<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/NCT03815318</url>
  </required_header>
  <id_info>
    <org_study_id>SCT800-A 302</org_study_id>
    <nct_id>NCT03815318</nct_id>
  </id_info>
  <brief_title>Evaluation of SCT800 in Prophylaxis Therapy on Previous Treated Patients With Severe Hemophilia A</brief_title>
  <official_title>A Multicenter, Open, Single Arm Evaluation of the Efficacy, Safety and Pharmacokinetics of Recombinant Human Coagulation FVIII (SCT800) in Prophylaxis Therapy on Patients With Severe Hemophilia A Who Had Previously Treated With FVIII.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sinocelltech Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Q2 Solutions</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sinocelltech 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 study is a multi-center, open-label, single-arm trial to evaluate the efficacy,safety&#xD;
      and pharmacokinetics of SCT800 in regular prophylaxis and perioperative treatment in patients&#xD;
      (≥12 years old) with severe hemophilia A who have been previously treated with coagulation&#xD;
      factor VIII(FVIII:C) . This study includes two phases: the screening period and prophylaxis&#xD;
      period.Prophylaxis with 25 - 50 IU/kg of SCT800 shall be administered once every other day or&#xD;
      three times per week starting from V1 and prophylaxis with SCT800 shall continue for 24&#xD;
      consecutive weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After subjects pass screening, prophylaxis with 25 - 50 IU/kg of SCT800 shall be administered&#xD;
      once every other day or three times per week for 6 months. Subjects shall receive FVIII&#xD;
      intravenous injection treatment at the study site or at home. During the study prophylaxis&#xD;
      treatment period, subjects should return for visit every four weeks, namely for Visit (V) 2&#xD;
      (4 weeks ± 4 days), Visit 3 (8 weeks ± 4 days), Visit 4 (12 weeks ± 4 days), Visit 5 (16&#xD;
      weeks ± 7 days), Visit 6 (20 weeks ± 7 days), Visit 7 (24 weeks ± 7 days) and&#xD;
      end-of-treatment (EOT) visit (+ 14 days). Of which, blood collection shall be carried out&#xD;
      during the screening period and in V1, V2, V4, V7 and the EOT visit for FVIII inhibitor&#xD;
      assay; blood collection shall be carried out before and after the completion of SCT800&#xD;
      infusion in V1, V4 and V7 for incremental in-vivo recovery (IVR) assay.&#xD;
&#xD;
      FVIII:C activity shall be monitored before injection and 15minutes(min), 30min, 1h, 3h, 6h,&#xD;
      9h, 12h, 24hours(h), 28h, 32h and 48h after injection at V1 and V7. Then pharmacokinetics&#xD;
      parameters (incremental in-vivo recovery, t1/2 etc.) of SCT800 shall be calculated and&#xD;
      evaluated.&#xD;
&#xD;
      5 subjects may receive elective surgical treatment within the prophylaxis treatment period&#xD;
      (after the first drug administration in day 0).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Actual">January 16, 2020</completion_date>
  <primary_completion_date type="Actual">January 16, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Annualized Bleeding Rate</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>Annualized Bleeding Rate（ABR） can be calculated using the following formula: Number of bleeding events in efficacy evaluation period/(number of days in treatment period/365.25)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized joint bleeding rate</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>Annualized joint bleeding rate（AJBR） can be calculated using the following formula: Number of joint bleeding events during efficacy evaluation period/(number of days in treatment period/365.25).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVIII incremental in-vivo recovery</measure>
    <time_frame>Predose within 30 min，15 min±2 min、1 hour±5 min.</time_frame>
    <description>Incremental recovery is determined as the peak factor level recorded in the first hour after infusion and is reported as [IU/ml]/[IU/kg]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bleeding event treatment efficacy</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>The investigator shall evaluate the hemostatic effect after the treatment of every bleeding event of subjects based on a four-point scale(excellent, good, moderate, not relieved).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination Half Life</measure>
    <time_frame>Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.</time_frame>
    <description>t1/2; One-stage aPTT Clotting Assay and Chromogenic Assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance</measure>
    <time_frame>Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.</time_frame>
    <description>CL; One-stage aPTT Clotting Assay and Chromogenic Assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve to the Last Measurable Timepoint</measure>
    <time_frame>Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.</time_frame>
    <description>AUClast;One-stage aPTT Clotting Assay and Chromogenic Assay</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of FVIII inhibitors</measure>
    <time_frame>up tp 24 weeks</time_frame>
    <description>The Nijmegen-Bethesda assay shall be used to monitor the production of FVIII inhibitors during the trial.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Hemophilia A</condition>
  <arm_group>
    <arm_group_label>Recombinant Human Coagulation FVIII</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participant receivedSCT800 for prophylaxis with 25 - 50 IU/kg injection once every other day or three times per week for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Recombinant Human Coagulation FVIII</intervention_name>
    <description>Participant received SCT800 for prophylaxis with 25 - 50 IU/kg injection once every other day or three times per week for 6 months.</description>
    <arm_group_label>Recombinant Human Coagulation FVIII</arm_group_label>
    <other_name>SCT800</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged ≥12 years old and ≤65 years old;&#xD;
&#xD;
          -  Male patients who are clinically diagnosed with severe (laboratory tested FVIII:C &lt;1%)&#xD;
             hemophilia A, including historical FVIII:C &lt;1%;&#xD;
&#xD;
          -  Previously received FVIII treatment (prophylactic or bleeding treatment), have the&#xD;
             relevant records and are verified to have accumulated exposures days( EDs) ≥150 days;&#xD;
&#xD;
          -  The bleeding treatment records of at least 3 months before screening can be obtained;&#xD;
&#xD;
          -  Negative FVIII inhibitor assay results (laboratory tested Nijmegen-Bethesda assay&#xD;
             result &lt;0.6 BU(Bethesda unit)/mL);&#xD;
&#xD;
          -  The prothrombin time is normal or international normalized ratio (INR) ≤1.5; 7.&#xD;
             Platelet count ≥100 × 109/L;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy to recombinant coagulation factor VIII concentrate or any excipient;&#xD;
             known allergy to bovine, rodent or hamster bovine;&#xD;
&#xD;
          -  Has a history or family history of blood coagulation factor VIII inhibitor;&#xD;
&#xD;
          -  Clinical liver function test (glutamic-pyruvic transaminase, glutamic-pyruvic&#xD;
             transaminase) ≥ three times the upper limit of normal (ULN) or clinical kidney&#xD;
             function test (blood urea nitrogen, creatinine) ≥ three times the ULN;&#xD;
&#xD;
          -  Patients clinically diagnosed with active Hepatitis B or Hepatitis C;&#xD;
&#xD;
          -  Patients with other coagulation dysfunction diseases in addition to hemophilia A;&#xD;
&#xD;
          -  Patients with severe heart disease, including myocardial infarction and cardiac&#xD;
             dysfunction of class III or above;&#xD;
&#xD;
          -  Patients who previously experienced intracranial bleeding;&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Hemophilia A is a kind of sex chromosome recessive genetic disease and ofter occurs in male.</gender_description>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Renchi Yang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College</name>
      <address>
        <city>Tianjin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 20, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>February 4, 2020</last_update_submitted>
  <last_update_submitted_qc>February 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2020</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>
  </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/NCT03815318
org study id: SCT800-A 302
nct id: NCT03815318
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a multi-center, open-label, single-arm trial to evaluate the efficacy,safety
      and pharmacokinetics of SCT800 in regular prophylaxis and perioperative treatment in patients
      (≥12 years old) with severe hemophilia A who have been previously treated with coagulation
      factor VIII(FVIII:C) . This study includes two phases: the screening period and prophylaxis
      period.Prophylaxis with 25 - 50 IU/kg of SCT800 shall be administered once every other day or
      three times per week starting from V1 and prophylaxis with SCT800 shall continue for 24
      consecutive weeks.
After subjects pass screening, prophylaxis with 25 - 50 IU/kg of SCT800 shall be administered
      once every other day or three times per week for 6 months. Subjects shall receive FVIII
      intravenous injection treatment at the study site or at home. During the study prophylaxis
      treatment period, subjects should return for visit every four weeks, namely for Visit (V) 2
      (4 weeks ± 4 days), Visit 3 (8 weeks ± 4 days), Visit 4 (12 weeks ± 4 days), Visit 5 (16
      weeks ± 7 days), Visit 6 (20 weeks ± 7 days), Visit 7 (24 weeks ± 7 days) and
      end-of-treatment (EOT) visit (+ 14 days). Of which, blood collection shall be carried out
      during the screening period and in V1, V2, V4, V7 and the EOT visit for FVIII inhibitor
      assay; blood collection shall be carried out before and after the completion of SCT800
      infusion in V1, V4 and V7 for incremental in-vivo recovery (IVR) assay.

      FVIII:C activity shall be monitored before injection and 15minutes(min), 30min, 1h, 3h, 6h,
      9h, 12h, 24hours(h), 28h, 32h and 48h after injection at V1 and V7. Then pharmacokinetics
      parameters (incremental in-vivo recovery, t1/2 etc.) of SCT800 shall be calculated and
      evaluated.

      5 subjects may receive elective surgical treatment within the prophylaxis treatment period
      (after the first drug administration in day 0).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Annualized Bleeding Rate
time frame: up to 24 weeks
description: Annualized Bleeding Rate（ABR） can be calculated using the following formula: Number of bleeding events in efficacy evaluation period/(number of days in treatment period/365.25)
measure: Annualized joint bleeding rate
time frame: up to 24 weeks
description: Annualized joint bleeding rate（AJBR） can be calculated using the following formula: Number of joint bleeding events during efficacy evaluation period/(number of days in treatment period/365.25).
measure: FVIII incremental in-vivo recovery
time frame: Predose within 30 min，15 min±2 min、1 hour±5 min.
description: Incremental recovery is determined as the peak factor level recorded in the first hour after infusion and is reported as [IU/ml]/[IU/kg]
measure: Bleeding event treatment efficacy
time frame: up to 24 weeks
description: The investigator shall evaluate the hemostatic effect after the treatment of every bleeding event of subjects based on a four-point scale(excellent, good, moderate, not relieved).
measure: Elimination Half Life
time frame: Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.
description: t1/2; One-stage aPTT Clotting Assay and Chromogenic Assay
measure: Clearance
time frame: Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.
description: CL; One-stage aPTT Clotting Assay and Chromogenic Assay
measure: Area Under the Curve to the Last Measurable Timepoint
time frame: Predose within 30 min，15 min±2 min、30 min±2 min，1 hour±5 min，3 hours±5 min，6 hours±5 min，9 hours±10 min，12hours h±10 min，24 hours±10 min，28 hours±10 min，32 hours±10 min and 48 hours±10 min post-dose.
description: AUClast;One-stage aPTT Clotting Assay and Chromogenic Assay
measure: Incidence of FVIII inhibitors
time frame: up tp 24 weeks
description: The Nijmegen-Bethesda assay shall be used to monitor the production of FVIII inhibitors during the trial.
arm group label: Recombinant Human Coagulation FVIII
arm group type: Experimental
description: Participant receivedSCT800 for prophylaxis with 25 - 50 IU/kg injection once every other day or three times per week for 6 months.
intervention type: Drug
intervention name: Recombinant Human Coagulation FVIII
description: Participant received SCT800 for prophylaxis with 25 - 50 IU/kg injection once every other day or three times per week for 6 months.
arm group label: Recombinant Human Coagulation FVIII
other name: SCT800
criteria: 
gender: Male
gender based: Yes
gender description: Hemophilia A is a kind of sex chromosome recessive genetic disease and ofter occurs in male.
minimum age: 12 Years
maximum age: 65 Years
healthy volunteers: No
last name: Renchi Yang
role: Principal Investigator
affiliation: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
facility: 
country: China
responsible party type: Sponsor
mesh term: Hemophilia A