<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/NCT03776695</url>
  </required_header>
  <id_info>
    <org_study_id>ZKT-002</org_study_id>
    <secondary_id>CTA1800062</secondary_id>
    <nct_id>NCT03776695</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in ZIKV Infected Patients</brief_title>
  <official_title>Phase 1 Time Lagged, Parallel-Group, Randomized, Placebo-Controlled, Single-Blind, Single Ascending Dose Study of Tyzivumab in ZIKV Infected Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tychan Pte Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Singapore Clinical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke-NUS Graduate Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tychan Pte Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Zika virus (ZIKV) infection is a new emerging arbovirus disease, caused by the same vector&#xD;
      that transmits Dengue virus, Aedes aegypti. ZIKV is a growing public health problem, rapidly&#xD;
      spreading throughout the continents since the first epidemic was reported in the French&#xD;
      Polynesian islands.&#xD;
&#xD;
      Currently, there are several ZIKV vaccine candidates in clinical trials. However, no ZIKV&#xD;
      therapy (biologic or small molecule) has advanced to clinical trials. Tyzivumab will be the&#xD;
      first therapeutic in the world, specifically targeting ZIKV, to enter clinical trials.&#xD;
&#xD;
      This is a Phase 1, time-lagged, parallel-group, randomized, placebo-controlled, single-blind,&#xD;
      single ascending dose, Tyzivumab, ZIKV monoclonal antibody (mAb), study to be conducted in&#xD;
      ZIKV polymerase chain reaction (PCR) positive patients.&#xD;
&#xD;
      Tyzivumab will be administered once through single IV infusion over 30 minutes. Total&#xD;
      duration of study participation is estimated at approximately 85 days from the date of&#xD;
      screening. Post-trial monitoring through weekly telephone calls will continue from Day 85&#xD;
      post-dose onwards for another three (3) more months.&#xD;
&#xD;
      The main objective of this study is to evaluate the safety of Tyzivumab in acutely infected&#xD;
      adult patients. Assessment of time taken to achieve negative ZIKV isolation from acute ZIKV&#xD;
      infected subjects' blood will be the study's secondary objectives.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dose escalation in this study will include 28 ZIKV-infected patients in four (4) dose&#xD;
      cohorts.&#xD;
&#xD;
      Eligible subjects will be enrolled into dose cohorts of seven (7) subjects each. Within each&#xD;
      dose cohort, subjects will be randomized to either Tyzivumab or Placebo Groups, with five (5)&#xD;
      subjects receiving Tyzivumab and two (2) receiving Placebo per cohort. There will be up to&#xD;
      four (4) dose levels / cohorts, for a total of 28 subjects. The proposed doses to be studied&#xD;
      are 2, 5, 10, and 20 mg/kg.&#xD;
&#xD;
      Within each dose cohort, a minimum of 48-hour interval is required between Tyzivumab dosing&#xD;
      of subject 1 and 2 and between subject 2 and 3, and a minimum of 24-hour interval is required&#xD;
      between Tyzivumab dosing of subject 3 and 4 and between subject 4 and 5. No such time&#xD;
      interval will be required for the Placebo dosing of subjects (i.e. a Placebo subject can be&#xD;
      dosed concurrently with or immediately after a Tyzivumab treatment subject). Dosing of the&#xD;
      last dose cohort (20 mg/kg) is optional if a trend of reduction in viral load and viral&#xD;
      isolation has been observed in dose level 1 (2 mg/kg), 2 (5 mg/kg) or 3 (10 mg/kg).&#xD;
&#xD;
      Dose escalations will be guided by review of clinical signs, adverse events (AEs), and&#xD;
      laboratory tests (including viral titre data) of the prior group (up to Day 7 after dosing)&#xD;
      by a safety monitoring committee. Safety analysis (up to Day 7) will also be completed for&#xD;
      the equivalent dose of ZKT-001 prior to the commencement of dosing in ZKT-002 for each&#xD;
      specified dose.&#xD;
&#xD;
      PD, PK and ADA measurements will be conducted at various time points throughout the study.&#xD;
      Subjects will be followed for up to approximately Day 84 safety and tolerability assessment.&#xD;
      Serum samples for PD, PK and ADA assessments, and urine samples for PD assessments will be&#xD;
      taken at specified time points.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of Zika infected patients&#xD;
  </why_stopped>
  <start_date type="Actual">October 9, 2018</start_date>
  <completion_date type="Actual">January 5, 2022</completion_date>
  <primary_completion_date type="Actual">January 5, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability)</measure>
    <time_frame>84 Days</time_frame>
    <description>Presence or absence of infusion reaction (hypersensitivity / anaphylaxis / etc.) in dose cohorts.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Viral Clearance Post-Tyzivumab Infusion (Efficacy)</measure>
    <time_frame>84 Days</time_frame>
    <description>Time taken to achieve ZIKV clearance (CL) from blood via negative virus isolation in subjects acutely infected with ZIKV when given an IV infusion of Tyzivumab</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Treatment of Acute Zika Virus Infection</condition>
  <arm_group>
    <arm_group_label>2 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered with 2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2 mg/kg - Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5 mg/kg - Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10 mg/kg - Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>20 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>20 mg/kg - Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tyzivumab</intervention_name>
    <description>Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb)</description>
    <arm_group_label>10 mg/kg</arm_group_label>
    <arm_group_label>2 mg/kg</arm_group_label>
    <arm_group_label>20 mg/kg</arm_group_label>
    <arm_group_label>5 mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% Saline</description>
    <arm_group_label>10 mg/kg - Placebo</arm_group_label>
    <arm_group_label>2 mg/kg - Placebo</arm_group_label>
    <arm_group_label>20 mg/kg - Placebo</arm_group_label>
    <arm_group_label>5 mg/kg - Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult volunteers, aged 21 to 60, men or women&#xD;
&#xD;
             a. Women must fulfil one (1) of the following criteria: i. Post-menopausal; either&#xD;
             amenorrhea ≥ 12 months or follicle stimulating hormone &gt; 40 mIU/mL ii. Surgically&#xD;
             sterile; hysterectomy, bilateral oophorectomy, or tubal ligation iii. Women of&#xD;
             childbearing potential participating in heterosexual sexual relations must be willing&#xD;
             to use adequate contraception from screening day until 100 days post-infusion b. Male&#xD;
             subjects who are non-vasectomized (or vasectomized less than six (6) months prior to&#xD;
             dosing) and have female partners of childbearing potential must be willing to use an&#xD;
             effective birth control method when having heterosexual intercourse, from screening&#xD;
             day until 100 days post-infusion&#xD;
&#xD;
          2. Any one or a combination of symptoms and signs suggestive of ZIKV acute infection,&#xD;
             presenting within 48 hours from onset&#xD;
&#xD;
          3. Positive ZIKV PCR for acute ZIKV infection&#xD;
&#xD;
          4. Subjects who are willing to comply with the requirements of the study protocol and&#xD;
             attend scheduled visit&#xD;
&#xD;
          5. Subjects who give written informed consent approved by the Ethical Review Board&#xD;
             governing the site&#xD;
&#xD;
          6. Satisfactory baseline medical assessment as assessed by physical examination and&#xD;
             normal laboratory values or minor variations that are acceptable for study entry&#xD;
&#xD;
          7. Accessible vein in the forearm for blood collection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,&#xD;
             neuropsychiatric, or immunosuppressive disorders&#xD;
&#xD;
          2. Evidence of clinically significant anaemia (HB &lt; 10 g/dL) or any other significant&#xD;
             active haematological disease, or having donated &gt; 450 mL of blood within the past&#xD;
             three (3) months&#xD;
&#xD;
          3. Evidence of substance abuse, or previous substance abuse&#xD;
&#xD;
          4. Participation or planned participation in a study involving the administration of an&#xD;
             investigational compound within the past four (4) months or during this study period&#xD;
&#xD;
          5. Planned administration of any vaccine not foreseen by the study protocol 12 weeks&#xD;
             before first dosing day and up to four (4) months after dosing&#xD;
&#xD;
          6. Receipt of immunoglobulins and/or any blood products within nine (9) months of study&#xD;
             enrolment or planned administration of any of these products during the study period&#xD;
&#xD;
          7. History of any reaction to monoclonal antibodies&#xD;
&#xD;
          8. Pregnant or lactating women, or women of childbearing potential who are unwilling to&#xD;
             use adequate contraception&#xD;
&#xD;
          9. Any condition that, in the opinion of the investigator, would complicate or compromise&#xD;
             the study or well-being of the subject&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jenny Low, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SingHealth Investigational Medicine Unit</name>
      <address>
        <city>Singapore</city>
        <zip>169608</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>March 8, 2022</last_update_submitted>
  <last_update_submitted_qc>March 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 24, 2022</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>Zika Virus Infection</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03776695
org study id: ZKT-002
secondary id: CTA1800062
nct id: NCT03776695
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Zika virus (ZIKV) infection is a new emerging arbovirus disease, caused by the same vector
      that transmits Dengue virus, Aedes aegypti. ZIKV is a growing public health problem, rapidly
      spreading throughout the continents since the first epidemic was reported in the French
      Polynesian islands.

      Currently, there are several ZIKV vaccine candidates in clinical trials. However, no ZIKV
      therapy (biologic or small molecule) has advanced to clinical trials. Tyzivumab will be the
      first therapeutic in the world, specifically targeting ZIKV, to enter clinical trials.

      This is a Phase 1, time-lagged, parallel-group, randomized, placebo-controlled, single-blind,
      single ascending dose, Tyzivumab, ZIKV monoclonal antibody (mAb), study to be conducted in
      ZIKV polymerase chain reaction (PCR) positive patients.

      Tyzivumab will be administered once through single IV infusion over 30 minutes. Total
      duration of study participation is estimated at approximately 85 days from the date of
      screening. Post-trial monitoring through weekly telephone calls will continue from Day 85
      post-dose onwards for another three (3) more months.

      The main objective of this study is to evaluate the safety of Tyzivumab in acutely infected
      adult patients. Assessment of time taken to achieve negative ZIKV isolation from acute ZIKV
      infected subjects' blood will be the study's secondary objectives.
Dose escalation in this study will include 28 ZIKV-infected patients in four (4) dose
      cohorts.

      Eligible subjects will be enrolled into dose cohorts of seven (7) subjects each. Within each
      dose cohort, subjects will be randomized to either Tyzivumab or Placebo Groups, with five (5)
      subjects receiving Tyzivumab and two (2) receiving Placebo per cohort. There will be up to
      four (4) dose levels / cohorts, for a total of 28 subjects. The proposed doses to be studied
      are 2, 5, 10, and 20 mg/kg.

      Within each dose cohort, a minimum of 48-hour interval is required between Tyzivumab dosing
      of subject 1 and 2 and between subject 2 and 3, and a minimum of 24-hour interval is required
      between Tyzivumab dosing of subject 3 and 4 and between subject 4 and 5. No such time
      interval will be required for the Placebo dosing of subjects (i.e. a Placebo subject can be
      dosed concurrently with or immediately after a Tyzivumab treatment subject). Dosing of the
      last dose cohort (20 mg/kg) is optional if a trend of reduction in viral load and viral
      isolation has been observed in dose level 1 (2 mg/kg), 2 (5 mg/kg) or 3 (10 mg/kg).

      Dose escalations will be guided by review of clinical signs, adverse events (AEs), and
      laboratory tests (including viral titre data) of the prior group (up to Day 7 after dosing)
      by a safety monitoring committee. Safety analysis (up to Day 7) will also be completed for
      the equivalent dose of ZKT-001 prior to the commencement of dosing in ZKT-002 for each
      specified dose.

      PD, PK and ADA measurements will be conducted at various time points throughout the study.
      Subjects will be followed for up to approximately Day 84 safety and tolerability assessment.
      Serum samples for PD, PK and ADA assessments, and urine samples for PD assessments will be
      taken at specified time points.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability)
time frame: 84 Days
description: Presence or absence of infusion reaction (hypersensitivity / anaphylaxis / etc.) in dose cohorts.
measure: Viral Clearance Post-Tyzivumab Infusion (Efficacy)
time frame: 84 Days
description: Time taken to achieve ZIKV clearance (CL) from blood via negative virus isolation in subjects acutely infected with ZIKV when given an IV infusion of Tyzivumab
arm group label: 2 mg/kg
arm group type: Experimental
description: Subject will be administered with 2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
arm group label: 2 mg/kg - Placebo
arm group type: Placebo Comparator
description: Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.
arm group label: 5 mg/kg
arm group type: Experimental
description: Subject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
arm group label: 5 mg/kg - Placebo
arm group type: Placebo Comparator
description: Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.
arm group label: 10 mg/kg
arm group type: Experimental
description: Subject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
arm group label: 10 mg/kg - Placebo
arm group type: Placebo Comparator
description: Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.
arm group label: 20 mg/kg
arm group type: Experimental
description: Subject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
arm group label: 20 mg/kg - Placebo
arm group type: Placebo Comparator
description: Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.
intervention type: Biological
intervention name: Tyzivumab
description: Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb)
arm group label: 10 mg/kg
arm group label: 2 mg/kg
arm group label: 20 mg/kg
arm group label: 5 mg/kg
intervention type: Other
intervention name: Placebo
description: 0.9% Saline
arm group label: 10 mg/kg - Placebo
arm group label: 2 mg/kg - Placebo
arm group label: 20 mg/kg - Placebo
arm group label: 5 mg/kg - Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jenny Low, MBBS
role: Principal Investigator
affiliation: Singapore General Hospital
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: Zika Virus Infection
sharing ipd: No