Infections, Influenza, Human, Influenza in Birds, Orthomyxoviridae Infections, Respiratory Tract Diseases, Respiratory Tract Infections, RNA Virus Infections, Virus Diseases
Conditions
Keywords
Influenza, Pandemic, Vaccine, H5N1, H5N6, Flu, MF59, Avian
Brief summary
This is a Phase 2, randomized, multi-center study in approximately 300 adults who received 2 doses of aH5N1c or placebo in and completed the parent study V89\_18 in the \<65 years of age cohort. The study investigates whether two priming doses of MF59-adjuvanted H5N1 cell culture-derived vaccine (aH5N1c) followed by one or two booster vaccinations with a MF59-adjuvanted H5N6 cell culture derived vaccine (aH5N6c) 3 weeks apart elicit immune responses to the antigens used for priming (H5N1) and boosting (H5N6) after first and second heterologous booster vaccination. Eligible subjects, who received 2 doses of aH5N1c in the parent study V89\_18 are randomized in a 1:1 ratio to receive either two aH5N6c vaccinations, 3 weeks apart (group 1) or an aH5N6c vaccination on Day 1 and saline placebo on Day 22 (group 2). Eligible subjects, who received placebo in the parent study will receive two aH5N6c vaccinations, 3 weeks apart (group 3). After the second vaccine administration, subjects are monitored for approximately 6 months for safety and antibody persistence. The total study duration will be approximately 7 months per subject.
Interventions
BIOLOGICALaH5N6c on Day 1
MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 hemagglutinin (HA) (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume)
BIOLOGICALaH5N6c on Day 22
MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 HA (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume) given 3 weeks after the first aH5N6c vaccination
BIOLOGICALPlacebo on Day 22
Saline placebo (sterile, 0.5 mL) given 3 weeks after the aH5N6c vaccination
Sponsors
Seqirus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Eligible subjects, who received 2 doses of aH5N1c in the parent study V89\_18 are randomized in a 1:1 ratio to group 1 (two aH5N6c vaccinations, 3 weeks apart) or group 2 (aH5N6c vaccination and placebo, 3 weeks apart). Eligible subjects, who received placebo in the parent study are allocated to group 3 (two aH5N6c vaccinations, 3 weeks apart).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who received 2 doses of aH5N1c vaccine or placebo in and completed the parent study V89\_18 in the \<65 years of age cohort. * Individuals who can comply with study procedures including follow-up.
Exclusion criteria
* Females of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of contraceptive methods from at least 30 days prior to study entry and who do not plan to do so until at least 30 days after the last study vaccination. * Progressive, unstable or uncontrolled clinical conditions. * Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. * Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. * Abnormal function of the immune system. * History of any medical condition considered an adverse event of special interest (AESI). * Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent. * Subjects, who received an influenza H5 vaccine other than in the V89\_18 parent study or have a history of H5 influenza infection prior to enrollment. * Received an investigational or non-registered medicinal product within 30 days prior to informed consent. * Individuals who received any other vaccines \[except corona virus disease 2019 (COVID-19) vaccines\] within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any vaccine within 28 days from the study vaccination. * Receipt of any COVID-19 vaccine within 7 days prior to enrollment or plan to receive any COVID-19 vaccine within 7 days from study vaccination. * Acute (severe) febrile illness. * A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HI) Antibodies Against the H5N6 Strain | Day 1, Day 8, Day 22, Day 43 | GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the per-protocol set (PPS); definitions are provided in the Statistical Analysis Plan (SAP). The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| Geometric Mean Fold Increase (GMFI) of HI Antibodies Against the H5N6 Strain | Day 1, Day 8, Day 22, Day 43 | GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 compared to pre-vaccination (Day 1) Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain | Day 1, Day 8, Day 22, Day 43 | Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| Percentage of Subjects With Seroconversion Against the H5N6 Strain | Day 8, Day 22, Day 43 | Seroconversion 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer \<1:10 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMT of HI Antibodies Against the H5N1 Strain | Day 1, Day 8, Day 22, Day 43, Day 202 | GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| GMFI of HI Antibodies Against the H5N1 Strain | Day 1, Day 8, Day 22, Day 43, Day 202 | GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 compared to pre-vaccination (Day 1) Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| Percentage of Subjects With HI Titers ≥1:40 Against the H5N1 Strain | Day 1, Day 8, Day 22, Day 43, Day 202 | Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| Percentage of Subjects With Seroconversion Against the H5N1 Strain | Day 8, Day 22, Day 43, Day 202 | Seroconversion 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer \<1:10 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n\<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints. |
| GMT of HI Antibodies Against the H5N6 Strain | Day 202 | GMT 6 months post-vaccination 2 |
| GMFI of HI Antibodies Against the H5N6 Strain | Day 1, Day 202 | GMFI 6 months post-vaccination 2 compared to pre-vaccination (Day 1) |
| Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain | Day 202 | 6 months post-vaccination 2 |
| Percentage of Subjects With Seroconversion Against the H5N6 Strain | Day 202 | Seroconversion 6 months post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer \<1:10 |
| Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs) | Day 1 through Day 7 and Day 22 through Day 28 | For 7 days following each vaccination |
| Frequency and Severity of Unsolicited AEs | Day 1 through Day 43 | For 3 weeks following each vaccination |
| Frequency of Serious AEs (SAEs), AEs Leading to Withdrawal, AEs of Special Interest (AESI) and Medically Attended AEs (MAAEs) | Day 1 through Day 202 | From vaccination until study completion |
Countries
United States
Contacts
STUDY_CHAIRTherapeutic Area Head
Seqirus
Participant flow
Recruitment details
Subjects were enrolled between 18 July 2022 and 2 September 2022.
Pre-assignment details
All enrolled subjects have been assigned to one of the three treatment groups.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 10.67 |
| Age, Customized Age Group 18-49 years | 51 Participants |
| Age, Customized Age Group ≥50 years | 53 Participants |
| Body Mass Index | 28.95 kg/m2 STANDARD_DEVIATION 5.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Height | 168.00 cm STANDARD_DEVIATION 9.976 |
| Influenza Vaccination Within Past 2 Years No | 36 Participants |
| Influenza Vaccination Within Past 2 Years Yes | 54 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 74 Participants |
| Region of Enrollment United States | 101 participants |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 29 Participants |
| Weight | 82.97 kg STANDARD_DEVIATION 19.733 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 80 | 0 / 78 | 0 / 100 |
| other Total, other adverse events | 12 / 80 | 5 / 78 | 7 / 100 |
| serious Total, serious adverse events | 3 / 80 | 3 / 78 | 4 / 100 |
Outcome results
None listed