VAXXAIR TRIAL: In-depth Immunological Analysis of Airway Immunity following Nasal Live Attenuated and Intramuscular Influenza Vaccine A randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gentofte Hospital

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

23 Dec 2024 → ongoing

Decision date (initial)

2024-01-16

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk Foundation

External identifiers

EU CT number

2023-506166-31-01

ClinicalTrials.gov

NCT05921448

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To understand and determine immunological and airway epithelial factors for whether a nasally administered LAIV vaccination is effective in establishing immunity towards specific H/N influenza subtypes compared to quadrivalent IIV.

Secondary objectives 4

1. 1) Intranasally administered quadrivalent LAIV influenza vaccine will produce a stronger mucosal cellular immune response* at day 7 as compared with intramuscular administered quadrivalent influenza vaccine in a. Lower respiratory tract b. Upper respiratory tract
2. 2) Intranasally administered quadrivalent LAIV influenza vaccine will produce a stronger mucosal humoral immune response** at day 7 (as compared with intramuscular administered quadrivalent influenza vaccine) in a. Lower respiratory tract b. Upper respiratory tract
3. 3) Intranasally administered quadrivalent LAIV influenza vaccine will produce a stronger mucosal cellular immune response* at day 28 as compared with intramuscular administered quadrivalent influenza vaccine in a. Lower respiratory tract b. Upper respiratory tract
4. 4) Intranasally administered quadrivalent LAIV influenza vaccine will produce a stronger mucosal humoral immune response** at day 28 as compared with intramuscular administered quadrivalent influenza vaccine in a. Lower respiratory tract b. Upper respiratory tract *Defined as at least double (2 x) fraction of antigen activated CD4+ T-lymphocytes **Defined as at least (4 x) HAI-specific IgA “Lower respiratory tract” is here considered: Middle lobe (right lung) or Lingula (Left lung) “Upper respiratory tract” is here defined as in the nasal cavity 3-5 cm from apex nasi

Conditions and MedDRA coding

Influenza

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Age ≥ 20-40 years
2. Participants who have not received any influenza as per medical history and documented in DDV (electronic vaccine registry)

Exclusion criteria 18

1. Laboratory-confirmed influenza infection during the past year documented by a positive PCR test in the Danish Microbiological database
2. Total IgG levels < 6.1 g/L obtaining at screening visit
3. Influenza specific IgA in upper quartile in mucosa. Upper quartile will be defined “real time” in the screening population
4. Active smoker
5. BMI >35
6. Charlson (score > 0)
7. Women of childbearing potential not using safe contraception, or who are pregnant, or breast-feeding
8. Any allergies to components of or contraindication for Vaxigriptetra® or Flumist®
9. Participants who have experienced severe adverse reactions to previous influenza vaccinations or components of the vaccines, including allergy to egg
10. Use of immunosuppressive drugs within the past 6 months or who are currently using them
11. Known immunodeficiency disorders [any diagnosis that would qualify to an ICD-10 diagnosis in the categories DD80-DD89 (except DD86)
12. HIV, HBV, HCV laboatory confirm active infection at screening visit
13. Have an acute illness, including an oral temperature ≥ 38°C, within 3 days prior to vaccination
14. Have received any vaccines, including live-attenuated vaccines within 4 weeks before inclusion, or plan receipt of such vaccines within 30 days following the inclusion
15. Any known malignant neoplasm within 5 years (except basal carcinoma of the skin)
16. Severe mental illness or linguistic issues which significantly impedes cooperation
17. Inability to provide written informed consent
18. Previous medical history, evidence of an intercurrent illness or any condition that, in the opinion of the investigator, would interfere with evaluation of the study vaccine products or interpretation of subject safety or that may compromise the safety of the subject in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Cellular: Antigen activated CD4+ T-lymphocytes measured at –14, day +7 day +28 [+/-5 days]and day +90 [+/-5 days] after vaccination.
2. Humoral: Number of participants with ≥-4-fold rise in mucosal antibody titer against each vaccine virus haemagglutinin antigens vaccine-specific antibody (IgG and IgA) titers in respiratory secretions measured using antibody titer measured at –14, day +7 day +28 [+/-5 days]and day +90 [+/-5 days] after vaccination

Secondary endpoints 2

1. Cellular: Quantification and characterization of leukocyte cell subsets, incl T- and B-cell subsets and activation patterns, using highly standardized flowcytometry in combination with single cell RNAsequencing (scRNAseq) analysis coupled with single cell surface marker profiling (CITEseq or similar platform) for in-depth characterization of immune cell subsets measured at –14, day +7 day +28 [+/-5 days]and day +90 [+/-5 days] after vaccination
2. Humoral: Number of participants with ≥-4-fold rise in serum antibody titers against each vaccine virus haemagglutinin antigens vaccine-specific antibody (IgG) titers in serum measured using antibody titer measured measured at –14, day +7 day +28 [+/-5 days]and day +90 [+/-5 days] after vaccination.

Investigational products

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

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gentofte Hospital

Sponsor organisation

Gentofte Hospital

Address

Kildegaardsvej 28

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Gentofte Hospital

Contact name

Jens-Ulrik Stæhr Jensen

Public contact point

Organisation

Gentofte Hospital

Contact name

Jens-Ulrik Stæhr Jensen

Third parties 1

Sponsor responsibilities

Article 77 compliance

Gentofte Hospital

Contact point sponsor

Gentofte Hospital

Article 77 implementation

Gentofte Hospital

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 19 files

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

Application history

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