Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in Humans

April 8, 2019 updated by: Tychan Pte Ltd.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore, 169608
        • Singhealth Investigational Medicine Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Each subject must meet all the following criteria to be enrolled:

  1. Adult healthy volunteers, aged 21 to 45, men or women

    a. Women must fulfil one (1) of the following criteria: i. Post-menopausal; either amenorrhea ≥ 12 months or follicle stimulating hormone > 40 mIU/mL ii. Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation iii.Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening day until 100 days post-infusion b. Male subjects who are non-vasectomized (or vasectomized less than six (6) months prior to dosing) and have female partners of childbearing potential must be willing to use an effective birth control method when having heterosexual intercourse, from screening day until 100 days post-infusion

  2. Subjects negative for antibodies to flaviviruses as measured by a commercially available Dengue virus IgG enzyme-linked immunosorbent assay (ELISA) diagnostic kit
  3. Subjects negative for human immunodeficiency virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV)
  4. Subjects who are willing to comply with the requirements of the study protocol and attend scheduled visit
  5. Subjects who give written informed consent approved by the Ethical Review Board governing the site
  6. Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations that are acceptable for study entry
  7. Accessible vein in the forearm for blood collection

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

  1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders
  2. Evidence of clinically significant anaemia (HB < 10 g/dL) or any other significant active haematological disease, or having donated > 450 mL of blood within the past three (3) months
  3. Evidence of substance abuse, or previous substance abuse
  4. Participation or planned participation in a study involving the administration of an investigational compound within the past four (4) months or during this study period
  5. Planned administration of any vaccine not foreseen by the study protocol 12 weeks before first dosing day and up to four (4) months after dosing
  6. Receipt of immunoglobulins and/or any blood products within nine (9) months of study enrolment or planned administration of any of these products during the study period
  7. History of any reaction to monoclonal antibodies
  8. Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception
  9. Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the subject

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 5 mg/kg
Subject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
Drug: Tyzivumab
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other Names:
  • TY008
EXPERIMENTAL: 10 mg/kg
Subject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
Drug: Tyzivumab
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other Names:
  • TY008
EXPERIMENTAL: 20 mg/kg
Subject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
Drug: Tyzivumab
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other Names:
  • TY008
EXPERIMENTAL: 0.2 mg/kg
Subject will be administered with 0.2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
Drug: Tyzivumab
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other Names:
  • TY008
EXPERIMENTAL: 0.5 mg/kg
Subject will be administered with 0.5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
Drug: Tyzivumab
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other Names:
  • TY008
EXPERIMENTAL: 1 mg/kg
Subject will be administered with 1 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.
Drug: Tyzivumab
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) Infused over 30 minutes
Other Names:
  • TY008

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability)
Time Frame: 84 days
Presence or absence of infusion reaction (hypersensitivity / anaphylaxis / etc.) in dose cohorts.
84 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Concentration (Cmax) - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate the maximum concentration (Cmax) of Tyzivumab in human serum.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate the time to maximum concentration (Tmax) of Tyzivumab in human serum.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Area Under the Curve Extrapolated to Infinity (AUC0-∞) - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate the area under the curve extrapolated to infinity (AUC0-∞) of Tyzivumab.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate the AUC calculated from time of administration to the last measurable concentration (AUC0-last) of Tyzivumab.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Half-Life (t1/2) - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate the half-life (t1/2) of Tyzivumab in human serum.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Volume of Distribution (Vd) - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate the volume of distribution (Vd) of Tyzivumab in human serum.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Clearance [CL] - Pharmacokinetic Assessment
Time Frame: Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate clearance [CL] of Tyzivumab in human serum.
Pre-dose, 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, 72 hour, 120 hour Day 7, Day 14, Day 28, Day 56 and Day 84.
Anti-Drug Antibody Assessment
Time Frame: Pre-dose, Day 14, Day 56 and Day 84
To assess the presence or absence of anti-drug antibody (ADA) production in response to dosing with Tyzivumab
Pre-dose, Day 14, Day 56 and Day 84

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tychan Pte Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National University Hospital, Singapore
National University, Singapore
Duke-NUS Graduate Medical School
Singapore Clinical Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jenny Low, MBBS, Singhealth Investigational Medicine Unit

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 8, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 12, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 4, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 8, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 23, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 10, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZKT-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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