Treatment of Acute Zika Virus Infection Clinical Trial
Official title:
Phase 1 First in Human, Time Lagged, Parallel-Group, Single Ascending Dose Study of Tyzivumab in Healthy Adult Volunteers
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.
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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Withdrawn |
NCT03776695 -
Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in ZIKV Infected Patients
|
Phase 1 |