<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/NCT04464733</url>
  </required_header>
  <id_info>
    <org_study_id>HRS9950-101</org_study_id>
    <nct_id>NCT04464733</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics(PK), Pharmacodynamics(PD) and Food Effect of HRS9950 in Healthy and CHB Subjects</brief_title>
  <official_title>A Phase I Study to Evaluate the Safety, Tolerability and PK, PD of Oral HRS9950 in Healthy Subjects With Single or Multiple Dose and Chronic Hepatitis B Patients With Multiple Dose, and Food Effects of HRS9950 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine 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 study is a randomized, Double-Blind, Placebo-Controlled study to evaluate the safety,&#xD;
      tolerability and pharmacokinetics, pharmacodynamics and food effect of HRS9950. The study&#xD;
      will be conducted in three parts sequentially:&#xD;
&#xD;
      Part 1, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of single&#xD;
      and multiple doses of HRS9950 tablet in healthy subjects. Part 1 will consist of 64 healthy&#xD;
      subjects, 6 groups.&#xD;
&#xD;
      Part 2, evaluate food effect of HRS9950 in healthy subjects. Part 2 will consist of 14&#xD;
      healthy subjects, 1 group (one of groups in Part 1).&#xD;
&#xD;
      Part 3, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of multiple&#xD;
      doses of HRS9950 tablet in naïve and treatment-experienced chronic hepatitis B (CHB)&#xD;
      patients. Part 3 will consist of 40 CHB patients, 1 group for naïve patients and 3 groups for&#xD;
      treatment-experienced patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 15, 2020</start_date>
  <completion_date type="Anticipated">March 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>8 DAYS for Group A-E; 29 DAYS for Group F; 50 DAYS for Group G-J</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration [Cmax]</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration time curve [AUC]</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to maximum plasma concentration [Tmax]</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent clearance [CL/F]</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Half-time [t1/2]</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent volume of distribution [Vz/F（Vd）]</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The concentration of IL-12p40 in the serum</measure>
    <time_frame>0-48 hours after each dose for Group A-J</time_frame>
    <description>After single or multiple administration of HRS9950</description>
  </primary_outcome>
  <number_of_arms>11</number_of_arms>
  <enrollment type="Anticipated">104</enrollment>
  <condition>Chronic Hepatitis b</condition>
  <arm_group>
    <arm_group_label>Treatment group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group F</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group C-</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group G</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group H</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment group J</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HRS9950</intervention_name>
    <description>Group A to Group E: dose 1-dose 5, single dose Group F: dose 2, multiple doses Group C-: dose 3 food effect Group G to Group J: dose 2-dose4, multiple doses</description>
    <arm_group_label>Treatment group A</arm_group_label>
    <arm_group_label>Treatment group B</arm_group_label>
    <arm_group_label>Treatment group C</arm_group_label>
    <arm_group_label>Treatment group C-</arm_group_label>
    <arm_group_label>Treatment group D</arm_group_label>
    <arm_group_label>Treatment group E</arm_group_label>
    <arm_group_label>Treatment group F</arm_group_label>
    <arm_group_label>Treatment group G</arm_group_label>
    <arm_group_label>Treatment group H</arm_group_label>
    <arm_group_label>Treatment group I</arm_group_label>
    <arm_group_label>Treatment group J</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Group A to Group J</description>
    <arm_group_label>Treatment group A</arm_group_label>
    <arm_group_label>Treatment group B</arm_group_label>
    <arm_group_label>Treatment group C</arm_group_label>
    <arm_group_label>Treatment group C-</arm_group_label>
    <arm_group_label>Treatment group D</arm_group_label>
    <arm_group_label>Treatment group E</arm_group_label>
    <arm_group_label>Treatment group F</arm_group_label>
    <arm_group_label>Treatment group G</arm_group_label>
    <arm_group_label>Treatment group H</arm_group_label>
    <arm_group_label>Treatment group I</arm_group_label>
    <arm_group_label>Treatment group J</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects&#xD;
&#xD;
               1. Signed informed consent.&#xD;
&#xD;
               2. Aged 18~55.&#xD;
&#xD;
               3. Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between&#xD;
                  18 to 28 kg/m2.&#xD;
&#xD;
               4. Vital signs, physical examination, laboratory results are within normal range or&#xD;
                  considered not clinically significant.&#xD;
&#xD;
               5. Female subjects (including partner) of childbearing potential must be using a&#xD;
                  medically acceptable form of birth control.&#xD;
&#xD;
          -  CHB subjects&#xD;
&#xD;
               1. Signed informed consent.&#xD;
&#xD;
               2. Aged 18~65.&#xD;
&#xD;
               3. CHB subjects should meet the following two criteria:&#xD;
&#xD;
               1. IgM HBcAb negative and HBsAg positive.&#xD;
&#xD;
               2. Two recorded HBsAg positive, and the time interval between the two tests was at&#xD;
                  least 6 months, one of which was the result of this screening 4.&#xD;
                  Treatment-experienced CHB subjects should also meet the following criteria:&#xD;
&#xD;
               1. Have received nucleoside analogue treatment for at least 6 months&#xD;
&#xD;
               2. HBeAg positive or negative, and the HBV DNA concentration should be less than 20&#xD;
                  IU/mL for at least 6 months before enrollment&#xD;
&#xD;
               3. Confirm ALT &lt;1.5 ULN (upper limit of normal value) by two measurements within 6&#xD;
                  months before enrollment 5. Treatment-naïve CHB subjects should also meet the&#xD;
                  following criteria:&#xD;
&#xD;
               1. Have not received antiviral therapy (nucleosides or interferons) at screening&#xD;
&#xD;
               2. HBeAg positive or negative, and the HBV DNA concentration should be greater than&#xD;
                  2000 IU/mL for at least 6 months before enrollment&#xD;
&#xD;
               3. Confirm ALT&gt; 1 ULN by two measurements within 6 months before enrollment 6.&#xD;
                  Female subjects (including partner) of childbearing potential must be using a&#xD;
                  medically acceptable form of birth control.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects&#xD;
&#xD;
               1. Currently suffering from cardiovascular, liver, kidney, digestive, nervous,&#xD;
                  blood, thyroid or mental diseases.&#xD;
&#xD;
               2. Medical history of malignant tumor.&#xD;
&#xD;
               3. Have a digestive system disease or a medical history of severe digestive system&#xD;
                  disease.&#xD;
&#xD;
               4. Have severe infection, severe trauma or major surgical operations within 3&#xD;
                  months.&#xD;
&#xD;
               5. 12-ECG test have clinical significant abnormality or the QT interval (QTc) &gt; 450&#xD;
                  ms.&#xD;
&#xD;
               6. Clinical laboratory examinations or chest radiographs have clinical significant&#xD;
                  abnormality.&#xD;
&#xD;
               7. Have a medical history of immune-mediated diseases.&#xD;
&#xD;
               8. Screening for infectious diseases is positive (Including HBsAg, Anti-HCV, TPPA,&#xD;
                  Anti-HIV).&#xD;
&#xD;
               9. Suspected allergy to any ingredient in the study drug.&#xD;
&#xD;
              10. Have any drug that inhibits or induces liver metabolism within 1 month.&#xD;
&#xD;
              11. Take any prescription drugs, over-the-counter drugs and Chinese herbal medicines&#xD;
                  within 14 days before taking the study drug, or took any drugs within 5&#xD;
                  half-lives at the time of screening; plan to take other drugs during the test&#xD;
                  period.&#xD;
&#xD;
              12. Participated in clinical trials of any drug or medical device within 3 months&#xD;
                  before screening, or within 5 half-lives before screening.&#xD;
&#xD;
              13. Had donated blood or blood transfusion≥ 400 mL within 3 months prior to&#xD;
                  screening.&#xD;
&#xD;
              14. The average daily smoking ≥ 5 cigarettes within three months; the average daily&#xD;
                  alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer&#xD;
                  or 150 mL wine or 50 mL low-alcohol);&#xD;
&#xD;
              15. Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more&#xD;
                  than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the&#xD;
                  study; and those who have special dietary requirements and cannot follow the&#xD;
                  unified diet;&#xD;
&#xD;
              16. Pregnant or lactating women;&#xD;
&#xD;
              17. Drug screening or alcohol breath test is positive.&#xD;
&#xD;
              18. Other conditions that the investigator believes the subject is not suitable.&#xD;
&#xD;
          -  CHB subjects&#xD;
&#xD;
               1. Currently suffering from serious cardiovascular, liver, kidney, digestive,&#xD;
                  nervous, blood, thyroid or mental diseases other than hepatitis B.&#xD;
&#xD;
               2. People have acute or chronic liver disease by non-HBV infection.&#xD;
&#xD;
               3. Liver stiffness (LSM)&gt; 12.4 kPa by noninvasive transient liver elastography (eg&#xD;
                  Fibroscan®) or recorded liver biopsy suggesting cirrhosis or extensive fibrosis&#xD;
&#xD;
               4. Primary liver cancer, high-risk groups of primary liver cancer or AFP&gt; 50g/L;&#xD;
&#xD;
               5. Have clinically demonstrated or history of liver function decompensation,&#xD;
                  including but not limited to: hepatic encephalopathy, hepatorenal syndrome,&#xD;
                  splenomegaly, ascites, etc.;&#xD;
&#xD;
               6. Laboratory inspection:&#xD;
&#xD;
                    1. Platelet count &lt;90×109/L;&#xD;
&#xD;
                    2. White blood cell count &lt;3.0×109/L;&#xD;
&#xD;
                    3. Absolute value of neutrophils &lt;1.5×109/L;&#xD;
&#xD;
                    4. Serum total bilirubin&gt;2×ULN;&#xD;
&#xD;
                    5. Albumin &lt;30 g/L;&#xD;
&#xD;
                    6. Creatinine clearance rate ≤60ml/min;&#xD;
&#xD;
                    7. INR&gt;1.5;&#xD;
&#xD;
                    8. ALT exceeds 5 times the upper limit of normal value on screening/baseline&#xD;
                       visit&#xD;
&#xD;
               7. HIV and/or syphilis antibody positive&#xD;
&#xD;
               8. Subjects who have previously received organ/bone marrow transplantation;&#xD;
&#xD;
               9. Have used immunosuppressants, immunomodulators or cytotoxic drugs within 6 months&#xD;
                  before the study medication;&#xD;
&#xD;
              10. Suspected allergy to any ingredient in the study drug.&#xD;
&#xD;
              11. The average daily smoking ≥ 5 cigarettes within three months; the average daily&#xD;
                  alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer&#xD;
                  or 150 mL wine or 50 mL low-alcohol);&#xD;
&#xD;
              12. Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more&#xD;
                  than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the&#xD;
                  study; and those who have special dietary requirements and cannot follow the&#xD;
                  unified diet;&#xD;
&#xD;
              13. Pregnant or lactating women;&#xD;
&#xD;
              14. Drug screening or alcohol breath test is positive.&#xD;
&#xD;
              15. Other conditions that the investigator believes the subject is not suitable.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Liping Ma</last_name>
    <phone>+86 13581669936</phone>
    <email>maliping@hrglobe.cn</email>
  </overall_contact>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 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>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</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/NCT04464733
org study id: HRS9950-101
nct id: NCT04464733
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is a randomized, Double-Blind, Placebo-Controlled study to evaluate the safety,
      tolerability and pharmacokinetics, pharmacodynamics and food effect of HRS9950. The study
      will be conducted in three parts sequentially:

      Part 1, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of single
      and multiple doses of HRS9950 tablet in healthy subjects. Part 1 will consist of 64 healthy
      subjects, 6 groups.

      Part 2, evaluate food effect of HRS9950 in healthy subjects. Part 2 will consist of 14
      healthy subjects, 1 group (one of groups in Part 1).

      Part 3, evaluate the safety, tolerability and pharmacokinetics, pharmacodynamics of multiple
      doses of HRS9950 tablet in naïve and treatment-experienced chronic hepatitis B (CHB)
      patients. Part 3 will consist of 40 CHB patients, 1 group for naïve patients and 3 groups for
      treatment-experienced patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Care Provider, Investigator)
measure: The incidence and severity of treatment-related adverse events as assessed by CTCAE v5.0
time frame: 8 DAYS for Group A-E; 29 DAYS for Group F; 50 DAYS for Group G-J
measure: Maximum Plasma Concentration [Cmax]
time frame: 0-48 hours after each dose for Group A-J
description: Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
measure: Area under the concentration time curve [AUC]
time frame: 0-48 hours after each dose for Group A-J
description: Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
measure: Time to maximum plasma concentration [Tmax]
time frame: 0-48 hours after each dose for Group A-J
description: Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
measure: Apparent clearance [CL/F]
time frame: 0-48 hours after each dose for Group A-J
description: Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
measure: Half-time [t1/2]
time frame: 0-48 hours after each dose for Group A-J
description: Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
measure: Apparent volume of distribution [Vz/F（Vd）]
time frame: 0-48 hours after each dose for Group A-J
description: Pharmacokinetic parameters of HRS9950, main metabolite and identified major metabolites in plasma
measure: The concentration of IL-12p40 in the serum
time frame: 0-48 hours after each dose for Group A-J
description: After single or multiple administration of HRS9950
arm group label: Treatment group A
arm group type: Experimental
arm group label: Treatment group B
arm group type: Experimental
arm group label: Treatment group C
arm group type: Experimental
arm group label: Treatment group D
arm group type: Experimental
arm group label: Treatment group E
arm group type: Experimental
arm group label: Treatment group F
arm group type: Experimental
arm group label: Treatment group C-
arm group type: Experimental
arm group label: Treatment group G
arm group type: Experimental
arm group label: Treatment group H
arm group type: Experimental
arm group label: Treatment group I
arm group type: Experimental
arm group label: Treatment group J
arm group type: Experimental
intervention type: Drug
intervention name: HRS9950
description: Group A to Group E: dose 1-dose 5, single dose Group F: dose 2, multiple doses Group C-: dose 3 food effect Group G to Group J: dose 2-dose4, multiple doses
arm group label: Treatment group A
arm group label: Treatment group B
arm group label: Treatment group C
arm group label: Treatment group C-
arm group label: Treatment group D
arm group label: Treatment group E
arm group label: Treatment group F
arm group label: Treatment group G
arm group label: Treatment group H
arm group label: Treatment group I
arm group label: Treatment group J
intervention type: Drug
intervention name: Placebo
description: Group A to Group J
arm group label: Treatment group A
arm group label: Treatment group B
arm group label: Treatment group C
arm group label: Treatment group C-
arm group label: Treatment group D
arm group label: Treatment group E
arm group label: Treatment group F
arm group label: Treatment group G
arm group label: Treatment group H
arm group label: Treatment group I
arm group label: Treatment group J
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Liping Ma
phone: +86 13581669936
email: maliping@hrglobe.cn
responsible party type: Sponsor
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic