Currently, there are no licensed therapeutics against Zika virus infection. Due to this unmet medical need, Zika Virus Immune Globulin (ZIKV-IG) is being developed as a therapeutic intervention against Zika virus infection. In this first-in-human study, evaluation of ZIKV-IG safety and pharmacokinetics (absorption, metabolism and excretion) will be conducted in healthy adult volunteers.
This study will be evaluating safety and pharmacokinetics (PK) of one dose level of ZIKV-IG (50 mL) in healthy adult volunteers. The study is a single-center, double-blind, randomized and placebo-controlled design. The primary objective is to assess safety of intravenously (IV) administered ZIKV-IG, while the secondary objective is to determine the PK profile of ZIKV-IG in healthy adult volunteers. There will be a total of 30 subjects enrolled into the study; dosing of the first six subjects will be staggered over three separate days, wherein two subjects per day will be randomized 1:1 to either receive 50 mL of placebo IV or 50 mL of ZIKV-IG IV (the total amount of gamma immune globulin \[IgG\] protein from a single 50mL dose is 4.65g). After the first six subjects are dosed, the remaining 24 subjects will be randomized 2:1 to receive either ZIKV-IG or placebo. A safety monitoring committee will review safety data (collected up to 3 days post-dosing) of the first 12 dosed subjects prior to dosing of the remaining 18 subjects. Overall, there will be 19 subjects randomized to receive ZIKV-IG and 11 subjects randomized to receive placebo on Day 1. On Day 1 (post-dose at 1 hour, 3 hours, 8 hours) and Day 2, safety and PK assessments will be conducted while the subjects are in the Phase 1 clinic. After the discharge on Day 2, the subjects will come back to the clinic for safety and PK assessments on Days 3, 4, 6, 8, 10, 12, 15, 22, 29, 43, 57 and 85. Total study duration for each subject will be up to 4 months (from screening to Day 85).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
30
Zika Virus Immune Globulin (ZIKV-IG) is a human immune globulin preparation containing neutralizing antibodies to Zika virus.
Placebo is a normal saline solution (0.9% sodium chloride).
Syneos Health, Early Phase
Toronto, Ontario, Canada
Number of Subjects With Adverse Events.
Number of subjects with of adverse events by severity.
Time frame: Up to Day 85
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Maximum Concentration (Cmax)
Maximum observed serum concentration of Zika Virus Immune Globulin (ZIKV-IG)
Time frame: 0-2 hours predose to Day 85 postdose
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Time to Maximum Concentration (Tmax)
Time at which maximum serum concentration of Zika Virus Immune Globulin (ZIKV-IG) occurs.
Time frame: 0-2 hours predose up to Day 85 postdose
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Area Under the Curve Up to Last Quantifiable Concentration (AUC0-t)
Area under the concentration-time curve from time 0 to the last quantifiable serum Zika Virus Immune Globulin (ZIKV-IG) concentration.
Time frame: 0-2 hours predose to Day 85 postdose
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Area Under the Curve Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve from time 0 to the last quantifiable serum Zika Virus Immune Globulin (ZIKV-IG) concentration, plus the area extrapolated to infinity.
Time frame: 0-2 hours predose up to Day 85 postdose
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Clearance (CL)
Total body clearance of Zika Virus Immune Globulin (ZIKV-IG) following IV administration.
Time frame: 0-2 hours predose up to Day 85 postdose
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Half-Life (t1/2)
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Apparent first order terminal elimination half-life of Zika Virus Immune Globulin (ZIKV-IG).
Time frame: 0-2 hours predose up to Day 85 postdose
Assessment of Zika Virus Immune Globulin (ZIKV-IG) Volume of Distribution (Vz)
Volume of distribution of Zika Virus Immune Globulin (ZIKV-IG) following IV administration.
Time frame: 0-2 hours predose up to Day 85 postdose