_id>NCT06010953</nct_id>
    </id_info>
    <brief_title>SS109 and NovoSeven ® PK / PD Profile, and Preliminary Efficacy and Safety of SS109 on Demand Treatment</brief_title>
    <official_title>An Open-label and Multicenter Phase Ib/II Clinical Trial to Evaluate the Safety, Immunogenicity, PK/PD Profile of SS109 and NovoSeven® Following a Single Dose, and the Preliminary Efficacy and Safety of SS109 During On-demand Treatment in Hemophilia Patients With Coagulation Factor VIII or IX Inhibitors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Jiangsu Gensciences lnc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Jiangsu Gensciences lnc.</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 an open-label, multicenter Phase 1Ib/2II clinical trial of SS109 in adult hemophilia&#xD;
        patients (≥ 18 years) with FVIII or FIX inhibitors to evaluate the PK/PD profile of SS109 and&#xD;
        NovoSeven® after a single dose in adult hemophilia patients with FVIII or FIX inhibitors, to&#xD;
        assess the preliminary efficacy and PK profile of SS109 during on-demand treatment, and to&#xD;
        observe the safety and immunogenicity of SS109 throughout the study.&#xD;
  &#xD;
        The trial consists of three periods: screening period, PK study period, and on-demand&#xD;
        treatment period.&#xD;
  &#xD;
        In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which&#xD;
        are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2&#xD;
        (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter&#xD;
        the PK study period as non-randomized. All screened eligible subjects will receive a single&#xD;
        dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by&#xD;
        PK/PD sample collection; then receive a single dose of the same dose of investigational drug&#xD;
        SS109, followed by PK/PD sample collection. Specific times for PK/PD sample collection are&#xD;
        listed in the schedule for biological sample collection.&#xD;
  &#xD;
        After completion of the PK study period, subjects will enter a 90-day on-demand treatment&#xD;
        period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group&#xD;
        3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand&#xD;
        with SS109 at the time of a new hemorrhage event and their efficacy is observed. The&#xD;
        investigator will judge the severity of subject's hemorrhage according to the type, location,&#xD;
        clinical symptoms and signs of the subject's hemorrhage. Appropriate hemostatic treatment&#xD;
        regimens and whether or not to perform the first SS109 on-demand treatment for the hemorrhage&#xD;
        event at home may be developed by the investigator based on the subject's on-demand treatment&#xD;
        group, according to the severity of hemorrhage and the recommended dosing frequency of SS109&#xD;
        (see Dosage/Regimen), and the dosing interval may be adjusted in conjunction with the&#xD;
        subject's response to treatment. If the subject's last hemostatic treatment is administered&#xD;
        within one week before the D96 visit point during the on-demand treatment period, the subject&#xD;
        is required to continue follow-up observation for one week after the last dose before&#xD;
        completing the end of study visit. PK/PD samples will be collected as appropriate during&#xD;
        on-demand treatment, as specified in the schedule for biological sample collection.Observe&#xD;
        subject safety throughout the study.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is an open-label, multicenter Phase 1Ib/2II clinical trial of SS109 in adult hemophilia&#xD;
        patients (≥ 18 years) with FVIII or FIX inhibitors to evaluate the PK/PD profile of SS109 and&#xD;
        NovoSeven® after a single dose in adult hemophilia patients with FVIII or FIX inhibitors, to&#xD;
        assess the preliminary efficacy and PK profile of SS109 during on-demand treatment, and to&#xD;
        observe the safety and immunogenicity of SS109 throughout the study.&#xD;
  &#xD;
        The trial consists of three periods: screening period, PK study period, and on-demand&#xD;
        treatment period.&#xD;
  &#xD;
        In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which&#xD;
        are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2&#xD;
        (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter&#xD;
        the PK study period as non-randomized. All screened eligible subjects will receive a single&#xD;
        dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by&#xD;
        PK/PD sample collection; then receive a single dose of the same dose of investigational drug&#xD;
        SS109, followed by PK/PD sample collection. Specific times for PK/PD sample collection are&#xD;
        listed in the schedule for biological sample collection.&#xD;
  &#xD;
        After completion of the PK study period, subjects will enter a 90-day on-demand treatment&#xD;
        period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group&#xD;
        3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand&#xD;
        with SS109 at the time of a new hemorrhage event and their efficacy is observed. The&#xD;
        investigator will judge the severity of subject's hemorrhage according to the type, location,&#xD;
        clinical symptoms and signs of the subject's hemorrhage. Appropriate hemostatic treatment&#xD;
        regimens and whether or not to perform the first SS109 on-demand treatment for the hemorrhage&#xD;
        event at home may be developed by the investigator based on the subject's on-demand treatment&#xD;
        group, according to the severity of hemorrhage and the recommended dosing frequency of SS109&#xD;
        (see Dosage/Regimen), and the dosing interval may be adjusted in conjunction with the&#xD;
        subject's response to treatment. If the subject's last hemostatic treatment is administered&#xD;
        within one week before the D96 visit point during the on-demand treatment period, the subject&#xD;
        is required to continue follow-up observation for one week after the last dose before&#xD;
        completing the end of study visit. PK/PD samples will be collected as appropriate during&#xD;
        on-demand treatment, as specified in the schedule for biological sample collection.&#xD;
  &#xD;
        Observe subject safety throughout the study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 24, 2023</start_date>
    <completion_date type="Anticipated">May 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">January 31, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</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>Cmax</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>According to the detected FVII activity of SS109 and NovoSeven®, the peak activity (Cmax)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Four-level rating scale to assess hemostasis</measure>
      <time_frame>Day 7 to Day 96</time_frame>
      <description>Hemostasis 12 h after on-demand treatment. For each new blood event, on-demand treatment should be conducted within 15min before each administration after the first dose&#xD;
  The hemostatic effect of pain and bleeding symptoms/signs observed and recorded after the last treatment was evaluated according to a four-level scoring scale.&#xD;
  If clinically effective (rated as &quot;excellent&quot; or &quot;good&quot;) is achieved, the evaluation is discontinued.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Tmax</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>According to the detected FVII activity of SS109 and NovoSeven®,time to peak concentration (Tmax),</description>
    </primary_outcome>
    <primary_outcome>
      <measure>AUC0-t</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-t) will be calculated</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Efficacy of hemostasis before each dose (except first dose) after treatment of all bleeding events</measure>
      <time_frame>Day 7 to Day 96</time_frame>
      <description>On-demand treatment Percentage rated &quot;good&quot; or &quot;very good&quot; before each dose after the first dose of on-demand treatmen</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to &quot;good&quot; or &quot;excellent&quot; evaluation after treatment for all hemorrhage events</measure>
      <time_frame>Day 7 to Day 96</time_frame>
      <description>Time to &quot;good&quot; or &quot;excellent&quot; evaluation after treatment for all hemorrhage events</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evaluate the incidence of AE/SAE/AESI</measure>
      <time_frame>Day 1 to Day 96</time_frame>
      <description>Safety Measures</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of positivity for FVII inhibitors</measure>
      <time_frame>Day 1 to Day 96</time_frame>
      <description>Immunogenicity Measure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>anti-drug antibodies (ADAs)</measure>
      <time_frame>Day 1 to Day 96</time_frame>
      <description>Immunogenicity Measures</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CHO host cell antibodies</measure>
      <time_frame>Day 1 to Day 96</time_frame>
      <description>Immunogenicity Measure</description>
    </secondary_outcome>
    <other_outcome>
      <measure>AUC0-inf</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>If data allows, the area under the concentration-time curve from time 0 to infinity (AUC0-inf)</description>
    </other_outcome>
    <other_outcome>
      <measure>(λz</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>clearance (CL), elimination rate constant (λz)</description>
    </other_outcome>
    <other_outcome>
      <measure>t1/2</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>elimination half-life</description>
    </other_outcome>
    <other_outcome>
      <measure>Vd</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>volume of distribution (Vd)</description>
    </other_outcome>
    <other_outcome>
      <measure>AUC_%Extrap</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>extrapolated percentage of area under the concentration-time curve (%) (AUC_%Extrap)</description>
    </other_outcome>
    <other_outcome>
      <measure>MRT</measure>
      <time_frame>Day 1 to Day 6</time_frame>
      <description>mean residence time</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Male</condition>
    <condition>Hemophilia A With Inhibitor</condition>
    <condition>Hemophilia B With Inhibitor</condition>
    <condition>Hemophilia</condition>
    <arm_group>
      <arm_group_label>PK period: Cohort 1 (90 μg/kg) and Cohort 2 (270 μg/kg)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2 (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter the PK study period as non-randomized. All screened eligible subjects will receive a single dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by PK/PD sample collection; then receive a single dose of the same dose of investigational drug SS109, followed by PK/PD sample collection.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>On-demand treatment period: Group 1：90 μg/kg Group 2：180 μg/kg Group 3：270 μg/kg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>After completion of the PK study period, subjects will enter a 90-day on-demand treatment period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group 3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand with SS109 at the time of a new hemorrhage event and their efficacy is observed.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>SS109</intervention_name>
      <description>on-demand treatment with SS109 at the time of a new hemorrhage event</description>
      <arm_group_label>On-demand treatment period: Group 1：90 μg/kg Group 2：180 μg/kg Group 3：270 μg/kg</arm_group_label>
      <arm_group_label>PK period: Cohort 1 (90 μg/kg) and Cohort 2 (270 μg/kg)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Aged 18 to 65 years at the time of informed consent, male;&#xD;
  &#xD;
            2. Patients with clinical diagnosis of hemophilia A or B (FVIII activity level ≤ 1% or&#xD;
               FIX activity level ≤ 2% in the previous or screening period) who meet one of the&#xD;
               following conditions:&#xD;
  &#xD;
               FVIII or FIX inhibitor level ≥ 5 Bu/mL at screening; FVIII or FIX inhibitor level &lt; 5&#xD;
               Bu/mL and ≥ 0.6 Bu/mL at screening, with a high response to coagulation factor VIII or&#xD;
               IX for injection (i.e., the patient has a previous history of positive FVIII/FIX&#xD;
               inhibitor and inhibitor levels are ≥ 5 Bu/mL after reinfusion of FVIII/FIX).&#xD;
  &#xD;
            3. No active bleeding symptoms prior to the first dose;&#xD;
  &#xD;
            4. Subjects or impartial witnesses fully understand and comply with the requirements of&#xD;
               the study protocol and are willing to complete the study as planned, and voluntarily&#xD;
               cooperate in providing biological samples for testing as required by the protocol;&#xD;
  &#xD;
            5. Be able to understand the procedures and methods of this clinical trial, and after&#xD;
               fully informed consent, the patient voluntarily participates and signs the informed&#xD;
               consent form by the patient himself or an impartial witness.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with a known history of hypersensitivity to the investigational product or&#xD;
               any of its components;&#xD;
  &#xD;
            2. Patients with previous hypersensitivity or anaphylaxis after FVII or IgG2 injection&#xD;
               therapy;&#xD;
  &#xD;
            3. Patients with positive FVII inhibitors or history of positive FVII inhibitors at&#xD;
               screening;&#xD;
  &#xD;
            4. Patients with severe anemia (hemoglobin &lt; 60 g/L);&#xD;
  &#xD;
            5. Patients with platelet count &lt; 100 × 109/L;&#xD;
  &#xD;
            6. Patients with abnormal liver and kidney function:&#xD;
  &#xD;
                 -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the&#xD;
                    upper limit of normal (ULN); or&#xD;
  &#xD;
                 -  Serum total bilirubin (TBIL) ≥ 1.5 times ULN; or&#xD;
  &#xD;
                 -  Serum creatinine (Cr) ≥ 1.5 times ULN or creatinine clearance &lt; 60 mL/min&#xD;
                    calculated according to the Cockcroft-Gault formula;&#xD;
  &#xD;
            7. Patients with one or more positive tests for hepatitis B virus surface antigen&#xD;
               (HBsAg), anti-hepatitis C virus (HCV) antibody, anti-human immunodeficiency virus&#xD;
               (HIV) antibody, and anti-treponema pallidum hemagglutination (TPHA)-specific antibody;&#xD;
  &#xD;
            8. With the exception of hemophilia A or B, any other haemorrhagic disorders or&#xD;
               significantly abnormal coagulation indicators (such as platelet disease, vitamin K&#xD;
               deficiency and hypofibrinogenaemia) caused by other diseases;&#xD;
  &#xD;
            9. Patients with fever, active infection and allergy (such as allergic rhinitis, allergic&#xD;
               asthma, allergic dermatitis) within 2 weeks before the first dose;&#xD;
  &#xD;
           10. Patients with severe cardiovascular and cerebrovascular diseases or thromboembolic&#xD;
               diseases occurred within 6 months before the first dose, such as cerebral arteritis,&#xD;
               moyamoya disease, cerebral stroke, viral myocarditis, endocarditis, endocardial&#xD;
               fibroelastosis, severe arrhythmia, myocardial infarction, unstable angina pectoris,&#xD;
               congestive heart failure (New York Heart Association Grade ≥ III), uncontrolled&#xD;
               hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100&#xD;
               mmHg) and uncontrolled diabetes;&#xD;
  &#xD;
           11. Patients receiving or planning to receive immune tolerance induction (ITI) treatment&#xD;
               during the trial;&#xD;
  &#xD;
           12. Receipt of any product containing FVII or FVIIa (plasma source or recombinant) within&#xD;
               24 hours before the first dose;&#xD;
  &#xD;
           13. Receipt of any product containing FVIII (plasma source or recombinant) within 72 hours&#xD;
               or 5 half-lives (whichever is longer) before the first dose or any product containing&#xD;
               FIX (plasma source or recombinant) within 96 hours or 5 half-lives (whichever is&#xD;
               longer) before the first dose;&#xD;
  &#xD;
           14. Patients who have used any anticoagulants, antifibrinolytic agents, and chemical&#xD;
               drugs, biological products or traditional Chinese medicines affecting platelet&#xD;
               function within 1 week before the first dose, including non-steroidal&#xD;
               anti-inflammatory drugs (NSAIDs) such as aspirin;&#xD;
  &#xD;
           15. Patients who have received emicizumab within 6 months before the first dose;&#xD;
  &#xD;
           16. Patients who have received immunomodulators (such as gamma globulin, interferon-alpha&#xD;
               and prednisone &gt; 10 mg/d [and &gt; 7 days] or similar drugs, except antiretroviral drugs)&#xD;
               within 2 weeks before the first dose;&#xD;
  &#xD;
           17. Patients who have received whole blood or plasma therapy within 2 weeks before the&#xD;
               first dose;&#xD;
  &#xD;
           18. Received vaccination within 4 weeks before the first dose or planned vaccination&#xD;
               during the PK study;&#xD;
  &#xD;
           19. Patients who underwent major surgical operations (e.g. orthopedic surgery, abdominal&#xD;
               surgery) within 1 month before the first dose, or plan to undergo surgery during the&#xD;
               study period;&#xD;
  &#xD;
           20. Patients who enrolled in other clinical trials within 1 month before the first dose;&#xD;
  &#xD;
           21. Patients with a history of drug abuse or alcoholism;&#xD;
  &#xD;
           22. Patients suffering from mental illness or obvious mental disorders, or incapacity or&#xD;
               cognitive inability due to other causes;&#xD;
  &#xD;
           23. Patients who have fertility plan or sperm donation plan during the whole trial period&#xD;
               and within 3 months after administration, or are unwilling to take effective physical&#xD;
               contraception measures (such as condom, diaphragm, intrauterine device);&#xD;
  &#xD;
           24. Patients who have clinically significant diseases or other reasons that, in the&#xD;
               opinion of the investigator, make participation in the clinical trial inappropriate&#xD;
               (e.g., patients who cannot benefit from the clinical trial);&#xD;
  &#xD;
           25. Subjects who, in the opinion of the investigator, have poor compliance that are not&#xD;
               evaluable for efficacy or are expected to have a low likelihood of completing the&#xD;
               intended course and follow-up.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Lili Xu</last_name>
      <phone>+8618518760326</phone>
      <email>lilixu@gensciences.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Anhui Provincial Hospital</name>
        <address>
          <city>Hefei</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Changcheng Zheng</last_name>
        <phone>+86 13956961162</phone>
        <email>zhengchch1123@163.com</email>
      </contact>
      <investigator>
        <last_name>Changcheng Zheng</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>The First Affiliated Hospital of Shandong First Medical University</name>
        <address>
          <city>Jinan</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Ning Huang</last_name>
        <phone>+8613006594815</phone>
        <email>huangninghbsct@sina.com</email>
      </contact>
      <investigator>
        <last_name>Ning Huang</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>The Second Affiliated Hospital of Kunming Medical University</name>
        <address>
          <city>Kunming</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Zeping Zhou</last_name>
        <phone>+8618788571605</phone>
        <email>zhouzeping@kmmu.edu.cn</email>
      </contact>
      <investigator>
        <last_name>Zeping Zhou</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Jiangxi Provincial People's Hospital</name>
        <address>
          <city>Nanchang</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Chenghao Jing</last_name>
        <phone>+8613699500207</phone>
        <email>jinch227@aliyun.com</email>
      </contact>
      <investigator>
        <last_name>Chenghao Jin</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Yangping Song</name>
        <address>
          <city>Shanxi</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yangping Ma</last_name>
        <phone>+8613834638353</phone>
      </contact>
      <investigator>
        <last_name>Yangping Ma</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Hematology Hospital, Chinese Academy of Medical Sciences</name>
        <address>
          <city>Tianjin</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Renchi Yang</last_name>
        <phone>+86 13512078851</phone>
        <email>rcyang@ihcams.ac.cn</email>
      </contact>
      <investigator>
        <last_name>Renchi Yang</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Xi'an Central Hospital</name>
        <address>
          <city>Xi'an</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yangping Song</last_name>
        <phone>+8613572973308</phone>
        <email>xjtusyp@163.com</email>
      </contact>
      <investigator>
        <last_name>Yangping Song</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Affiliated Hospital of Xuzhou Medical University</name>
        <address>
          <city>Xuzhou</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Zhenyu Li</last_name>
        <phone>+8615950688971</phone>
        <email>lizhenyumd@163.com</email>
      </contact>
      <investigator>
        <last_name>Zhenyu Li</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Henan Provincial Cancer Hospital</name>
        <address>
          <city>Zhengzhou</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Hu Zhou</last_name>
        <phone>+86 13939068863</phone>
        <email>papertigerhu@163.com</email>
      </contact>
      <investigator>
        <last_name>Hu Zhou</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 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>Hemophilia A</mesh_term>
      <mesh_term>Hemophilia B</mesh_term>
    </condition_browse>
    <!-- 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/NCT06010953
  org study id: SS-109-I02
  nct id: NCT06010953
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is an open-label, multicenter Phase 1Ib/2II clinical trial of SS109 in adult hemophilia
        patients (≥ 18 years) with FVIII or FIX inhibitors to evaluate the PK/PD profile of SS109 and
        NovoSeven® after a single dose in adult hemophilia patients with FVIII or FIX inhibitors, to
        assess the preliminary efficacy and PK profile of SS109 during on-demand treatment, and to
        observe the safety and immunogenicity of SS109 throughout the study.
  
        The trial consists of three periods: screening period, PK study period, and on-demand
        treatment period.
  
        In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which
        are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2
        (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter
        the PK study period as non-randomized. All screened eligible subjects will receive a single
        dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by
        PK/PD sample collection; then receive a single dose of the same dose of investigational drug
        SS109, followed by PK/PD sample collection. Specific times for PK/PD sample collection are
        listed in the schedule for biological sample collection.
  
        After completion of the PK study period, subjects will enter a 90-day on-demand treatment
        period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group
        3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand
        with SS109 at the time of a new hemorrhage event and their efficacy is observed. The
        investigator will judge the severity of subject's hemorrhage according to the type, location,
        clinical symptoms and signs of the subject's hemorrhage. Appropriate hemostatic treatment
        regimens and whether or not to perform the first SS109 on-demand treatment for the hemorrhage
        event at home may be developed by the investigator based on the subject's on-demand treatment
        group, according to the severity of hemorrhage and the recommended dosing frequency of SS109
        (see Dosage/Regimen), and the dosing interval may be adjusted in conjunction with the
        subject's response to treatment. If the subject's last hemostatic treatment is administered
        within one week before the D96 visit point during the on-demand treatment period, the subject
        is required to continue follow-up observation for one week after the last dose before
        completing the end of study visit. PK/PD samples will be collected as appropriate during
        on-demand treatment, as specified in the schedule for biological sample collection.Observe
        subject safety throughout the study.
  This is an open-label, multicenter Phase 1Ib/2II clinical trial of SS109 in adult hemophilia
        patients (≥ 18 years) with FVIII or FIX inhibitors to evaluate the PK/PD profile of SS109 and
        NovoSeven® after a single dose in adult hemophilia patients with FVIII or FIX inhibitors, to
        assess the preliminary efficacy and PK profile of SS109 during on-demand treatment, and to
        observe the safety and immunogenicity of SS109 throughout the study.
  
        The trial consists of three periods: screening period, PK study period, and on-demand
        treatment period.
  
        In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which
        are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2
        (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter
        the PK study period as non-randomized. All screened eligible subjects will receive a single
        dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by
        PK/PD sample collection; then receive a single dose of the same dose of investigational drug
        SS109, followed by PK/PD sample collection. Specific times for PK/PD sample collection are
        listed in the schedule for biological sample collection.
  
        After completion of the PK study period, subjects will enter a 90-day on-demand treatment
        period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group
        3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand
        with SS109 at the time of a new hemorrhage event and their efficacy is observed. The
        investigator will judge the severity of subject's hemorrhage according to the type, location,
        clinical symptoms and signs of the subject's hemorrhage. Appropriate hemostatic treatment
        regimens and whether or not to perform the first SS109 on-demand treatment for the hemorrhage
        event at home may be developed by the investigator based on the subject's on-demand treatment
        group, according to the severity of hemorrhage and the recommended dosing frequency of SS109
        (see Dosage/Regimen), and the dosing interval may be adjusted in conjunction with the
        subject's response to treatment. If the subject's last hemostatic treatment is administered
        within one week before the D96 visit point during the on-demand treatment period, the subject
        is required to continue follow-up observation for one week after the last dose before
        completing the end of study visit. PK/PD samples will be collected as appropriate during
        on-demand treatment, as specified in the schedule for biological sample collection.
  
        Observe subject safety throughout the study.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Cmax
  time frame: Day 1 to Day 6
  description: According to the detected FVII activity of SS109 and NovoSeven®, the peak activity (Cmax)
  measure: Four-level rating scale to assess hemostasis
  time frame: Day 7 to Day 96
  description: Hemostasis 12 h after on-demand treatment. For each new blood event, on-demand treatment should be conducted within 15min before each administration after the first dose
  The hemostatic effect of pain and bleeding symptoms/signs observed and recorded after the last treatment was evaluated according to a four-level scoring scale.
  If clinically effective (rated as "excellent" or "good") is achieved, the evaluation is discontinued.
  measure: Tmax
  time frame: Day 1 to Day 6
  description: According to the detected FVII activity of SS109 and NovoSeven®,time to peak concentration (Tmax),
  measure: AUC0-t
  time frame: Day 1 to Day 6
  description: area under the concentration-time curve from time 0 to the last quantifiable time point (AUC0-t) will be calculated
  measure: Efficacy of hemostasis before each dose (except first dose) after treatment of all bleeding events
  time frame: Day 7 to Day 96
  description: On-demand treatment Percentage rated "good" or "very good" before each dose after the first dose of on-demand treatmen
  measure: Time to "good" or "excellent" evaluation after treatment for all hemorrhage events
  time frame: Day 7 to Day 96
  description: Time to "good" or "excellent" evaluation after treatment for all hemorrhage events
  measure: Evaluate the incidence of AE/SAE/AESI
  time frame: Day 1 to Day 96
  description: Safety Measures
  measure: Incidence of positivity for FVII inhibitors
  time frame: Day 1 to Day 96
  description: Immunogenicity Measure
  measure: anti-drug antibodies (ADAs)
  time frame: Day 1 to Day 96
  description: Immunogenicity Measures
  measure: CHO host cell antibodies
  time frame: Day 1 to Day 96
  description: Immunogenicity Measure
  measure: AUC0-inf
  time frame: Day 1 to Day 6
  description: If data allows, the area under the concentration-time curve from time 0 to infinity (AUC0-inf)
  measure: (λz
  time frame: Day 1 to Day 6
  description: clearance (CL), elimination rate constant (λz)
  measure: t1/2
  time frame: Day 1 to Day 6
  description: elimination half-life
  measure: Vd
  time frame: Day 1 to Day 6
  description: volume of distribution (Vd)
  measure: AUC_%Extrap
  time frame: Day 1 to Day 6
  description: extrapolated percentage of area under the concentration-time curve (%) (AUC_%Extrap)
  measure: MRT
  time frame: Day 1 to Day 6
  description: mean residence time
  arm group label: PK period: Cohort 1 (90 μg/kg) and Cohort 2 (270 μg/kg)
  arm group type: Experimental
  description: In the PK study period, subjects are divided into 2 cohorts (90 μg/kg and 270 μg/kg), which are sequentially conducted. Cohort 1 (90 μg/kg) enrollment is performed firstly, and Cohort 2 (270 μg/kg) enrollment is performed after Cohort 1 enrollment is completed. Subjects enter the PK study period as non-randomized. All screened eligible subjects will receive a single dose of comparator NovoSeven® in the absence of significant active hemorrhage, followed by PK/PD sample collection; then receive a single dose of the same dose of investigational drug SS109, followed by PK/PD sample collection.
  arm group label: On-demand treatment period: Group 1：90 μg/kg Group 2：180 μg/kg Group 3：270 μg/kg
  arm group type: Experimental
  description: After completion of the PK study period, subjects will enter a 90-day on-demand treatment period and will be randomized into 3 groups (Group 1: 90 µg/kg, Group 2: 180 µg/kg, and Group 3: 270 µg/kg) at a ratio of 1:1:1. During on-demand treatment, subjects are treated on-demand with SS109 at the time of a new hemorrhage event and their efficacy is observed.
  intervention type: Drug
  intervention name: SS109
  description: on-demand treatment with SS109 at the time of a new hemorrhage event
  arm group label: On-demand treatment period: Group 1：90 μg/kg Group 2：180 μg/kg Group 3：270 μg/kg
  arm group label: PK period: Cohort 1 (90 μg/kg) and Cohort 2 (270 μg/kg)
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Lili Xu
  phone: +8618518760326
  email: lilixu@gensciences.cn
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  country: China
  responsible party type: Sponsor
  mesh term: Hemophilia A
  mesh term: Hemophilia B