A phase IV study to investigate the immunogenicity of the Seqirus licensed MF59 adjuvanted zoonotic influenza vaccine (H5N8) in adults previously vaccinated in 2009 with the Matrix M adjuvanted virosomal influenza (H5N1) vaccine compared to H5 naïve adults.
- Trial ID
- 2025-522593-36-00
- Protocol
- SEQVAC1
- Sponsor
- Helse Bergen HF
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the humoral immune response to the Seqirus zoonotic influenza vaccine in participants previously primed with the PanFluVac Matrix M adjuvanted H5N1 influenza vaccine, and in H5N1 vaccine-naïve participants. This objective addresses the clinical relevance of understanding immune memory and cross-protection in populations with prior exposure to avian influenza antigens compared to immunologically naïve individuals, which is critical for pandemic preparedness strategies.
The secondary objectives include:
• To evaluate the humoral immune response to the Seqirus zoonotic influenza vaccine in participants previously primed with the PanFluVac H5N1 influenza vaccine, as well as in H5N1 vaccine-naïve participants
• To evaluate the heterologous humoral immune response to the Seqirus zoonotic influenza vaccine in participants previously primed with the PanFluVac H5N1 influenza vaccine, as well as in H5N1 vaccine-naïve participants
• To evaluate the safety of the Seqirus zoonotic influenza vaccine in participants previously primed with the PanFluVac H5N1 influenza vaccine, as well as in H5N1 vaccine-naïve participants
Participants
The sponsor does not provide information regarding the total number of participants enrolled in this clinical trial. The study population consists of adults aged **35 to 70 years**, with both male and female participants included. The trial encompasses two distinct groups: individuals previously primed with the PanFluVac Matrix M adjuvanted **H5N1 influenza vaccine** during a Phase I study in 2009, and H5N1 vaccine-naive participants. Eligible participants are required to be overtly healthy or medically stable as determined by medical evaluation, with chronic stable conditions such as **hypertension** or cardiac disease permitted if deemed stable by the investigator and unlikely to influence immune response. Participants must have a **Body Mass Index** ranging from 18.0 to 35.0 kg/m². Female participants of childbearing potential must practice adequate contraception from one month prior to study intervention and provide a negative urine pregnancy test, while those of non-childbearing potential, defined by **hysterectomy**, bilateral oophorectomy, bilateral salpingectomy, or **postmenopausal** status, are also eligible. All participants must be capable of providing signed informed consent and complying with protocol requirements, including reporting adverse events and attending follow-up visits.
Plans and Procedures
This is a phase IV, open-label clinical trial designed to investigate the immunogenicity of a licensed MF59 adjuvanted zoonotic influenza vaccine (H5N8) in adult participants. The trial compares immune responses between two groups: adults previously vaccinated in 2009 with a Matrix M adjuvanted virosomal influenza (H5N1) vaccine and H5-naïve adults who have not received prior H5N1 vaccination. The primary objective is to evaluate the humoral immune response to the Seqirus zoonotic influenza vaccine through measurement of haemagglutination inhibition (HI) and microneutralisation (MN) antibody titres against the vaccine virus strain (H5N8 clade 2.3.4.4b). The trial focuses on virus diseases and utilizes a suspension for injection in pre-filled syringe formulation containing influenza A/Astrakhan/3212/2020 (H5N8)-like strain (CBER-RG8A) (clade 2.3.4.4b) as the active substance, administered via intramuscular injection.
The trial is expected to commence recruitment in September 2025 and conclude in March 2031. Eligible participants must be between 35 and 70 years of age, overtly healthy or medically stable with chronic conditions that do not influence immune response, and have a body mass index between 18.0 and 35.0 kg/m². Female participants must be of non-childbearing potential or of childbearing potential with adequate contraception and a negative pregnancy test. Participants in the primed group must have received PanFluVac H5N1 Matrix M adjuvanted vaccine during a Phase I study in 2009. All participants must be capable of providing informed consent and complying with protocol requirements, including reporting adverse events and attending follow-up visits.
The trial involves administration of two doses of the zoonotic influenza vaccine, with a maximum daily dose of 7.50 µg and a maximum total dose of 15 µg over a treatment period of 5 days. The study schedule includes multiple visits for assessment of immunological parameters and safety monitoring. The baseline visit (Day 0) includes initial blood sampling for HI and MN antibody titre measurement and administration of the first vaccine dose. Follow-up visits occur at Day 7 and Day 28 after the first dose for blood sampling and immunological assessments. The second vaccine dose is administered at Day 28, followed by additional follow-up visits at Day 35 (7 days post-second dose) and Day 56 (28 days post-second dose) for further blood sampling and antibody titre evaluation. The end-of-study visit occurs at Day 56, marking the completion of participant involvement in the trial.
Primary endpoints include serum HI and MN antibody titres against the vaccine virus strain at baseline, 28 days after the first dose, and 28 days after the second dose. Secondary endpoints encompass HI antibody titres at Day 7 and Day 35, fold increases in antibody titres compared to baseline, and measures of serodetection, seroconversion, and seroprotection at multiple timepoints. The trial also evaluates immune responses against heterologous variant virus strains, including H5N1 clade 1 A/Vietnam/1194/2004 and H5N1 clade 2.2.1 A/turkey/Turkey/1/2005, through HI and MN antibody titre measurements. Safety assessments include monitoring and documentation of all serious adverse events (SAEs) from the day of vaccination through study completion, with particular attention to SAEs related to the study intervention.
Participant involvement spans approximately 56 days from the first vaccine administration to the final study visit. Conditions that may lead to early termination from the study include withdrawal of informed consent, development of medical conditions that preclude continued participation, occurrence of serious adverse events requiring discontinuation, pregnancy in female participants, significant protocol violations, or investigator decision based on safety concerns. The trial protocol requires participants to comply with all scheduled visits and procedures, report any adverse events promptly, and maintain adequate contraception where applicable throughout the study duration.
Treatment
The experimental treatment consists of **Zoonotic Influenza Vaccine Seqirus**, a **suspension for injection in pre-filled syringe** containing **zoonotic influenza vaccine (H5N8)** as **surface antigen, inactivated, adjuvanted**. The active substance is **influenza A/Astrakhan/3212/2020 (H5N8)-like strain (CBER-RG8A) (clade 2.3.4.4b)**. The vaccine is manufactured by Seqirus S.r.l. and holds the **marketing authorization number EU/1/23/1761/001**. The product is classified under **ATC code J07BB02** (influenza, purified antigen).
The vaccine is administered via **intramuscular injection**. The **maximum daily dose** is **7.50 micrograms**, with a **maximum total dose** of **15 micrograms** administered over the treatment period. The **maximum treatment period** is **5 months**. The vaccine contains **MF59 adjuvant** and is formulated as a structurally diverse substance vaccine. The pharmaceutical formulation is provided in a pre-filled syringe for single-use administration.
The study population includes two distinct groups: participants previously primed with the **PanFluVac Matrix M adjuvanted H5N1 influenza vaccine** in 2009, and **H5N1 vaccine-naive participants**. This design allows for comparison of immune responses between individuals with prior H5N1 vaccination exposure and those without such exposure. The previous vaccination with the Matrix M adjuvanted virosomal influenza (H5N1) vaccine serves as a relevant historical intervention for one cohort of study participants.
Efficacy
Efficacy will be assessed through evaluation of the humoral immune response to the zoonotic influenza vaccine. The primary endpoints include serum haemagglutination inhibition (HI) antibody titres against the vaccine virus strain (H5N8 clade 2.3.4.4b) measured at baseline (Day 0), 28 days after the first dose, and 28 days after the second dose (Day 56). Additionally, serum microneutralisation (MN) antibody titres against the vaccine virus strain (H5N8 clade 2.3.4.4b) will be measured at baseline (Day 0), 28 days after the first dose, and 28 days after the second dose (Day 56).
Secondary endpoints include serum HI antibody titres against the vaccine virus strain (H5N8 clade 2.3.4.4b) at 7 days after the first dose and 7 days after the second dose (Day 35). Fold increase in serum HI antibody titres against the virus strain will be evaluated at 7 days and 28 days after the first dose, and 7 days and 28 days after the second dose (Day 35, Day 56), compared to baseline (Day 0). Serodetection, seroconversion, and seroprotection based on serum HI antibody titres against the virus strain will be assessed at baseline (Day 0), 7 days and 28 days after the first dose, and 7 days and 28 days after the second dose (Day 35, Day 56). Serum MN antibody titres against the vaccine virus strain will be measured at 7 days after the first dose and 7 days after the second dose (Day 35).
Further secondary endpoints include serum HI antibody titres against heterologous variant virus strains, including H5N1 clade 1 A/Vietnam/1194/2004 and H5N1 clade 2.2.1 A/turkey/Turkey/1/2005, at baseline (Day 0), 7 days and 28 days after the first dose, and 7 days and 28 days after the second dose (Day 35, Day 56). Fold increase in serum HI antibody titres against these heterologous virus strains will be evaluated at 7 days and 28 days after the first dose, and 7 days and 28 days after the second dose (Day 56), compared to baseline (Day 0). Serodetection, seroconversion, and seroprotection based on serum HI antibody titres against heterologous virus strains will be assessed at baseline (Day 0), 7 days and 28 days after the first dose, and 7 days and 28 days after the second dose (Day 35, Day 56). Serum MN antibody titres against heterologous virus strains will be measured at baseline (Day 0), 7 days and 28 days after the first dose, and 7 days and 28 days after the second dose (Day 35, Day 56).
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 35 to 70 years of age inclusive, at the time of study intervention.
- Participants who are overtly healthy as determined by medical evaluation
- Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. report adverse events, return for follow-up visits).
- Participants who are medically stable in the opinion of the investigator at the time of the study intervention administration. Participants with chronic stable medical conditions with or without specific treatment, such as hypertension or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable and without potential influence on the immune response as to the opinion of the investigator.
- Body Mass Index within the range 18.0 to 35.0 kg/m 2 (inclusive)
- Female participants of non-childbearing potential may be enrolled in the study. Non- childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and post-menopause*. *A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.
- Female participants of childbearing potential may be enrolled in the study if the participant meets both of the following criteria: a. has practiced adequate contraception from 1 month prior to study intervention administration and agreed to continue adequate contraception until the end of the study. b. is not pregnant at the day of the study intervention administration, as per the medical anamnesis and urine pregnancy test.
- Capable of giving signed informed consent prior to performance of any study-specific procedure, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- For H5N1 primed participants, vaccination with PanFluVac H5N1 Matrix M adjuvanted vaccine in Phase I study in 2009.
Exclusion Criteria
- History of any reaction or hypersensitivity likely to be exacerbated by egg, chicken protein, ovalbumin, formaldehyde, hydrocortisone, kanamycin, neomycin sulphate, cetyltrimethylammonium bromide (CTAB), any component of the study intervention including a known history of severe allergic reaction (e.g., anaphylaxis).
- Any confirmed or suspected immunosuppressive condition, resulting from disease (e.g., current malignancy, human immunodeficiency virus) or immunosuppressive/cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), based on medical history and physical examination (no laboratory required).
- Recurrent history of uncontrolled neurological disorders or seizures. Participants with medically controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol.
- Serious or unstable chronic illness
- Any history of dementia or any medical condition that moderately or severely impairs cognition.
- Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study or impact the immune response such as autoimmune diseases.
- Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
- Any SAE attributed to a previous dose of an influenza vaccine.
- Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study.
- Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study intervention during the period beginning 30 days before the administration of the study intervention and ending at the completion of the study.
- Planned administration of a vaccine in the period starting 30 days before the study intervention administration and ending at day 56. If the study takes place in the autumn or winter seasonal influenza vaccine will be offered after day 56 samples.
- Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the completion of the study. a. Up to 3 months prior to the study intervention administration: i. For corticosteroids, this will mean prednisone equivalent ≥ 20 mg/day. Inhaled and topical steroids are allowed. ii. Administration of immunoglobulins and/or any blood products or plasma derivatives. b. Up to 6 months prior to the study intervention administration: long-acting immune-modifying drugs including among other immunotherapy (e.g., TNF- inhibitors), monoclonal antibodies and antitumoral medication.
- Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug/invasive medical device).
- Pregnant or lactating female participant.
- Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
- History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.
- Body Mass Index < 18.0 or > 35.0kg/m2
- Presence of a tattoo on the study intervention administration site that would prevent the assessment of the occurrence of local adverse events.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Norway | Not Recruiting | 01 Sept 2025 | 180 |
Sites & Investigators
Research 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 |
|---|---|---|---|---|---|---|
Zoonotic Influenza Vaccine Seqirus suspension for injection in pre-filled syringe Zoonotic influenza vaccine (H5N8)surface antigen, inactivated, adjuvanted | Test | SUSPENSION FOR INJECTION IN PRE-FILLED SYRINGE | INTRAMUSCULAR INJECTION | 07.50 | 5 | PRD10931113 |