Phase III Randomized, Observer-Blind Study on Safety and Immunogenicity of High-Dose Trivalent Influenza Vaccine in Adults Aged 60 and Above
- Trial ID
- 2024-519743-15-00
- Protocol
- INFQ-324-0476
- Sponsor
- Abbott Biologicals B.V.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **noninferiority** of Abbott's candidate trivalent high-dose (TIV-HD) influenza vaccine in adults aged 60 years and older. This will be assessed by comparing the postvaccination hemagglutination-inhibition (HI) antibody titers with those of Efluelda® 28 days after the first vaccination. Establishing noninferiority is clinically relevant as it may provide an alternative vaccination option for older adults, potentially enhancing influenza immunization strategies in this population.
Secondary objectives include:
- Describing the induced **humoral immunogenicity** for each vaccination group after the first vaccination and revaccination, measured by the HI and virus neutralization (VN) assays.
- Describing the induced **cell-mediated immunity (CMI)** for each vaccination group after the first vaccination and revaccination.
- Comparing the induced humoral and CMI immunogenicity after revaccination with that after the first vaccination for each group.
- Comparing the **reactogenicity** and safety of the TIV-HD vaccine with Efluelda® and Influvac®.
Participants
The clinical trial focuses on **influenza immunisation** and involves a study population of adults aged 60 years and older. Both male and female participants are included, provided they are overall healthy based on the clinical judgment of the investigator, which includes a review of medical history and clinical assessments. Participants may have underlying illnesses if their symptoms are controlled, and any prescribed medication must have been stable for at least three months prior to the study. Female participants must be postmenopausal. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to comply with study requirements, including the use of a personal or provisioned device to record solicited events and other protocol-required data.
Plans and Procedures
The clinical trial is designed as a **randomized**, observer-blind, active-controlled, Phase III study aimed at assessing the safety and immunogenicity of a high-dose influenza vaccine in adults aged 60 years and older. The primary objective is to demonstrate the noninferiority of the candidate trivalent high-dose vaccine compared to Efluelda® in terms of postvaccination hemagglutination-inhibition (HI) antibody titers 28 days after the first vaccination. The trial is expected to commence recruitment on September 8, 2025, and conclude by November 30, 2026, with an estimated duration of approximately 14 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, health status, and ability to comply with study requirements. The inclusion criteria specify that participants must be adults aged 60 years or older, in good health as determined by the investigator, and able to provide informed consent. Female participants must be postmenopausal. Following the screening, eligible participants will receive the first vaccination, with follow-up visits scheduled to monitor safety and immunogenicity outcomes. The primary endpoint will be evaluated 28 days post-vaccination, with additional follow-up visits to assess secondary endpoints, including postvaccination HI and virus neutralization (VN) geometric mean titers (GMTs), seroconversion rates, and adverse events.
The expected length of participant involvement is up to 6 months post-vaccination, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or adverse events that warrant discontinuation as determined by the investigator. The study will employ a double-blind methodology to ensure unbiased assessment of outcomes, with both participants and investigators blinded to the treatment allocation. The trial will utilize a structured protocol to ensure the collection of comprehensive data on the safety and immunogenicity of the high-dose influenza vaccine, contributing valuable insights into its potential use in the target population.
Treatment
The clinical trial involves the administration of three different **influenza vaccines**. The first experimental medication is the **Trivalent Influenza Vaccine - High Dose (TIV-HD)**, which is a suspension for injection in a pre-filled syringe. This vaccine contains the active substances **Influenza Virus A/Darwin/9/2021 SAN-010 (H3N2)**, **Influenza Virus B/Austria/1359417/2021-like strain (B/Austria/1359417/2021, BVR-26)**, and **A/Victoria/4897/2022 (H1N1)pdm09-like strain (A/Victoria/4897/2022, IVR-238)**. The vaccine is administered via subcutaneous injection, with a maximum daily and total dose of 180 micrograms. The treatment period is limited to one day.
The second treatment used in the study is **Efluelda**, a trivalent influenza split vaccine (inactivated) provided as a suspension for injection in a pre-filled syringe. This vaccine includes the active substances **Influenza Virus A/Darwin/9/2021 SAN-010 (H3N2)**, **Influenza Virus B/Michigan/01/2021**, and **Influenza A/Victoria/4897/2022 IVR-238 (H1N1), inactivated**. Efluelda is administered intramuscularly, with a maximum daily and total dose of 180 micrograms, and the treatment period is also one day.
The third treatment is **Influvac**, a suspension for injection containing the active substances **Influenza Virus B/Austria/1359417/2021-like strain (B/Austria/1359417/2021, BVR-26)**, **A/Victoria/4897/2022 (H1N1)pdm09-like strain (A/Victoria/4897/2022, IVR-238)**, and **Influenza A Virus/Thailand/8/2022 (H3N2)-like strain (A/California/122/2022, SAN-022), inactivated**. This vaccine is also administered via intramuscular injection, with a maximum daily and total dose of 45 micrograms, and a treatment period of one day.
All vaccines are structurally diverse substances classified as vaccines, and none of them are pediatric formulations. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The trial aims to assess the safety and immunogenicity of the high-dose influenza vaccine in adults aged 60 years and older, comparing it to the standard-dose vaccines.
Efficacy
The efficacy of the high-dose trivalent influenza vaccine (TIV-HD) in adults aged 60 years and older will be assessed by comparing the postvaccination **hemagglutination-inhibition (HI) antibody titers** with those of the Efluelda® vaccine. The primary endpoint for evaluating efficacy is the postvaccination HI geometric mean titers (GMTs) for each of the three influenza strains, measured 28 days after the first vaccination. Secondary endpoints include postvaccination HI GMTs after revaccination, postvaccination virus neutralization (VN) GMTs after both the first and revaccination, and postvaccination HI and VN geometric mean fold increases (GMFIs) and seroconversion rates.
Additional secondary endpoints involve the analysis of postvaccination reverse cumulative distribution (RCD) curves for HI and VN titers, postvaccination cell-mediated immunity (CMI) values, and the occurrence of unsolicited adverse events (AEs) within 28 days following each vaccination. Serious adverse events (SAEs), adverse events of special interest (AESIs), medically attended events (MAEs), and new chronic illnesses (NCIs) will be monitored from Day 29 to Month 6 postvaccination. Solicited injection site and systemic adverse reactions will be recorded within 7 days following each vaccination, with specific attention to reactions such as erythema, swelling, induration, pain, ecchymosis, fever, headache, fatigue, malaise, myalgia, arthralgia, sweating, and shivering.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Willing and able to give informed consent and able to adhere to all protocol-required study procedures.
- Adults ≥ 60 years of age who are overall healthy in the clinical judgment of the investigator based on the medical history and clinical assessment (including physical examination, vital signs, clinical laboratory tests). Subjects may have underlying illnesses as long as their symptoms/signs are controlled. If on regular prescribed medication for a condition, the medication dose must have been stable for at least 3 months preceding study vaccination.
- Female subjects must be postmenopausal, defined as female subjects with at least 1 year of absence of menstruation or follicle-stimulating hormone and luteinizing hormone values of ovarian suppression.
- Ability to comply with study requirements, including the use of an application on a personal device (i.e., smartphone, tablet, etc.) or a provisioned device to record solicited events and other per-protocol required data.
Exclusion Criteria
- History of allergy to egg or chicken proteins, or history of any reaction or hypersensitivity to a previous dose of influenza vaccine components.
- Chronic systemic administration (defined as more than 14 days) of immunosuppressant or immune-modifying medication (such as monoclonal antibodies) for five elimination half-lives or the proposed time in Appendix 16.5, whichever is longer, prior to the first study vaccination or planned use thereof during the study.
- Receipt of blood or blood products within 3 months preceding enrollment.
- Being a solid organ or bone marrow/stem cell transplant recipient.
- Use of cytotoxic drugs, anticancer chemotherapy, or radiation therapy within 36 months before the day of study vaccination.
- Receipt of another investigational agent within 30 days prior to study vaccination, or planned use during the entire study period.
- Known drug or alcohol abuse.
- Planned surgery requiring a general anesthetic, or planned surgery requiring inpatient hospitalization for at least 24 hours during the entire study period.
- Being an employee of the Sponsor/CRO conducting this study, personnel of the study site or placed in an institution by regulatory or legal ordinance.
- Any concurrent condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with the evaluation of the study vaccine including (but not limited to) bleeding disorder, immunodeficiency, seizure disorder, or acute or progressive hepatic, renal, neurological, neuromuscular, or psychiatric disease.
- Any other reason that, in the investigator’s opinion, prohibits the inclusion of the subject into the study.
- History of serious adverse reaction to any influenza vaccine.
- History of Guillain-Barré syndrome.
- Laboratory confirmed influenza infection or vaccination against influenza in the 6 months preceding enrollment.
- Receipt of any vaccine within the preceding 4 weeks of study vaccination or planned vaccination within the 4-week period following each study vaccination.
- Having fever and/or acute disease or infection on the day of the first study vaccination (enrollment can be deferred for up to 2 weeks, provided the subject remains otherwise eligible). - Fever is defined as body temperature ≥ 38.0°C (measured by oral method). - Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
- Immunocompromising condition or immunosuppressive therapy within 6 months preceding enrollment.
- Thrombocytopenia or bleeding disorder contraindicating intramuscular vaccination.
- Chronic use of systemic corticosteroids at a dose ≥ 20 mg/day of prednisone or equivalent for 14 consecutive days or more, prior to the first study vaccination or planned use thereof during the study. Topical use of corticosteroids (e.g., cream, ocular drops, inhalation and intranasal sprays), within the dosage noted on the product label, is allowed.
- Planned administration of any influenza vaccine (other than the study vaccine) for the entire study period.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 08 Sept 2025 | 180 |
 Bulgaria | Not Recruiting | 08 Sept 2025 | 364 |
 Estonia | Not Recruiting | 08 Sept 2025 | 240 |
 Finland | Not Recruiting | 08 Sept 2025 | 276 |
 Spain | Not Recruiting | 08 Sept 2025 | 133 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Influvac, suspensie voor injectie 0,5 ml (influenza vaccin, oppervlakte antigeen, geïnactiveerd). | Comparator | SUSPENSIE VOOR INJECTIE | INTRAMUSCULAR INJECTION | 45 | 1 | PRD439869 |
Efluelda Injektionssuspension in einer Fertigspritze
Trivalenter Influenza-Spaltimpfstoff (inaktiviert), 60 Mikrogramm HA/Stamm | Comparator | INJEKTIONSSUSPENSION IN EINER FERTIGSPRITZE | INTRAMUSCULAR INJECTION | 180 | 1 | PRD11770791 |
Trivalent Influenza Vaccine - High DoseTIV-HD | Test | SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 180 | 1 | PRD12063666 |