Treatment of Acute Yellow Fever Virus InfectionPhase 1NCT03776786
Safety and Tolerability of an Antibody Against Yellow Fever Virus (TY014) in Humans
A Phase 1 study testing TY014 and 0.9% Saline in people with Treatment of Acute Yellow Fever Virus Infection, run by Tysana Pte Ltd at 1 site in Singapore.
Trial summary
Yellow Fever is an acute viral hemorrhagic disease caused by the Yellow Fever Virus (YFV), a re-emerging arbovirus transmitted by the same mosquito vector (Aedes aegypti) that transmits Dengue virus (DENV) and Zika virus (ZIKV). Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Treatment of Acute Yellow Fever Virus Infection
- What is being tested?
- TY014 and 0.9% Saline
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteSingapore
- Study dates
- 6 Dec 2018to 10 Oct 2019
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult volunteers, aged 21 to 50 years old, men or women
- Subjects negative for human immunodeficiency virus (HIV), Hepatitis B virus surface Antigen (HBsAg) and Hepatitis C virus (HCV)
- Subjects who have not been vaccinated against or had prior exposure to Yellow Fever Virus (YFV)
- Subjects who have no history of travels to Central America, South America, Africa or any other YF endemic countries, and have no plans to visit Central America, South America, Africa or any other YF endemic countries in the next six (6) months
- Subjects who are willing to comply with the requirements of the study protocol, attend scheduled visits and make themselves available for the duration of the study with access to a consistent means of telephone contact, which may be, but not limited to, at home or at work via landline or mobile
- Subjects who give written informed consent approved by the Ethical Review Board governing the site
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- Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. Normal laboratory values must be within normal range of the assessing site or show minor variations that are deemed not clinically significant as judged by the Investigator and acceptable for study entry. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event
- Accessible vein in the forearm for blood collection
- Female subjects of childbearing potential may be enrolled in the study if they have negative urine pregnancy tests on the day of screening and day of admission
- Female subjects of non-childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post-menopause subjects must have had at least 12 months of natural (spontaneous) amenorrhea
- Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) must agree to use adequate and reliable contraceptive measures (e.g. spermicides, condoms, contraceptive pills, etc.) or practice abstinence throughout the duration of the study (up to 84 days post-dosing)
Who cannot join
- Presence of acute infection in the preceding 14 days, or presence of a temperature ≥ 38.0 ˚C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of admission
- History of severe drug and / or food allergies and / or known allergies to the trial product or its components
- Female subject who is pregnant or breast-feeding
- 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
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- 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
- 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
- Administration of any licensed vaccine within 30 days before the first study vaccine dose.
- History of any reaction to monoclonal antibodies
- Any condition that, in the opinion of the Investigator, would complicate or compromise the study or well-being of the subject
- Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) who are unwilling to use adequate contraception or practice abstinence throughout the duration of the study (up to 84 days post-dosing)
- Efficacy Arm (1B) only:
- Subjects meeting any of the following criteria will be excluded from the study:
- Planned travels to Central America, South America, Africa or any other YFV-endemic countries in the next six (6) months
- History of thymus gland disease.
- Diagnosed with cancer or on treatment for cancer with the three (3) years prior to the screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 First-in-Human, Time Lagged, Single Ascending Dose Study of TY014 in Healthy Adult Volunteers (Safety Arm - 1A) and Sequential Time Lagged, Parallel-Group, Randomised, Placebo-Controlled, Double-Blind, Single Ascending Dose Study of TY014 in YF-17D Vaccine Strain-Challenged Healthy Adult Volunteers (Efficacy Arm - 1B)
Yellow Fever is an acute viral hemorrhagic disease caused by the Yellow Fever Virus (YFV), a re-emerging arbovirus transmitted by the same mosquito vector (Aedes aegypti) that transmits Dengue virus (DENV) and Zika virus (ZIKV). YFV is endemic in tropical and subtropical areas of South America and Africa, causing an estimated 200,000 infections and 30,000 deaths annually. It has now become a growing public health problem, rapidly spreading throughout the two (2) continents in a cyclical pattern. With climate change, global travel and urbanisation, which increase the chance for mosquito-borne diseases to spread rapidly, the risk of YFV establishing its foothold in the Asia-Pacific region with periodic epidemic bursts remains a real public health concern.
Although there is currently a safe and effective vaccine available on the market, global shortages of supplies have severely hampered any efforts in the prevention and control of YFV outbreaks. To date, no YFV therapy (biologic or small molecule) has advanced to clinical trials. TY014 will be the first therapeutic in the world, specifically targeting YFV, to enter clinical trials. It is anticipated that a monoclonal antibody therapeutic could be administered to infected cases to reduce disease severity within the patient and their contacts.
Read more
This is a Phase 1, first-in-human TY014, YFV monoclonal antibody (mAb), study to be conducted in two (2) arms:
- Safety Arm (1A): Healthy adult volunteers
- Efficacy Arm (1B): Healthy adult volunteers challenged with YF-17D Vaccine Strain 24 hours prior to TY014 dosing
TY014 will be administered once through single IV infusion over 30 minutes. Total duration of study participation is estimated at approximately 114 days from the date of screening.
The main objectives of this study are to: (a) evaluate the safety of TY014 in healthy adult volunteers, and (b) evaluate the safety of TY014 in YF-17D Vaccine Strain-challenged healthy adult volunteers. Percentage aviremia of YF-17D Vaccine Strain-challenged subjects within 48 hours after IV infusion of TY014 will also be assessed.
Read the detailed description
Safety Arm (1A):
Safety Arm is a phase 1A First-in-Human, Time Lagged, Single Ascending Dose Study of TY014 in Healthy Adult Volunteers.
Safety, tolerability and PK of TY014 will be assessed. The dose escalation will include 27 healthy volunteers in five (5) dose cohorts:
- 0.5 mg/kg, N = 2 TY014 + 5 Placebos
- 2 mg/kg, N = 5 TY014
- 5 mg/kg, N = 5 TY014
- 10 mg/kg, N = 5 TY014
- 20 mg/kg, N = 5 TY014 Subjects will be required to be inpatient at the trial site for approximately 72 hours.
Dose escalations will be guided by a safety review of clinical signs, adverse events (AEs), and laboratory tests (excluding lipase) of the prior group (up to 48 hours post-dose for cohort 1, and up to Day 7 post-dose for cohorts 2 - 5).
A minimum of 20-hour interval from the first TY014 treatment subject dosing must take place before the second TY014 treatment subject can be dosed within each cohort. No such time interval will be required for dosing of subsequent TY014 treatment subjects (third subject onwards) within the same cohort, as well as Placebo dosing in dose cohort 1 (i.e. all five placebos can be dosed at the same time).
After 72 hours, subjects will be discharged from trial site and to return for scheduled follow-up visits.
Subjects will be followed for up to approximately Day 84 for PK sampling, with serum samples taken at specified times.
Dose escalations for the Safety (1A) Arm will be guided by a safety review of clinical signs, adverse events (AEs), and laboratory tests (excluding lipase) of the prior dose cohort (up to Day 7).
Similar safety review (up to Day 7) will also be completed for the equivalent dose in Safety Arm (1A) prior to the commencement of the Efficacy Arm (1B) for each specified dose.
Efficacy Arm (1B):
Efficacy Arm is a phase 1B Sequential Time Lagged, Parallel-Group, Randomised, Placebo-Controlled, Double-Blind, Single Ascending Dose Study of TY014 in YF-17D Vaccine Strain-Challenged Healthy Adult Volunteers.
Safety, tolerability and time to achieve aviremia through negative YFV isolation from blood in YF-17D Vaccine Strain-challenged healthy adult volunteers when given an IV infusion of TY014 will be assessed.
Eligible subjects will be randomised into TY014 or Placebo Group in each cohort.
The dose escalation will include up to 40 healthy volunteers in up to four (4) dose cohorts:
- 2 mg/kg, N = 5 TY014 + 5 Placebos
- 5 mg/kg, N = 5 TY014 + 5 Placebos
- 10 mg/kg, N = 5 TY014 + 5 Placebos
- 20 mg/kg, N = 5 TY014 + 5 Placebos Efficacy Arm (1B) will be based on an adaptive trial design, with ten (10) YF-17D vaccinated subjects from each dose cohort being randomised 1:1 into either TY014 or Placebo group, five (5) subjects in each group. After TY014 or placebo administration, safety and efficacy of TY014 in YF-17D Vaccine Strain-Challenged subjects will be assessed.
- If current dose of TY014 shows safety but not efficacy*, Efficacy Arm (1B) will escalate to the next dose cohort. ii) If current dose of TY014 is safe and efficacious*, efficacious dose of TY014 is established and the Efficacy Arm (1B) of the trial is completed.
*Efficacy of TY014 is defined as aviremia by virus isolation being observed in 100% of vaccinated subjects within 48 hours post-dosing.
Subjects will be required to be inpatient at the trial site for approximately 96 hours.
Subjects will be vaccinated with the YF-17D Vaccine on Day -1. On Day 0, 24 hours after vaccination, subjects will then be administered TY014 or Placebo.
A minimum of 20-hour interval from the first two (2) subjects dosing (1 treatment and 1 placebo concurrently) must take place before the third subject can be dosed within each cohort. No such time interval will be required for dosing of subsequent subjects (fourth subject onwards) within the same cohort.
After 96 hours, subjects will be discharged from trial site and are to return for scheduled follow-up visits.
PD and PK measurements will be conducted at various time points throughout the study. Subjects will be followed for up to approximately Day 84 post-dose. Samples for PD (serum and urine) and PK (serum) assessments will be taken at specified time points.
Dose escalations for the Efficacy (1B) Arm will be guided by a safety review of clinical signs, adverse events (AEs), laboratory tests (excluding lipase) and presence of viremia (via virus isolation) of the prior dose cohort (up to Day 14). Escalation to the next dose cohort (e.g. from dose cohort 1 (2 mg/kg) to dose cohort 2 (5 mg/kg), from dose cohort 2 (5 mg/kg) to dose cohort 3 (10 mg/kg) and from dose cohort 3 (10 mg/kg) to dose cohort 4 (20 mg/kg)) will only be conducted if from prior dose cohort (e.g. dose cohort 1 (2 mg/kg), dose cohort 2 (5 mg/kg) and dose cohort 3 (10 mg/kg) respectively):
- safety (up to Day 14 post-dose) has been established through a safety review, and
- presence of viremia (up to 48 hours post-dose) via virus isolation in any of the TY014-treated subjects.
- Being tested
- TY014, 0.9% Saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TY014Biological
TY014 Injection, (100 mg/5 mL/Vial), Yellow Fever Virus (YFV) Monoclonal Antibody (mAb)
0.9% SalineOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Safety Arm - 0.5 mg/kg | Experimental | Subject will be administered with 0.5 mg/kg of TY014 via IV infusion over a period of 30 minutes. Receives: Biological: TY014 |
| Safety Arm - Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. Receives: Other: 0.9% Saline |
| Safety Arm - 2 mg/kg | Experimental | Subject will be administered with 2 mg/kg of TY014 via IV infusion over a period of 30 minutes. Receives: Biological: TY014 |
| Safety Arm - 5 mg/kg | Experimental | Subject will be administered with 5 mg/kg of TY014 via IV infusion over a period of 30 minutes. Receives: Biological: TY014 |
| Safety Arm - 10 mg/kg | Experimental | Subject will be administered with 10 mg/kg of TY014 via IV infusion over a period of 30 minutes. Receives: Biological: TY014 |
| Safety Arm - 20 mg/kg | Experimental | Subject will be administered with 20 mg/kg of TY014 via IV infusion over a period of 30 minutes. Receives: Biological: TY014 |
| Efficacy Arm - 2 mg/kg | Experimental | Subject will be administered with 2 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Biological: TY014 |
| Efficacy Arm - 2 mg/kg Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Other: 0.9% Saline |
| Efficacy Arm - 5 mg/kg | Experimental | Subject will be administered with 5 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Biological: TY014 |
| Efficacy Arm - 5 mg/kg Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Other: 0.9% Saline |
| Efficacy Arm - 10 mg/kg | Experimental | Subject will be administered with 10 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Biological: TY014 |
| Efficacy Arm - 10 mg/kg Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Other: 0.9% Saline |
| Efficacy Arm - 20 mg/kg | Experimental | Subject will be administered with 20 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Biological: TY014 |
| Efficacy Arm - 20 mg/kg Placebo | Placebo comparator | Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. Receives: Other: 0.9% Saline |
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
Percentage Aviremia Post Treatment (Efficacy Arm only)
Percentage of YF-17D Vaccine Strain-challenged healthy adult volunteers showing aviremia via virus isolation within 48 hours after given an IV infusion of TY014
Measured: 14 Days
Secondary outcomes (8)
Maximum Concentration (Cmax) - Pharmacokinetic Assessment
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 TY014 in human serum.
Measured: 84 Days
Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment
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 TY014 in human serum.
Measured: 84 Days
Area Under the Curve Extrapolated to Infinity (AUC0-∞) - Pharmacokinetic Assessment
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 TY014.
Measured: 84 Days
AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment
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 TY014.
Measured: 84 Days
Half-Life (t1/2) - Pharmacokinetic Assessment
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 TY014 in human serum.
Measured: 84 Days
Volume of Distribution (Vd) - Pharmacokinetic Assessment
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 TY014 in human serum.
Measured: 84 Days
Clearance [CL] - Pharmacokinetic Assessment
Constant monitoring of the levels of antibody in subject sera through various time points as stated below would help elucidate clearance [CL] of TY014 in human serum.
Measured: 84 Days
Viral Load Reduction (Efficacy Arm only)
Assess YFV viral load reduction from blood by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in YF-17D Vaccine Strain-challenged healthy adult volunteers when given an IV infusion of TY014.
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 start6 Dec 2018
- Primary completion1 Jul 2019
- Study completion10 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Treatment of Acute Yellow Fever 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tysana Pte Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jenny Low, MBBS, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03776786
- Sponsor's protocol ID
- YFT-001
- Other IDs
- CTA1800118
- Status last verified
- Oct 2019
- First submitted
- 12 Dec 2018
- Last updated
- 25 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Low JG, Ng JHJ, Ong EZ, Kalimuddin S, Wijaya L, Chan YFZ, Ng DHL, Tan HC, Baglody A, Chionh YH, Lee DCP, Budigi Y, Sasisekharan R, Ooi EE. Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody. N Engl J Med. 2020 Jul 30;383(5):452-459. doi: 10.1056/NEJMoa2000226.
PubMed 32726531
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 First-in-Human, Time Lagged, Single Ascending Dose Study of TY014 in Healthy Adult Volunteers (Safety Arm - 1A) and Sequential Time Lagged, Parallel-Group, Randomised, Placebo-Controlled, Double-Blind, Single Ascending Dose Study of TY014 in YF-17D Vaccine Strain-Challenged Healthy Adult Volunteers (Efficacy Arm - 1B)
- ClinicalTrials.gov ID
- NCT03776786
- Acronym / sponsor ID
- YFT-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Tysana Pte LtdIndustry (pharma, biotech, devices)
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- 1 Jul 2019 (actual)
- Study completion
- 10 Oct 2019 (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.
Yellow Fever is an acute viral hemorrhagic disease caused by the Yellow Fever Virus (YFV), a re-emerging arbovirus transmitted by the same mosquito vector (Aedes aegypti) that transmits Dengue virus (DENV) and Zika virus (ZIKV). YFV is endemic in tropical and subtropical areas of South America and Africa, causing an estimated 200,000 infections and 30,000 deaths annually. It has now become a growing public health problem, rapidly spreading throughout the two (2) continents in a cyclical pattern. With climate change, global travel and urbanisation, which increase the chance for mosquito-borne diseases to spread rapidly, the risk of YFV establishing its foothold in the Asia-Pacific region with periodic epidemic bursts remains a real public health concern.
Although there is currently a safe and effective vaccine available on the market, global shortages of supplies have severely hampered any efforts in the prevention and control of YFV outbreaks. To date, no YFV therapy (biologic or small molecule) has advanced to clinical trials. TY014 will be the first therapeutic in the world, specifically targeting YFV, to enter clinical trials. It is anticipated that a monoclonal antibody therapeutic could be administered to infected cases to reduce disease severity within the patient and their contacts.
This is a Phase 1, first-in-human TY014, YFV monoclonal antibody (mAb), study to be conducted in two (2) arms:
- Safety Arm (1A): Healthy adult volunteers
- Efficacy Arm (1B): Healthy adult volunteers challenged with YF-17D Vaccine Strain 24 hours prior to TY014 dosing
TY014 will be administered once through single IV infusion over 30 minutes. Total duration of study participation is estimated at approximately 114 days from the date of screening.
The main objectives of this study are to: (a) evaluate the safety of TY014 in healthy adult volunteers, and (b) evaluate the safety of TY014 in YF-17D Vaccine Strain-challenged healthy adult volunteers. Percentage aviremia of YF-17D Vaccine Strain-challenged subjects within 48 hours after IV infusion of TY014 will also be assessed.
Detailed description
Safety Arm (1A):
Safety Arm is a phase 1A First-in-Human, Time Lagged, Single Ascending Dose Study of TY014 in Healthy Adult Volunteers.
Safety, tolerability and PK of TY014 will be assessed. The dose escalation will include 27 healthy volunteers in five (5) dose cohorts:
- 0.5 mg/kg, N = 2 TY014 + 5 Placebos
- 2 mg/kg, N = 5 TY014
- 5 mg/kg, N = 5 TY014
- 10 mg/kg, N = 5 TY014
- 20 mg/kg, N = 5 TY014 Subjects will be required to be inpatient at the trial site for approximately 72 hours.
Dose escalations will be guided by a safety review of clinical signs, adverse events (AEs), and laboratory tests (excluding lipase) of the prior group (up to 48 hours post-dose for cohort 1, and up to Day 7 post-dose for cohorts 2 - 5).
A minimum of 20-hour interval from the first TY014 treatment subject dosing must take place before the second TY014 treatment subject can be dosed within each cohort. No such time interval will be required for dosing of subsequent TY014 treatment subjects (third subject onwards) within the same cohort, as well as Placebo dosing in dose cohort 1 (i.e. all five placebos can be dosed at the same time).
After 72 hours, subjects will be discharged from trial site and to return for scheduled follow-up visits.
Subjects will be followed for up to approximately Day 84 for PK sampling, with serum samples taken at specified times.
Dose escalations for the Safety (1A) Arm will be guided by a safety review of clinical signs, adverse events (AEs), and laboratory tests (excluding lipase) of the prior dose cohort (up to Day 7).
Similar safety review (up to Day 7) will also be completed for the equivalent dose in Safety Arm (1A) prior to the commencement of the Efficacy Arm (1B) for each specified dose.
Efficacy Arm (1B):
Efficacy Arm is a phase 1B Sequential Time Lagged, Parallel-Group, Randomised, Placebo-Controlled, Double-Blind, Single Ascending Dose Study of TY014 in YF-17D Vaccine Strain-Challenged Healthy Adult Volunteers.
Safety, tolerability and time to achieve aviremia through negative YFV isolation from blood in YF-17D Vaccine Strain-challenged healthy adult volunteers when given an IV infusion of TY014 will be assessed.
Eligible subjects will be randomised into TY014 or Placebo Group in each cohort.
The dose escalation will include up to 40 healthy volunteers in up to four (4) dose cohorts:
- 2 mg/kg, N = 5 TY014 + 5 Placebos
- 5 mg/kg, N = 5 TY014 + 5 Placebos
- 10 mg/kg, N = 5 TY014 + 5 Placebos
- 20 mg/kg, N = 5 TY014 + 5 Placebos Efficacy Arm (1B) will be based on an adaptive trial design, with ten (10) YF-17D vaccinated subjects from each dose cohort being randomised 1:1 into either TY014 or Placebo group, five (5) subjects in each group. After TY014 or placebo administration, safety and efficacy of TY014 in YF-17D Vaccine Strain-Challenged subjects will be assessed.
- If current dose of TY014 shows safety but not efficacy*, Efficacy Arm (1B) will escalate to the next dose cohort. ii) If current dose of TY014 is safe and efficacious*, efficacious dose of TY014 is established and the Efficacy Arm (1B) of the trial is completed.
*Efficacy of TY014 is defined as aviremia by virus isolation being observed in 100% of vaccinated subjects within 48 hours post-dosing.
Subjects will be required to be inpatient at the trial site for approximately 96 hours.
Subjects will be vaccinated with the YF-17D Vaccine on Day -1. On Day 0, 24 hours after vaccination, subjects will then be administered TY014 or Placebo.
A minimum of 20-hour interval from the first two (2) subjects dosing (1 treatment and 1 placebo concurrently) must take place before the third subject can be dosed within each cohort. No such time interval will be required for dosing of subsequent subjects (fourth subject onwards) within the same cohort.
After 96 hours, subjects will be discharged from trial site and are to return for scheduled follow-up visits.
PD and PK measurements will be conducted at various time points throughout the study. Subjects will be followed for up to approximately Day 84 post-dose. Samples for PD (serum and urine) and PK (serum) assessments will be taken at specified time points.
Dose escalations for the Efficacy (1B) Arm will be guided by a safety review of clinical signs, adverse events (AEs), laboratory tests (excluding lipase) and presence of viremia (via virus isolation) of the prior dose cohort (up to Day 14). Escalation to the next dose cohort (e.g. from dose cohort 1 (2 mg/kg) to dose cohort 2 (5 mg/kg), from dose cohort 2 (5 mg/kg) to dose cohort 3 (10 mg/kg) and from dose cohort 3 (10 mg/kg) to dose cohort 4 (20 mg/kg)) will only be conducted if from prior dose cohort (e.g. dose cohort 1 (2 mg/kg), dose cohort 2 (5 mg/kg) and dose cohort 3 (10 mg/kg) respectively):
- safety (up to Day 14 post-dose) has been established through a safety review, and
- presence of viremia (up to 48 hours post-dose) via virus isolation in any of the TY014-treated subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Safety Arm - 0.5 mg/kg | Experimental | Biological: TY014Subject will be administered with 0.5 mg/kg of TY014 via IV infusion over a period of 30 minutes. |
| Safety Arm - Placebo | Placebo comparator | Other: 0.9% SalineSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes. |
| Safety Arm - 2 mg/kg | Experimental | Biological: TY014Subject will be administered with 2 mg/kg of TY014 via IV infusion over a period of 30 minutes. |
| Safety Arm - 5 mg/kg | Experimental | Biological: TY014Subject will be administered with 5 mg/kg of TY014 via IV infusion over a period of 30 minutes. |
| Safety Arm - 10 mg/kg | Experimental | Biological: TY014Subject will be administered with 10 mg/kg of TY014 via IV infusion over a period of 30 minutes. |
| Safety Arm - 20 mg/kg | Experimental | Biological: TY014Subject will be administered with 20 mg/kg of TY014 via IV infusion over a period of 30 minutes. |
| Efficacy Arm - 2 mg/kg | Experimental | Biological: TY014Subject will be administered with 2 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 2 mg/kg Placebo | Placebo comparator | Other: 0.9% SalineSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 5 mg/kg | Experimental | Biological: TY014Subject will be administered with 5 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 5 mg/kg Placebo | Placebo comparator | Other: 0.9% SalineSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 10 mg/kg | Experimental | Biological: TY014Subject will be administered with 10 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 10 mg/kg Placebo | Placebo comparator | Other: 0.9% SalineSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 20 mg/kg | Experimental | Biological: TY014Subject will be administered with 20 mg/kg of TY014 via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
| Efficacy Arm - 20 mg/kg Placebo | Placebo comparator | Other: 0.9% SalineSubject will be administered with 0.9% saline via IV infusion over a period of 30 minutes 24 hours post-YF vaccination. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy adult volunteers, aged 21 to 50 years old, men or women
- Subjects negative for human immunodeficiency virus (HIV), Hepatitis B virus surface Antigen (HBsAg) and Hepatitis C virus (HCV)
- Subjects who have not been vaccinated against or had prior exposure to Yellow Fever Virus (YFV)
- Subjects who have no history of travels to Central America, South America, Africa or any other YF endemic countries, and have no plans to visit Central America, South America, Africa or any other YF endemic countries in the next six (6) months
- Subjects who are willing to comply with the requirements of the study protocol, attend scheduled visits and make themselves available for the duration of the study with access to a consistent means of telephone contact, which may be, but not limited to, at home or at work via landline or mobile
Key exclusion criteria (17 listed)
- Presence of acute infection in the preceding 14 days, or presence of a temperature ≥ 38.0 ˚C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of admission
- History of severe drug and / or food allergies and / or known allergies to the trial product or its components
- Female subject who is pregnant or breast-feeding
- 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
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 |
|---|---|---|
| TY014TY014 Injection, (100 mg/5 mL/Vial), Yellow Fever Virus (YFV) Monoclonal Antibody (mAb) | Biological | Efficacy Arm - 10 mg/kg, Efficacy Arm - 2 mg/kg, Efficacy Arm - 20 mg/kg, Efficacy Arm - 5 mg/kg, Safety Arm - 0.5 mg/kg, Safety Arm - 10 mg/kg, Safety Arm - 2 mg/kg, Safety Arm - 20 mg/kg, Safety Arm - 5 mg/kg |
| 0.9% SalinePlacebo | Other | Efficacy Arm - 10 mg/kg Placebo, Efficacy Arm - 2 mg/kg Placebo, Efficacy Arm - 20 mg/kg Placebo, Efficacy Arm - 5 mg/kg Placebo, Safety Arm - 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.
Percentage Aviremia Post Treatment (Efficacy Arm only)
Time frame: 14 Days
Percentage of YF-17D Vaccine Strain-challenged healthy adult volunteers showing aviremia via virus isolation within 48 hours after given an IV infusion of TY014
8 secondary outcomes
Maximum Concentration (Cmax) - Pharmacokinetic Assessment
Time frame: 84 Days
Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment
Time frame: 84 Days
Area Under the Curve Extrapolated to Infinity (AUC0-∞) - Pharmacokinetic Assessment
Time frame: 84 Days
AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment
Time frame: 84 Days
Half-Life (t1/2) - Pharmacokinetic Assessment
Time frame: 84 Days
Volume of Distribution (Vd) - Pharmacokinetic Assessment
Time frame: 84 Days
Clearance [CL] - Pharmacokinetic Assessment
Time frame: 84 Days
Viral Load Reduction (Efficacy Arm only)
Time frame: 84 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2019.
- Derived from this study: PubMed 32726531Low JG, Ng JHJ, Ong EZ, Kalimuddin S, Wijaya L, Chan YFZ, Ng DHL, Tan HC, Baglody A, Chionh YH, Lee DCP, Budigi Y, Sasisekharan R, Ooi EE. Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody. N Engl J Med. 2020 Jul 30;383(5):452-459. doi: 10.1056/NEJMoa2000226.
- 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 TY014 and 0.9% Saline in people with Treatment of Acute Yellow Fever Virus Infection, run by Tysana 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 11 inclusion and 17 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: finished, as of the sponsor's last update on 25 Oct 2019. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03776786, which also lists 1 linked publication.
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 25 Oct 2019; AzTrials last refreshed its copy on 8 Nov 2026.