Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in Humans
Condition: Treatment of Acute Zika Virus Infection
MeSH terms: Zika Virus Infection
Study type: Interventional
Phase: Phase 1

Summary: 
      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, first in human, time-lagged, parallel-group, single dose ascending (6 dose
      cohorts), Tyzivumab, ZIKV monoclonal antibody (mAb), study to be conducted in 24 flaviviral
      naïve healthy adult volunteers.

      Tyzivumab will be administered once through single IV infusion over 30 minutes. Total
      duration of study participation is estimated at approximately 98 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 safety of Tyzivumab in healthy adult
      volunteers through assessment of subject vital signs, clinical laboratory results, ECG,
      presence/absence of AE/SAE, PK and ADA.
    

Detailed description: 
      Dose escalation in this study will include 24 healthy volunteers in six (6) dose cohorts:

        -  0.2 mg/kg, N = 2

        -  0.5 mg/kg, N = 2

        -  1 mg/kg, N = 2

        -  5 mg/kg, N = 6

        -  10 mg/kg, N = 6

        -  20 mg/kg, N = 6

      A minimum of 20-hour interval from the first dosing must take place before the second subject
      can be dosed within each cohort. No such time interval will be required for dosing of
      subsequent subjects (third subject onwards) within the same cohort.

      Dose escalations will be guided by review of clinical signs, adverse events (AEs), and
      laboratory tests of the prior group (up to Day 7 after dosing) by a safety monitoring
      committee.

      In order to assess the safety and tolerability of an intravenous (IV) infusion of Tyzivumab
      when given to healthy adult volunteers, the following vital signs and tests will be
      performed:

        -  Blood Pressure

        -  Pulse Rate

        -  Respiratory Rate

        -  Body Temperature

        -  ECG

        -  Urinalysis

        -  Serum Chemistry

        -  Haematology

      In order to assess Tyzivumab pharmacokinetics (only for doses 1 mg/kg, 5 mg/kg, 10 mg/kg & 20
      mg/kg), the following parameters will be measured:

        -  maximum concentration (Cmax)

        -  time to maximum concentration (Tmax)

        -  area under the curve extrapolated to infinity (AUC0-∞)

        -  AUC calculated from time of administration to the last measurable concentration
           (AUC0-last)

        -  half-life (t1/2)

        -  volume of distribution (Vd)

        -  clearance [CL] in serum PK will be assessed at pre-dose, 0.5 h, 1 h, 2 h, 4 h, 8 h, 24
           h, 48 h, 72 h, 120 h, Day 7, Day 14, Day 28, Day 56 and Day 84.

      The presence and extent of anti-drug antibody (ADA) production in response to dosing with
      Tyzivumab will also be assessed at pre-dose, Day 14, Day 56 and Day 84.
    

Intervention name(s): Tyzivumab
Intervention type(s): Drug
Intervention description(s): Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other intervention name(s): TY008
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Time Lagged, Parallel-Group, Single Ascending Dose Study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Zika virus; Tyzivumab; Monoclonal antibody; Infectious diseases; Phase 1A first in human study; Singapore