An Experimental Medicine Decipher of a Minimum Correlate of Cellular Immunity

NCT05568953 | Unknown Phase 2

• 1 other identifier: JEYF-Tcell-001
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

We hypothesize that a high CD4+ and CD8+ T cell count will reduce viremia upon challenge with a structurally heterologous virus, and correspondingly result in reduced magnitude of host response to challenge infection. Primary Objective: To compare, after challenge with a structurally heterologous vaccine, the differences in levels of viremia between healthy adults who received primary vaccination with either YF17D vaccine, chimeric JE-YF17D vaccine, or inactivated JE vaccine. 58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Subjects in Arm B1 will receive JE-YF17D vaccine (Imojev, Sanofi Pasteur) on Day 0 followed by YF17D vaccine (Stamaril, Sanofi Pasteur) on Day 28. Subjects in Arm B2 will receive Stamaril on Day 0 followed by Imojev on Day 28. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Subjects in Arm B3 will receive inactivated JE vaccine (Ixiaro, Valneva) on Day 0 followed by Stamaril on Day 28. The rationale for these three study arms is as follows: Arm B1 will show the impact low levels of viremia, and the resultant low levels of virus-specific CD4+ and CD8+ T cells, would have on YF17D infection. In contrast, YF17D vaccination in Arm B2 would produce high levels of viremia, and in turn high levels virus-specific T cells, thus likely ameliorating JE-YF17D infection. Arm B3 will serve as the control arm, as vaccination with inactivated JE vaccine would not produce any YF17D-specific T cell response. Notably, the first vaccination in Arms B1 and B2 would also provide the viremia response in the absence of virus-specific T cells, which would serve as a reference point to interpret the outcome of the second vaccination.

Conditions

Infectious Disease; Yellow Fever; Japanese Encephalitis; Viral Infection

Keywords

Yellow Fever; Japanese Encephalitis; YF17D; JE-YF17D; T-cell Immunity; Cellular Immunity; Live-attenuated Vaccines

Outcome Measures

Primary Outcomes (1)

• Viremia levels after second vaccination

  Viremia level (genome copies/ml) after second vaccination with either JE-YF17D or YF17D

  Day 0 to Day 58

Secondary Outcomes (5)

• T cell responses after vaccination

  Day 0 to Day 58

• Viremia level after first vaccination

  Day 0 to Day 58

• Duration of viremia after second vaccination

  Day 0 to Day 58

• Antibody Titres

  Day 0 to Day 58

• Rates of Adverse Events

  Day 0 to Day 58

Other Outcomes (2)

• Innate Immune Gene Expression

  Day 0 to Day 58

• Cytokine levels

  Day 0 to 58

Study Arms (3)

Arm 1 (JE-YF17D vaccine followed by YF17D vaccine)

EXPERIMENTAL

28 subjects will receive one dose of the JE-YF17D vaccine (Imojev, Sanofi Pasteur, 0.5mls (4.0 - 5.8 log plaque forming units \[PFU\])) on Day 0 followed by one dose of the YF17D vaccine (Stamaril, Sanofi Pasteur, 0.5mls (3 - 4 log PFU) ) on Day 28.

Biological: Stamaril; Biological: Imojev

Arm 2 (YF17D vaccine followed by JE-YF17D vaccine)

EXPERIMENTAL

28 subjects will receive one dose of the YF17D vaccine (Stamaril, Sanofi Pasteur, 0.5mls (3 - 4 log PFU)) on Day 0 followed by one dose of the JE-YF17D vaccine (Imojev, Sanofi Pasteur, 0.5mls (4.0 - 5.8 log plaque forming units \[PFU\]) on Day 28.

Biological: Stamaril; Biological: Imojev

Arm 3 (Inactivated JE vaccine followed by YF17D vaccine)

EXPERIMENTAL

14 subjects will receive one dose of the inactivated JE vaccine (Ixiaro, Valneva, 0.5mls) on Day 0 followed by one dose of the YF17D vaccine (Stamaril, Sanofi Pasteur, 0.5mls (3 - 4 log PFU)) on Day 28.

Biological: Stamaril; Biological: Ixiaro

Interventions

Stamaril BIOLOGICAL

Stamaril is licensed by the Health Sciences Authority (HSA), Singapore. The vaccine are manufactured by Sanofi Pasteur and sourced from Sanofi Pasteur's local distributor.

Also known as: YF17D vaccine

Arm 1 (JE-YF17D vaccine followed by YF17D vaccine); Arm 2 (YF17D vaccine followed by JE-YF17D vaccine); Arm 3 (Inactivated JE vaccine followed by YF17D vaccine)

Imojev BIOLOGICAL

Imojev is licensed by the Health Sciences Authority (HSA), Singapore. The vaccine are manufactured by Sanofi Pasteur and sourced from Sanofi Pasteur's local distributor.

Also known as: JE-YF17D vaccine

Arm 1 (JE-YF17D vaccine followed by YF17D vaccine); Arm 2 (YF17D vaccine followed by JE-YF17D vaccine)

Ixiaro BIOLOGICAL

Ixiaro is licensed by the Health Sciences Authority (HSA), Singapore. The Ixiaro vaccines are manufactured by Valneva and sourced from local distributor, Aenon Pharmaceuticals SEA Pte Ltd.

Also known as: Inactivated Japanese Encephalitis vaccine

Arm 3 (Inactivated JE vaccine followed by YF17D vaccine)

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults, 21-45 years of age at time of screening
• Willing to comply to study procedures and adhere to study schedule visits.
• Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.
• Accessible vein for blood collection.
• Ability to provide informed consent.
• Female subjects of non-child bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post-menopausal subjects must have had at least 12 months of natural (spontaneous) amenorrhea
• Female subjects of child bearing potential with negative urine pregnancy tests on the day of screening and vaccination.
• 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) or practice abstinence for 10 days after vaccination.

You may not qualify if:

• History of presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, haematological, endocrine or immunosuppressive disorders that would be a risk factor when administered the investigational product (IP)
• Previous receipt of Imojev, Stamaril or Ixiaro vaccines, or any other yellow fever or Japanese encephalitis vaccines
• Previous history of Yellow fever virus or Japanese encephalitis infection
• Known allergy to Imojev, Stamaril or Ixiaro vaccines or their components
• History of severe food/drug/vaccine allergies e.g. angioedema, anaphylaxis
• Known allergy to egg or egg products
• History of thymus gland disease
• Diagnosed with cancer or on treatment for cancer (with the exception of localized basal cell carcinoma) within 3 years prior to screening
• Evidence of clinically significant anemia (Hb \<10 g/dl)
• Blood donation exceeding \>450mls in the past 3 months
• Presence of acute infection in the preceding 7 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 first dose
• Woman who is pregnant or breast feeding
• Evidence of substance abuse, or previous substance abuse including alcohol
• Participation in a study involving administration of an investigational compound (including investigational vaccines) within the past three months, or planned participation during the duration of this study.
• Receipt of anti-inflammatory drugs (such as NSAIDs or systemic steroids) in the past 7 days.

Sponsors & Collaborators

• Singapore General Hospital: lead
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

SingHealth Investigational Medicine Unit

Singapore, Singapore

RECRUITING

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Related Links

• Centers for Disease Control and Prevention. Yellow Fever 2018

MeSH Terms

Conditions

Communicable Diseases; Yellow Fever; Encephalitis, Japanese; Virus Diseases

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Shirin Kalimuddin, MRCP (UK)

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Ying Ng

CONTACT

63237572; ng.jin.ying@singhealth.com.sg

Lavanya Lakshmi Jeeva

CONTACT

63237532; lavanya.lakshmi.jeeva@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Arms B1 and B2 will be double-blinded. Arm B3 will be open label.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Randomization will be performed via a web-based randomization system: http://www.randomization.com by an independent person who has no direct contact with the subjects. Randomization opaque envelopes will be prepared by an independent team in accordance to the Master Randomization List generated. The randomization envelopes are to be opened sequentially for each enrollment by the study team and will determine the subject's allocation to one of the three groups. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Enrolled subjects will be randomised into 1 of 3 arms (Arm B1, Arm B2 and Arm B3) in a 2:2:1 ratio. The study will be double-blinded.

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: October 6, 2022
• Study Start: September 28, 2022
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

SG (1)