Treatment of Acute Zika Virus InfectionPhase 1NCT03776695
Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in ZIKV Infected Patients
A Phase 1 study testing Tyzivumab in people with Treatment of Acute Zika Virus Infection, run by Tychan Pte Ltd. at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- Treatment of Acute Zika Virus Infection
- What is being tested?
- Tyzivumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteSingapore
- Study dates
- 9 Oct 2018to 5 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adult volunteers, aged 21 to 60, men or women
- 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
- Any one or a combination of symptoms and signs suggestive of ZIKV acute infection, presenting within 48 hours from onset
- Positive ZIKV PCR for acute ZIKV infection
- Subjects who are willing to comply with the requirements of the study protocol and attend scheduled visit
- Subjects who give written informed consent approved by the Ethical Review Board governing the site
- Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations that are acceptable for study entry
- Accessible vein in the forearm for blood collection
Who cannot join
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders
- 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
- Evidence of substance abuse, or previous substance abuse
- 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
- 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
- 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
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- History of any reaction to monoclonal antibodies
- Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception
- Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the subject
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Time Lagged, Parallel-Group, Randomized, Placebo-Controlled, Single-Blind, Single Ascending Dose Study of Tyzivumab in ZIKV Infected Patients
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Treatment of Acute Zika Virus Infection
- Being tested
- Tyzivumab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TyzivumabBiological
Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb)
PlaceboOther
0.9% Saline
| Study group | Role | What they receive |
|---|---|---|
| 2 mg/kg | Experimental | Subject will be administered with 2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. Receives: Biological: Tyzivumab |
| 2 mg/kg - Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. Receives: Other: Placebo |
| 5 mg/kg | Experimental | Subject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. Receives: Biological: Tyzivumab |
| 5 mg/kg - Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. Receives: Other: Placebo |
| 10 mg/kg | Experimental | Subject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. Receives: Biological: Tyzivumab |
| 10 mg/kg - Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. Receives: Other: Placebo |
| 20 mg/kg | Experimental | Subject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. Receives: Biological: Tyzivumab |
| 20 mg/kg - Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability)
Presence or absence of infusion reaction (hypersensitivity / anaphylaxis / etc.) in dose cohorts.
Measured: 84 Days
Secondary outcomes (1)
Viral Clearance Post-Tyzivumab Infusion (Efficacy)
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
Measured: 84 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2018
- Study start9 Oct 2018
- Primary completion5 Jan 2022
- Study completion5 Jan 2022
Why it stopped: Lack of Zika infected patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment of Acute Zika Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tychan Pte Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Singapore Clinical Research Institute, Duke-NUS Graduate Medical School
- Responsible party
- Sponsor
- Investigators
- Jenny Low, MBBS, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03776695
- Sponsor's protocol ID
- ZKT-002
- Other IDs
- CTA1800062
- Status last verified
- Mar 2022
- First submitted
- 12 Dec 2018
- Last updated
- 24 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Time Lagged, Parallel-Group, Randomized, Placebo-Controlled, Single-Blind, Single Ascending Dose Study of Tyzivumab in ZIKV Infected Patients
- ClinicalTrials.gov ID
- NCT03776695
- Acronym / sponsor ID
- ZKT-002
- Conditions
- Treatment of Acute Zika Virus Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of Zika infected patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Tychan Pte Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Singapore Clinical Research Institute, Duke-NUS Graduate Medical School
- Study start
- 9 Oct 2018 (actual)
- Primary completion
- 5 Jan 2022 (actual)
- Study completion
- 5 Jan 2022 (actual)
- First posted
- 17 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| 2 mg/kg | Experimental | Biological: TyzivumabSubject will be administered with 2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. |
| 2 mg/kg - Placebo | Placebo comparator | Other: PlaceboSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. |
| 5 mg/kg | Experimental | Biological: TyzivumabSubject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. |
| 5 mg/kg - Placebo | Placebo comparator | Other: PlaceboSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. |
| 10 mg/kg | Experimental | Biological: TyzivumabSubject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. |
| 10 mg/kg - Placebo | Placebo comparator | Other: PlaceboSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. |
| 20 mg/kg | Experimental | Biological: TyzivumabSubject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes. |
| 20 mg/kg - Placebo | Placebo comparator | Other: PlaceboSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Adult volunteers, aged 21 to 60, men or women
- Any one or a combination of symptoms and signs suggestive of ZIKV acute infection, presenting within 48 hours from onset
- Positive ZIKV PCR for acute ZIKV infection
- Subjects who are willing to comply with the requirements of the study protocol and attend scheduled visit
- Subjects who give written informed consent approved by the Ethical Review Board governing the site
Key exclusion criteria (9 listed)
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders
- 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
- Evidence of substance abuse, or previous substance abuse
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TyzivumabTyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb) | Biological | 10 mg/kg, 2 mg/kg, 20 mg/kg, 5 mg/kg |
| Placebo0.9% Saline | Other | 10 mg/kg - Placebo, 2 mg/kg - Placebo, 20 mg/kg - Placebo, 5 mg/kg - Placebo |
Primary outcome
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.
1 secondary outcome
Viral Clearance Post-Tyzivumab Infusion (Efficacy)
Time frame: 84 Days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jenny Low, MBBS principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tyzivumab in people with Treatment of Acute Zika Virus Infection, run by Tychan Pte Ltd. at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability) (time frame: 84 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2022; AzTrials last refreshed its copy on 8 Nov 2026.