A Phase 3/3b, Randomized, Observer-blind, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of Fluad and Fluad Quadrivalent Compared to a Non-adjuvanted Influenza Vaccine in Adults ≥65 Years of Age

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seqirus UK Limited

Participant type

Healthy volunteers

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

20 Oct 2023 → ongoing

Decision date (initial)

2023-09-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Seqirus UK Limited, United Kingdom

External identifiers

EU CT number

2022-503004-24-00

ClinicalTrials.gov

NCT06087640

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Prophylaxis

To demonstrate the efficacy of Fluad in the prevention of RT-PCR-confirmed influenza A and/or B disease due to any influenza strain is non-inferior to that of a non-adjuvanted trivalent influenza vaccine comparator in adults ≥65 years of age.

Secondary objectives 8

1. 3. To evaluate efficacy of MF59-adjuvanted influenza vaccine in the prevention of influenza A and/or B disease due to influenza strains antigenically matched to the strains selected for the seasonal vaccine when compared to non-adjuvanted influenza vaccine, using the protocol-defined ILI definition.
2. 4. To evaluate efficacy of MF59-adjuvanted influenza vaccine in the prevention of culture-confirmed influenza A and/or B disease due to any strain regardless of antigenic match to the strains selected for the seasonal vaccine when compared to non-adjuvanted influenza vaccine, using the protocol-defined ILI definition.
3. 5. To evaluate efficacy of MF59-adjuvanted influenza vaccine in the prevention of RT-PCR-confirmed influenza A and/or B disease due to any influenza strain when compared to non-adjuvanted influenza vaccine, using the modified Centers for Disease Control and Prevention (CDC) ILI definition as well as the World Health Organization (WHO) ILI definition.
4. 6. To evaluate efficacy of MF59-adjuvanted influenza vaccine in the prevention of influenza A and/or B disease due to influenza strains antigenically unmatched to the strains selected for the seasonal vaccine when compared to non-adjuvanted influenza vaccine, using the protocol-defined ILI definition.
5. To evaluate the immunogenicity of MF59-adjuvanted influenza vaccine as compared to non-adjuvanted influenza vaccine measured by HI assay against homologous vaccine strains before and 21 days after vaccination in a subset of subjects within each influenza season.
6. To evaluate the safety of MF59-adjuvanted influenza vaccine as compared to non-adjuvanted influenza vaccine determined by occurrence of all adverse events (AEs) reported within 30 minutes after the study vaccination and serious adverse events (SAEs), AEs leading to early study withdrawal, and adverse events of special interest (AESIs) during the entire study period.
7. Key Secondary Efficacy Objective: 1. To demonstrate the efficacy of MF59-adjuvanted influenza vaccine, regardless of valency, in the prevention of RT-PCR-confirmed influenza A and/or B disease due to any influenza strain is non-inferior to that of a non-adjuvanted influenza vaccine comparator in adults ≥65 years of age.
8. Key Secondary Efficacy Objective: 2. To demonstrate the efficacy of Fluad Quadrivalent in the prevention of RT-PCR-confirmed influenza A and/or B disease due to any influenza strain is non-inferior to that of a non-adjuvanted quadrivalent influenza vaccine comparator in adults ≥65 years of age.

Conditions and MedDRA coding

Influenza virus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1. Adults of ≥65 years of age on the day of vaccination.
2. 2. Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. 3. Individuals who have the ability to comply with study procedures including follow-up.

Exclusion criteria 12

1. 1. Bedridden subjects (i.e. confined to bed by sickness or old age).
2. 10. Acute (severe) febrile illness.
3. 11. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
4. 12. Study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel.
5. 2. Subjects that are incapacitated and because of that in need of a Legally Authorized Representative.
6. 3. Receipt of any influenza vaccine within 6 months prior to enrollment or any plan to receive influenza vaccine while participating in the study.
7. 4. Hypersensitivity, including allergy, to any component of vaccines whose use is foreseen in this study, or severe allergic reaction (e.g. anaphylaxis) to previous influenza vaccination.
8. 5. Known history of Guillain-Barré syndrome or another demyelinating disease such as encephalomyelitis and transverse myelitis.
9. 6. Clinical conditions representing a contra-indication to intramuscular administration of vaccines or blood draw.
10. 7. Abnormal function of the immune system resulting from: a. Clinical conditions; b. Systemic administration of corticosteroids (PO/IV/IM)8 at a dose ≥20 mg/day of prednisone (or equivalent) for more than 14 consecutive days within 90 days prior to informed consent; Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted; c. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent;
11. 8. Receipt of immunoglobulins or any blood products within 180 days prior to informed consent;
12. 9. Receipt of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the study vaccination, or planned use during the entire study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), occurring from 14 days after vaccination (ie study day 15) and until the end of influenza season, using the protocol-defined ILI definition.

Secondary endpoints 7

1. First-occurrence of culture-confirmed influenza, due to influenza Type A and/or B virus antigenically matched to the vaccine strains selected for the seasonal vaccine, occurring from 14 days after vaccination (ie study day 15) and until the end of influenza season, using the protocol-defined ILI definition.
2. First-occurrence of culture-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), occurring from 14 days after vaccination and until the end of influenza season, using the protocol-defined ILI definition.
3. First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), occurring from 14 days after vaccination (ie study day 15) and until the end of influenza season, using the modified CDC ILI definition as well as the WHO ILI definition.
4. First-occurrence of culture-confirmed influenza, due to influenza Type A and/or B virus antigenically unmatched to the vaccine strains selected for the seasonal vaccine, occurring from 14 days after vaccination (ie study day 15) and until the end of influenza season, using the protocol-defined ILI definition
5. The measures for immunogenicity as determined by the serum HI antibody titers for Day 1 and Day 22 for four vaccine homologous influenza strains are as follows for the subjects selected for the immunogenicity subset in each season – reference is made to the study protocol, page 80..
6. Safety of the study vaccines will be assessed in all subjects in terms of the frequency of reported AEs including: • All AEs reported within 30 minutes after vaccination; • SAEs reported during the entire study period; • AESIs reported during the entire study period; • AEs leading to premature withdrawal from the study during the entire study period.
7. Key Secondary Efficacy Endpoint: First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), occurring from 14 days after vaccination (ie study day 15) and until the end of influenza season, using the protocol-defined ILI definition.

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seqirus UK Limited

Sponsor organisation

Seqirus UK Limited

Address

The Point, 29 Market Street 29 Market Street

City

Maidenhead

Postcode

SL6 8AA

Country

United Kingdom

Scientific contact point

Organisation

Seqirus UK Limited

Contact name

Seqirus UK Limited Clinical Trial Disclosures

Public contact point

Organisation

Seqirus UK Limited

Contact name

Seqirus UK Limited Clinical Trial Disclosures

Third parties 6

Locations

10 EU/EEA countries · 72 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 161 files

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

Application history

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