<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/NCT04465890</url>
  </required_header>
  <id_info>
    <org_study_id>ASC-ASC22-II-CTP-01</org_study_id>
    <nct_id>NCT04465890</nct_id>
  </id_info>
  <brief_title>A Phase II Study of Subcutaneously Injected PD-L1 Antibody ASC22 in Chronic Hepatitis B Patients</brief_title>
  <official_title>Phase IIa Single Dose and Phase IIb Mutiple Dose Clinical Studies to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Subcutaneously Injected PD-L1 Antibody ASC22 in Patients With Chronic Hepatitis B</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ascletis Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Peking University First Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Clinical Service Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ascletis Pharmaceuticals Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to evaluate the safety and efficacy of ASC22 in the treatment&#xD;
      of chronic hepatitis B after single and multiple drug administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study consists of two parts: the ASC22 single-dose IIa study and the ASC22 multi-dose IIb&#xD;
      study. The IIa study consists of 3 cohorts of 0.3mg/kg, 1.0mg/kg and 2.5mg/kg, and the IIb&#xD;
      study consists of 2 cohorts of 1.0mg/kg and 2.5mg/kg. The objective is to evaluate the&#xD;
      safety, tolerance and efficacy of ASC22 in patients with chronic hepatitis B (CHB), and to&#xD;
      provide a guidance for the determination of dosage regimen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 17, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the decreased HBsAg levels at 12 or 24 weeks of treatment or at 4, 12, or 24 weeks of follow-up visits compared with baseline.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluate the number of patients with ≥0.5log reduction in HBsAg log10IU/ mL at 12 or 24 weeks of treatment, or at 4, 12, or 24 weeks of follow-up visits compared with baseline.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the decline value of HBsAg level.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the propotion's change of HBsAg &lt; 0.05IU/ml in each cohort.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the changes of peripheral blood lymphocyte subsets in each cohort.</measure>
    <time_frame>48 weeks</time_frame>
    <description>Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Anticipated">208</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <arm_group>
    <arm_group_label>cohort1: Single dose ASC22 injection 0.3mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort2:Single dose ASC22 injection 1.0mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort3:Single dose ASC22 injection 2.5mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort4: Multiple dose ASC22 injection 1.0mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort5: Multiple dose ASC22 injection 2.5mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort4: Placebo sodium chloride injection A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort5: Placebo sodium chloride injection B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (2.5mg/kg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort6: Multiple dose ASC22 injection 1.0mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cohort6: Placebo sodium chloride injection A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ASC22</intervention_name>
    <description>200mg/1ml/1bottle</description>
    <arm_group_label>cohort1: Single dose ASC22 injection 0.3mg/kg</arm_group_label>
    <arm_group_label>cohort2:Single dose ASC22 injection 1.0mg/kg</arm_group_label>
    <arm_group_label>cohort3:Single dose ASC22 injection 2.5mg/kg</arm_group_label>
    <arm_group_label>cohort4: Multiple dose ASC22 injection 1.0mg/kg</arm_group_label>
    <arm_group_label>cohort5: Multiple dose ASC22 injection 2.5mg/kg</arm_group_label>
    <arm_group_label>cohort6: Multiple dose ASC22 injection 1.0mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sodium chloride</intervention_name>
    <description>90mg/10ml/1 bottle</description>
    <arm_group_label>cohort4: Placebo sodium chloride injection A</arm_group_label>
    <arm_group_label>cohort5: Placebo sodium chloride injection B</arm_group_label>
    <arm_group_label>cohort6: Placebo sodium chloride injection A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 18-65 years old (including boundary value), gender unlimited；&#xD;
&#xD;
          2. Chronic hepatitis B patients with clear diagnosis of Hematology, etiology and clinical&#xD;
             (for example: HBsAg positive for more than 6 months);&#xD;
&#xD;
          3. HBV-DNA turns negative after treatment with nucleoside (acid) drugs;&#xD;
&#xD;
          4. cohort1-5:HBsAg≤ 10000 IU/mL; cohort6: HBsAg≤ 100 IU/mL;&#xD;
&#xD;
          5. HBeAg negative;&#xD;
&#xD;
          6. The fertile female subjects or the fertile male subjects agreed to take contraceptive&#xD;
             measures from 7 days before the first administration until 24 weeks after the end of&#xD;
             the administration cycle of ASC22. The serum pregnancy test of fertile female subjects&#xD;
             must be negative within 7 days before the first administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with hepatitis a, hepatitis c (HCV RNA&gt;15IU/L), hepatitis d or HIV infection;&#xD;
             Patients with other active infections (e.g., respiratory tract infection, urinary&#xD;
             tract infection and herpes simplex, cytomegalovirus, epstein-barr virus);&#xD;
&#xD;
          2. Fibrosis stage: Cirrhosis, portal hypertension, or advanced fibrosis (defined as&#xD;
             Fibroscan≥9.5kPa or ARFI≥1.81m/sec or Fibrosis-4 (FIB-4)≥3.25 or METAVIR F≥3);&#xD;
&#xD;
          3. Liver cancer patients or blood AFP&gt;1×ULN;&#xD;
&#xD;
          4. cohort1-5：Patients who received interferon therapy within 6 months before the first&#xD;
             administration; cohort6: Patients who received interferon therapy before the first&#xD;
             administration;&#xD;
&#xD;
          5. Patients receiving immunosuppressive therapy within 3 months before the first&#xD;
             administration (except interferon);&#xD;
&#xD;
          6. The investigator judges that the participants are not suitable for this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Guiqiang Wang, MD</last_name>
    <phone>86-13911405123</phone>
    <email>john131212@sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jun Li, MD</last_name>
    <phone>86-13520089612</phone>
    <email>lijun1350089612@sina.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guiqiang Wang, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>October 9, 2022</last_update_submitted>
  <last_update_submitted_qc>October 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Hepatitis b (CHB)</keyword>
  <keyword>PD-L1</keyword>
  <keyword>Fc fusion protein injection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04465890
org study id: ASC-ASC22-II-CTP-01
nct id: NCT04465890
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to evaluate the safety and efficacy of ASC22 in the treatment
      of chronic hepatitis B after single and multiple drug administration.
The study consists of two parts: the ASC22 single-dose IIa study and the ASC22 multi-dose IIb
      study. The IIa study consists of 3 cohorts of 0.3mg/kg, 1.0mg/kg and 2.5mg/kg, and the IIb
      study consists of 2 cohorts of 1.0mg/kg and 2.5mg/kg. The objective is to evaluate the
      safety, tolerance and efficacy of ASC22 in patients with chronic hepatitis B (CHB), and to
      provide a guidance for the determination of dosage regimen.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Evaluate the decreased HBsAg levels at 12 or 24 weeks of treatment or at 4, 12, or 24 weeks of follow-up visits compared with baseline.
time frame: 48 weeks
description: Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
measure: Evaluate the number of patients with ≥0.5log reduction in HBsAg log10IU/ mL at 12 or 24 weeks of treatment, or at 4, 12, or 24 weeks of follow-up visits compared with baseline.
time frame: 48 weeks
description: Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
measure: Evaluate the decline value of HBsAg level.
time frame: 48 weeks
description: Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
measure: Evaluate the propotion's change of HBsAg < 0.05IU/ml in each cohort.
time frame: 48 weeks
description: Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
measure: Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort.
time frame: 48 weeks
description: Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
measure: Evaluate the changes of peripheral blood lymphocyte subsets in each cohort.
time frame: 48 weeks
description: Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
arm group label: cohort1: Single dose ASC22 injection 0.3mg/kg
arm group type: Experimental
description: Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once.
arm group label: cohort2:Single dose ASC22 injection 1.0mg/kg
arm group type: Experimental
description: Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once.
arm group label: cohort3:Single dose ASC22 injection 2.5mg/kg
arm group type: Experimental
description: Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once.
arm group label: cohort4: Multiple dose ASC22 injection 1.0mg/kg
arm group type: Experimental
description: Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
arm group label: cohort5: Multiple dose ASC22 injection 2.5mg/kg
arm group type: Experimental
description: Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks
arm group label: cohort4: Placebo sodium chloride injection A
arm group type: Placebo Comparator
description: Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg).
arm group label: cohort5: Placebo sodium chloride injection B
arm group type: Placebo Comparator
description: Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (2.5mg/kg).
arm group label: cohort6: Multiple dose ASC22 injection 1.0mg/kg
arm group type: Experimental
description: Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
arm group label: cohort6: Placebo sodium chloride injection A
arm group type: Placebo Comparator
description: Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg).
intervention type: Drug
intervention name: ASC22
description: 200mg/1ml/1bottle
arm group label: cohort1: Single dose ASC22 injection 0.3mg/kg
arm group label: cohort2:Single dose ASC22 injection 1.0mg/kg
arm group label: cohort3:Single dose ASC22 injection 2.5mg/kg
arm group label: cohort4: Multiple dose ASC22 injection 1.0mg/kg
arm group label: cohort5: Multiple dose ASC22 injection 2.5mg/kg
arm group label: cohort6: Multiple dose ASC22 injection 1.0mg/kg
intervention type: Drug
intervention name: sodium chloride
description: 90mg/10ml/1 bottle
arm group label: cohort4: Placebo sodium chloride injection A
arm group label: cohort5: Placebo sodium chloride injection B
arm group label: cohort6: Placebo sodium chloride injection A
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Guiqiang Wang, MD
phone: 86-13911405123
email: john131212@sina.com
last name: Jun Li, MD
phone: 86-13520089612
email: lijun1350089612@sina.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
sharing ipd: Undecided