A randomized controlled trial to compare the immunogenicity and skin imprinting of intradermal, subcutaneous and intramuscular yellow fever vaccination

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institute Of Tropical Medicine

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

2 Jan 2025 → ongoing

Decision date (initial)

2024-09-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis

To compare the number and proportion of skin-resident memory T cells against YFV (YFV-TRM) after YF vaccination by vaccination route at D28.

Secondary objectives 7

1. To compare the number and proportion of circulating effector- (YFV-TEM) and central-memory T cells against YFV (YFV-TCM) by vaccination route
2. To compare the number/proportion of YFV-TRM, YFV-TEM, YFV-TCM cells by vaccination route, stratified by CD4+ and CD8+ T cell differentiation subsets
3. To compare the YFV neutralizing antibody titre (YFV-nAbs) by vaccination route
4. To compare the dynamics in generation and durability of the vaccine-induced, circulating nAbs (YFV-nAbs) and (poly-functional) YFV-specific T cell responses (YFV-TEM, and YFV-TCM) over time by vaccination route
5. To determine the correlation between the ‘conventional’ YFV-nAb response and the YFV-TEM, YFV-TCM and YFV-TRM responses
6. To describe and report the safety by occurrence of (serious) adverse events by study arm
7. To estimate the association of the level of YFV-(n)Ab, YFV-TEM, YFV-TCM and YFV-TRM responses with local and systemic adverse events after vaccination.

Conditions and MedDRA coding

Yellow fever

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. >/=18 to ≤50 years of age
2. BMI >/=18,5 kg/m2 and ≤35 kg/m2
3. Agreement to refrain from blood donation and other vaccinations 30 days following vaccination
4. Agreement to share and discuss participant’s medical history and medical records when relevant
5. Able and willing to provide written informed consent
6. Willing to use a highly effective method of contraception up to 30 days after study vaccination (in case of women with childbearing potential).

Exclusion criteria 21

1. Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC within 24 hours prior to the planned dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator
2. Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer and HIV/HBV infection); asplenia; recurrent severe infections and use of immunosuppressant medication (including antineoplastic and immunomodulating agents or radiotherapy) within the last 6 months prior to enrolment, except topical or short-term oral steroids (<2 weeks of daily receipt of 20 mg of prednisone or equivalent). Refer to annex 1 for a list of immunosuppressive medication
3. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, psychiatric and neurological illness (mild/moderate well controlled comorbidities are allowed)
4. History of anaphylaxis, allergic disease or reactions to any component of the study vaccine, including eggs or chicken proteins
5. History of acute polyneuropathy (eg, Guillain-Barré syndrome)
6. History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections, SC injections or venipuncture
7. History of thymus dysfunction (including myasthenia gravis, thymoma) or thymectomy
8. Any other significant disease, disorder, planned surgery, or finding which may significantly affect the ability of the volunteer to participate in the study or impair interpretation of the study data
9. Suspected or known alcohol or drug dependency
10. Breastfeeding, pregnancy or planning to become pregnant up to 30 days after the study vaccination
11. Tendency to keloid (scar) formation in response to skin damage
12. Skin diseases or tattoo at the biopsy or vaccination site
13. In the opinion of the investigator, unlikely compliance to the requirements of the study
14. Receipt of any vaccine (licensed or experimental) within 30 days prior to enrolment
15. Active participation in another interventional clinical study with active substance intake or large medical procedures affecting the study procedures during the trial or 1 month prior to enrolment
16. Individuals who are working at the investigational site or within the research team of this study and their close relatives
17. Subjects with a confirmed flavivirus infection in the past
18. Subjects who already received a flavivirus vaccination prior to enrolment or are planning a flavivirus vaccination during the course of the trial other than the study vaccination.
19. Subjects who received immunoglobulins and/or any blood or blood derived products within 3 months preceding study vaccination (or planned administration during the study)
20. Subjects who are currently on anticoagulant therapy
21. Subjects who are continuously using systemic antivirals

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The percentage of YFV-specific T cells within the skin-resident lymphocyte parent population at D28, measured by flow cytometry.
2. The absolute number of YFV-specific T cells within the skin-resident lymphocyte parent population at D28, measured by flow cytometry.

Secondary endpoints 11

1. Percentage and absolute number of circulating and YFV-specific TCM and TEM cells within the CD3+ lymphocyte parent population at D28, and increase in their percentage and absolute number from D0 to D28.
2. Percentage and absolute number of YFV-specific TRM, TCM and TEM CD4+ and CD8+ T cells within the skin-resident or CD3+ lymphocyte parent population at D28.
3. The serum dilutions at which 50% viral neutralization occurs (NT50) as measured by the certified VNT (virus neutralization test) assays at D28, and the increase in their percentage and absolute number from D0 to D28.
4. The nAbs NT50 titres, IFNy+ spot forming units (SFU) and IFNy/TNF-a/IL-2+ SFU at D0, D14, D28 and D120 measured by VNT and ELISpot/fluorospot respectively.
5. At all timepoints, the NT50 of VNT testing and IFNy+ spot forming units (SFU) and IFNy/TNF-a/IL-2+ SFU. In addition at D0 and D28 , the percentage and absolute number of YFV-specific TRM, TCM and TEM cells within the CD3+ lymphocyte parent population.
6. The occurrence of solicited and unsolicited local Adverse Events (AEs) [Up to Day 28 after vaccination]
7. The occurrence of solicited and unsolicited systemic AEs [Up to Day 28 after vaccination]
8. The occurrence of Serious Adverse Events (SAE’s) [Up to D120]
9. The occurrence of solicited and unsolicited local Adverse Events (AEs) [Up to Day 28 after vaccination]
10. The occurrence of solicited and unsolicited systemic AEs [Up to Day 28 after vaccination]
11. The absolute number of YFV-specific TRM, TCM and TEM cells at D28

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institute Of Tropical Medicine

Sponsor organisation

Institute Of Tropical Medicine

Address

Nationalestraat 155

City

Antwerp

Postcode

2000

Country

Belgium

Scientific contact point

Organisation

Institute Of Tropical Medicine

Contact name

Wim Adriaensen

Public contact point

Organisation

Institute Of Tropical Medicine

Contact name

Wim Adriaensen

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications