Influenza
Conditions
Keywords
Flu, Immunity, Virology, Investigational, Healthy Volunteer
Brief summary
Background: Influenza (flu) is a virus that infects people of all ages. Some people may have mild flu symptoms. Others may get very sick and even die from the flu. Flu vaccines help protect people against the flu, but if the flu strains in the vaccine are not a good match with the strains circulating in the community, the vaccine is not as effective. Researchers want to make flu vaccines that protect against changing flu strains. Objective: To test if a new flu vaccine is safe and if it creates an immune response. Eligibility: Healthy adults ages 18-55 who do not smoke and have not received a flu vaccine in the 8 weeks prior or a COVID-19 vaccine in the 4 weeks prior to enrollment. Design: Participants will be screened on a separate protocol. Participants will have 9 visits over 7 months. They will get a combination of study vaccine and/or placebo, both as a shot in the arm and as a spray into the nose, at 2 visits. For 7 days after getting the vaccines, they will take their temperature and complete online surveys at home to record any symptoms. At each visit, participants will have a physical exam and medical history. They will give blood and urine samples. They will have nasal testing. For this, a thin absorptive strip will be inserted into their nostril for 1 minute to collect mucus. At some visits, the inside of their nose will be wiped with a small brush to collect cells. For this, their nostril will be numbed to make it more comfortable. Some blood and nasal samples will be used for genetic testing. Participants who get flu-like symptoms during the study will be asked to collect nasal samples at home and send these samples back to NIH to test if they actually have the flu.
Detailed description
Study Description: This is a randomized, double-blinded, placebo-controlled, single-center, phase 1 clinical trial of beta-propiolactone (BPL)- inactivated quadruple influenza virus cocktail vaccine (BPL-1357) administered intramuscularly (IM) or intranasally (IN) in 2 doses 28 days apart. Participants will be randomized to one of three groups for treatment assignment. The primary hypothesis is that IN and IM BPL-1357 will be well tolerated. Objectives: Primary Objective: 1\. To assess the safety of BPL-1357 given IM or IN, compared to placebo. Secondary Objective: 1. To further assess the safety of BPL-1357 given IM or IN, compared to placebo. 2. To assess the immunogenicity of BPL-1357 given IM or IN, compared to placebo. Tertiary Objective: 1. To characterize the systemic and mucosal humoral immune responses induced by BPL-1357 given IM or IN, compared to placebo. 2. To further characterize the immune response induced by BPL-1357 given IM or IN through variable, diversity, and joining (VDJ) gene repertoire analysis, cytokine analysis, cytometry, transcriptomics, and assessment of T-cell responses. 3. To assess the rates of influenza disease among groups given IM or IN BPL-1357 compared to placebo. Endpoints: Primary Endpoints: 1. Type and severity (by grading) of adverse events (AEs) through vaccine 2 (V2) day 28 (D28) \[28 days after vaccine dose 2\]. 2. Type of serious adverse events (SAEs) through V2D28 \[28 days after vaccine dose 2\]. Secondary Endpoints: 1. Safety 1. Type and severity (by grading) of AEs through V2D182 \[182 days after vaccine dose 2\]. 2. Type of SAEs through V2D182 \[182 days after vaccine dose 2\]. 2. Immunogenicity 1. Antibodies against H1, H3, H5, and H7 head and stalk as measured by hemagglutination inhibition (HAI) or enzyme-linked immunosorbent assay (ELISA) from blood and mucosal samples at V2D28. 2. Antibodies against N1, N3, N8, and N9 as measured by neuraminidase inhibition (NAI) or ELISA from blood and mucosal samples at V2D28. Tertiary Endpoints: 1. Additional antibody titer characterization via: 1. Antibodies against H1, H3, H5, and H7 head and stalk as measured by HAI or ELISA from blood and mucosal samples at V1D7, V1D14, V1D28, V2D7, V2D14, V2D56, and V2D182. 2. Antibodies against N1, N3, N8, and N9 as measured by NAI or ELISA from blood and mucosal samples at V1D7, V1D14, V1D28, V2D7, V2D14, V2D56, and V2D182. 2. Additional immune response characterization via: 1. VDJ gene repertoire analysis. 2. Cytokine analysis. 3. Flow cytometric phenotyping of lymphocytes. 4. Transcriptomic gene expression. 5. T-cell responses. 3. Influenza disease
Interventions
OTHERIN Placebo
The placebo is normal saline in two syringes administered IN.
OTHERIM Placebo
The placebo is normal saline in a syringe administered IM.
DRUGBPL-1357
BPL-1357 contains 4 whole inactivated avian influenza viruses: A /Environment /Maryland/261/2006 H7N3, A/Mallard /Maryland/802/2007 H5N1, A/Pintail/Ohio /339/1987 H3N8, and A/Mallard/Ohio /265/1987 H1N9. It is administered either IM or IN depending on the assigned treatment group.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: Individuals must meet all of the following criteria to be eligible for study participation: * 18 and \<= 55 years of age. * Non-smoker (tobacco and cannabis) and does not use vape or e-cigarette products. * Has not received influenza vaccination of any type in the 8 weeks prior to enrollment and willing to not receive influenza vaccination of any type until after the V2D56 visit. Participants who enroll in our study will be informed of the Centers for Disease Control and Prevention (CDC) recommendation to receive seasonal influenza vaccination annually. * Has not received Coronavirus Disease 19 (COVID-19) vaccination of any type in the 4 weeks prior to enrollment and willing to not receive COVID-19 vaccination of any type until after the V2D28 visit. Participants who enroll in our study who are interested in getting a COVID-19 vaccination will be counselled to receive it prior to enrolling into our study. * A female participant is eligible for this study if she is not pregnant or breastfeeding and meets one of the following criteria, beginning at least 4 weeks prior to enrollment through the end of the study period (V2D182): * Is infertile, including postmenopausal status (as defined by no menses for \>= 1 year) or history of hysterectomy or bilateral oophorectomy. * Agrees to practice abstinence. * Agrees that, with heterosexual intercourse with a fertile male partner, she will use an acceptable form of contraception and her male partner will use a condom with spermicide. Acceptable effective methods of female contraception include the following: bilateral tubal ligation, implant of levonorgestrel, injectable progestogen, intrauterine device, oral contraceptive pills, and diaphragm with spermicide. * Able to provide informed consent. * Able to speak English. * Human immunodeficiency virus (HIV) uninfected with a negative test within 60 days of enrollment. * Does not use IN medications (including but not limited to nasal sprays, sinus rinses), over-the-counter medications (including but not limited to aspirin, decongestants, antihistamines, and other nonsteroidal anti-inflammatory drugs), and herbal medications (including but not limited to herbal tea or St. John s Wort) within 14 days prior to study enrollment, and agrees not to use these mediations through the final study visit, unless approved by the investigator. * Agrees not to donate blood or blood products from 3 months prior to enrollment through the final study visit.
Exclusion criteria
Individuals meeting any of the following criteria will be excluded from study participation: * Presence of self-reported or medically documented significant medical condition including but not limited to: * Chronic pulmonary disease (e.g., asthma, emphysema). * Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects). * Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies). * Immunosuppression, immune deficiency, or ongoing malignancy. * Neurological and neurodevelopmental conditions (e.g., Bell s palsy, cerebral palsy, epilepsy, stroke, seizures). * Postinfectious or postvaccine neurological sequelae including GBS. * Body mass index (BMI) \<= 18 and \>= 35. * Acute illness within 7 days prior to enrollment. * Individuals who have grade 2 or above clinically significant laboratory values outside the limits thus specified by normal laboratory parameters. * Known allergy to influenza vaccination or excipients contained in the influenza vaccine used. * Known allergy to lidocaine or phenylephrine. * Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment. * Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment. * Receipt of any unlicensed vaccine within 6 months prior to enrollment, not including COVID-19 vaccines under Emergency Use Authorization. * Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment, or positive urine test for drugs of abuse (i.e., amphetamines, cocaine metabolites, benzodiazepines, opiates, or tetrahydrocannabinol) prior to vaccination on V1D0. * Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the principal investigator (PI) to be a contraindication to protocol participation. * History of angioedema or anaphylaxis. * History of SARS-COV-2 infection with residual or ongoing symptoms. * Any condition or event that, in the judgment of the PI, is a contraindication to protocol participation or impairs the participant s ability to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Serious Adverse Event | V2D28 (Day 56) | Type of SAEs through day V2D28. |
| Safety - Adverse Events | V2D28 (Day 56) | Type and severity (by grading) of intervention-related AEs through day V2D28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Serious Adverse Event | V2D182 (Day 210) | Type of SAEs through day V2D182 |
| Safety - Adverse Events | V2D182 (Day 210) | Type and severity (by grading) of AEs through day V2D182 |
| Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | V2D28 (Day 56) | Antibodies against H1, H3, H5, and H7 head and stalk as measured by HAI or ELISA from blood and mucosal samples at V2D28 |
| Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | V2D28 (Day 56) | Antibodies against N1, N3, N8, and N9 as measured by NAI or ELISA from blood and mucosal samples at V2D28 |
Countries
United States
Participant flow
Recruitment details
Participants were identified and recruited from the community through multiple methodologies including local advertisement, direct contact of prior study participants, and word of mouth advertisement. Seventy-eight participants were screened between May 2022 and October 2022 on a separate screening protocol (11-I-0183).
Pre-assignment details
Forty-five participants were enrolled and randomized to the three study arms.
Participants by arm
| Arm | Count |
|---|---|
| Group A 15 participants receiving IM BPL1357 and IN Placebo. | 15 |
| Group B 15 participants receiving IN BPL1357 and IM Placebo. | 15 |
| Group C 15 participants receiving IM and IN placebo. | 15 |
| Total | 45 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Total |
|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 8.4 | 30.3 years STANDARD_DEVIATION 10.2 | 27.5 years STANDARD_DEVIATION 6 | 30.6 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 14 Participants | 15 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 2 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 7 Participants | 9 Participants | 26 Participants |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 8 Participants | 27 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 7 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 15 / 15 | 15 / 15 | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Safety - Adverse Events
Type and severity (by grading) of intervention-related AEs through day V2D28.
Time frame: V2D28 (Day 56)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A | Safety - Adverse Events | Arthralgia | 1 Participants |
| Group A | Safety - Adverse Events | Hyperglycemia | 1 Participants |
| Group A | Safety - Adverse Events | Hypokalemia | 0 Participants |
| Group A | Safety - Adverse Events | Pruritus | 0 Participants |
| Group A | Safety - Adverse Events | Fever | 0 Participants |
| Group A | Safety - Adverse Events | Nausea | 1 Participants |
| Group A | Safety - Adverse Events | Myalgia | 4 Participants |
| Group A | Safety - Adverse Events | Eye discomfort | 0 Participants |
| Group A | Safety - Adverse Events | Decreased appetite | 0 Participants |
| Group A | Safety - Adverse Events | Fatigue | 10 Participants |
| Group A | Safety - Adverse Events | Erythema | 0 Participants |
| Group A | Safety - Adverse Events | Hemoglobin decreased | 0 Participants |
| Group A | Safety - Adverse Events | Paresthesia | 1 Participants |
| Group A | Safety - Adverse Events | Dizziness | 0 Participants |
| Group A | Safety - Adverse Events | Alanine aminotransferase increased | 0 Participants |
| Group A | Safety - Adverse Events | Sore Throat | 3 Participants |
| Group A | Safety - Adverse Events | Diarrhea | 0 Participants |
| Group A | Safety - Adverse Events | Aspartate aminotransferase increased | 0 Participants |
| Group A | Safety - Adverse Events | WBC increased | 0 Participants |
| Group A | Safety - Adverse Events | Blood bilirubin increased | 0 Participants |
| Group A | Safety - Adverse Events | Pain | 0 Participants |
| Group A | Safety - Adverse Events | Hoarseness | 1 Participants |
| Group A | Safety - Adverse Events | WBC decreased | 1 Participants |
| Group A | Safety - Adverse Events | Numbness | 1 Participants |
| Group A | Safety - Adverse Events | Rhinorrhea | 1 Participants |
| Group A | Safety - Adverse Events | Injection Site Pain | 14 Participants |
| Group A | Safety - Adverse Events | Muscle weakness lower limb | 0 Participants |
| Group A | Safety - Adverse Events | Nasal congestion | 0 Participants |
| Group A | Safety - Adverse Events | Sneezing | 1 Participants |
| Group A | Safety - Adverse Events | Migraine | 1 Participants |
| Group A | Safety - Adverse Events | Neutrophil count decreased | 2 Participants |
| Group A | Safety - Adverse Events | Vertigo | 0 Participants |
| Group A | Safety - Adverse Events | Injection site ecchymosis | 1 Participants |
| Group A | Safety - Adverse Events | Chills | 0 Participants |
| Group A | Safety - Adverse Events | Headache | 8 Participants |
| Group A | Safety - Adverse Events | Hypophosphatemia | 1 Participants |
| Group A | Safety - Adverse Events | Cough | 0 Participants |
| Group B | Safety - Adverse Events | Paresthesia | 0 Participants |
| Group B | Safety - Adverse Events | Arthralgia | 3 Participants |
| Group B | Safety - Adverse Events | Sneezing | 1 Participants |
| Group B | Safety - Adverse Events | Fatigue | 8 Participants |
| Group B | Safety - Adverse Events | Injection Site Pain | 6 Participants |
| Group B | Safety - Adverse Events | Headache | 3 Participants |
| Group B | Safety - Adverse Events | Myalgia | 3 Participants |
| Group B | Safety - Adverse Events | Sore Throat | 2 Participants |
| Group B | Safety - Adverse Events | Hoarseness | 3 Participants |
| Group B | Safety - Adverse Events | Rhinorrhea | 2 Participants |
| Group B | Safety - Adverse Events | Nasal congestion | 1 Participants |
| Group B | Safety - Adverse Events | Neutrophil count decreased | 0 Participants |
| Group B | Safety - Adverse Events | Chills | 0 Participants |
| Group B | Safety - Adverse Events | Cough | 1 Participants |
| Group B | Safety - Adverse Events | Hypokalemia | 2 Participants |
| Group B | Safety - Adverse Events | Nausea | 1 Participants |
| Group B | Safety - Adverse Events | Decreased appetite | 0 Participants |
| Group B | Safety - Adverse Events | Hemoglobin decreased | 1 Participants |
| Group B | Safety - Adverse Events | Alanine aminotransferase increased | 0 Participants |
| Group B | Safety - Adverse Events | Aspartate aminotransferase increased | 0 Participants |
| Group B | Safety - Adverse Events | Blood bilirubin increased | 0 Participants |
| Group B | Safety - Adverse Events | Diarrhea | 1 Participants |
| Group B | Safety - Adverse Events | Dizziness | 1 Participants |
| Group B | Safety - Adverse Events | Erythema | 1 Participants |
| Group B | Safety - Adverse Events | Eye discomfort | 1 Participants |
| Group B | Safety - Adverse Events | Fever | 1 Participants |
| Group B | Safety - Adverse Events | Hyperglycemia | 0 Participants |
| Group B | Safety - Adverse Events | Hypophosphatemia | 0 Participants |
| Group B | Safety - Adverse Events | Injection site ecchymosis | 0 Participants |
| Group B | Safety - Adverse Events | Migraine | 0 Participants |
| Group B | Safety - Adverse Events | Muscle weakness lower limb | 1 Participants |
| Group B | Safety - Adverse Events | Numbness | 0 Participants |
| Group B | Safety - Adverse Events | Pain | 1 Participants |
| Group B | Safety - Adverse Events | Pruritus | 1 Participants |
| Group B | Safety - Adverse Events | Vertigo | 1 Participants |
| Group B | Safety - Adverse Events | WBC decreased | 0 Participants |
| Group B | Safety - Adverse Events | WBC increased | 0 Participants |
| Group C | Safety - Adverse Events | Fever | 0 Participants |
| Group C | Safety - Adverse Events | Cough | 2 Participants |
| Group C | Safety - Adverse Events | WBC decreased | 0 Participants |
| Group C | Safety - Adverse Events | Hyperglycemia | 0 Participants |
| Group C | Safety - Adverse Events | Chills | 3 Participants |
| Group C | Safety - Adverse Events | Pruritus | 0 Participants |
| Group C | Safety - Adverse Events | Hypophosphatemia | 0 Participants |
| Group C | Safety - Adverse Events | Neutrophil count decreased | 2 Participants |
| Group C | Safety - Adverse Events | Injection Site Pain | 0 Participants |
| Group C | Safety - Adverse Events | Injection site ecchymosis | 0 Participants |
| Group C | Safety - Adverse Events | Nasal congestion | 3 Participants |
| Group C | Safety - Adverse Events | Arthralgia | 1 Participants |
| Group C | Safety - Adverse Events | Migraine | 0 Participants |
| Group C | Safety - Adverse Events | Rhinorrhea | 2 Participants |
| Group C | Safety - Adverse Events | Vertigo | 0 Participants |
| Group C | Safety - Adverse Events | Muscle weakness lower limb | 0 Participants |
| Group C | Safety - Adverse Events | Hoarseness | 1 Participants |
| Group C | Safety - Adverse Events | Fatigue | 9 Participants |
| Group C | Safety - Adverse Events | Numbness | 0 Participants |
| Group C | Safety - Adverse Events | Sore Throat | 4 Participants |
| Group C | Safety - Adverse Events | Aspartate aminotransferase increased | 1 Participants |
| Group C | Safety - Adverse Events | WBC increased | 1 Participants |
| Group C | Safety - Adverse Events | Blood bilirubin increased | 1 Participants |
| Group C | Safety - Adverse Events | Alanine aminotransferase increased | 1 Participants |
| Group C | Safety - Adverse Events | Pain | 0 Participants |
| Group C | Safety - Adverse Events | Diarrhea | 0 Participants |
| Group C | Safety - Adverse Events | Hemoglobin decreased | 1 Participants |
| Group C | Safety - Adverse Events | Myalgia | 2 Participants |
| Group C | Safety - Adverse Events | Dizziness | 0 Participants |
| Group C | Safety - Adverse Events | Decreased appetite | 2 Participants |
| Group C | Safety - Adverse Events | Sneezing | 4 Participants |
| Group C | Safety - Adverse Events | Erythema | 0 Participants |
| Group C | Safety - Adverse Events | Nausea | 1 Participants |
| Group C | Safety - Adverse Events | Paresthesia | 0 Participants |
| Group C | Safety - Adverse Events | Eye discomfort | 0 Participants |
| Group C | Safety - Adverse Events | Hypokalemia | 1 Participants |
| Group C | Safety - Adverse Events | Headache | 6 Participants |
Primary
Safety - Serious Adverse Event
Type of SAEs through day V2D28.
Time frame: V2D28 (Day 56)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Safety - Serious Adverse Event | 0 SAEs |
| Group B | Safety - Serious Adverse Event | 0 SAEs |
| Group C | Safety - Serious Adverse Event | 0 SAEs |
Secondary
Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin
Antibodies against H1, H3, H5, and H7 head and stalk as measured by HAI or ELISA from blood and mucosal samples at V2D28
Time frame: V2D28 (Day 56)
Population: One participant in Group A missed their V2D28 visit and did not provide samples for analysis at this timepoints. One participant in group B withdrew consent to use samples after study completion.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H1 IgG | 2765 ELISA Titers | 95% Confidence Interval 4339 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H3 IgG | 1104 ELISA Titers | 95% Confidence Interval 973 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H5 IgG | 1010 ELISA Titers | 95% Confidence Interval 1425 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H7 IgG | 638 ELISA Titers | 95% Confidence Interval 524 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H1 IgA | 0.446 ELISA Titers | 95% Confidence Interval 0.52 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H3 IgA | 0.525 ELISA Titers | 95% Confidence Interval 0.218 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H5 IgA | 0.213 ELISA Titers | 95% Confidence Interval 0.332 |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H7 IgA | 0.279 ELISA Titers | 95% Confidence Interval 0.316 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H5 IgG | 365 ELISA Titers | 95% Confidence Interval 310 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H5 IgA | 0.377 ELISA Titers | 95% Confidence Interval 0.345 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H7 IgG | 169 ELISA Titers | 95% Confidence Interval 421 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H1 IgA | 0.556 ELISA Titers | 95% Confidence Interval 0.325 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H3 IgA | 0.564 ELISA Titers | 95% Confidence Interval 0.279 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H1 IgG | 2093 ELISA Titers | 95% Confidence Interval 2519 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H3 IgG | 379 ELISA Titers | 95% Confidence Interval 686 |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H7 IgA | 0.357 ELISA Titers | 95% Confidence Interval 0.131 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H5 IgG | 284 ELISA Titers | 95% Confidence Interval 145 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H3 IgG | 333 ELISA Titers | 95% Confidence Interval 242 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H1 IgG | 1776 ELISA Titers | 95% Confidence Interval 1514 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Serum Anti-H7 IgG | 141 ELISA Titers | 95% Confidence Interval 123 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H5 IgA | 0.264 ELISA Titers | 95% Confidence Interval 0.291 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H3 IgA | 0.543 ELISA Titers | 95% Confidence Interval 0.267 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H1 IgA | 0.504 ELISA Titers | 95% Confidence Interval 0.223 |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Hemagglutinin | Nasal Anti-H7 IgA | 0.329 ELISA Titers | 95% Confidence Interval 0.21 |
Secondary
Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase
Antibodies against N1, N3, N8, and N9 as measured by NAI or ELISA from blood and mucosal samples at V2D28
Time frame: V2D28 (Day 56)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N1 IgG | 222 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N3 IgG | 43 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N8 IgG | 25 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N9 IgG | 25 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N1 IgA | 0.171 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N3 IgA | 0.091 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N8 IgA | 0.139 ELISA Titers |
| Group A | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N9 IgA | 0.124 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N8 IgG | 15 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N8 IgA | 0.238 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N9 IgG | 12 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N1 IgA | 0.405 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N9 IgA | 0.164 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N3 IgA | 0.132 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N1 IgG | 266 ELISA Titers |
| Group B | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N3 IgG | 30 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N3 IgG | 20 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N9 IgA | 0.240 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N1 IgG | 282 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N9 IgG | 13 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N8 IgA | 0.288 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N3 IgA | 0.142 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Nasal Anti-N1 IgA | 0.308 ELISA Titers |
| Group C | Immunogenicity - Systemic and Mucosal Immune Responses Against Neuraminidase | Serum Anti-N8 IgG | 23 ELISA Titers |
Secondary
Safety - Adverse Events
Type and severity (by grading) of AEs through day V2D182
Time frame: V2D182 (Day 210)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A | Safety - Adverse Events | WBC decreased | 1 Participants |
| Group A | Safety - Adverse Events | Hyperglycemia | 1 Participants |
| Group A | Safety - Adverse Events | Hypokalemia | 0 Participants |
| Group A | Safety - Adverse Events | Fatigue | 10 Participants |
| Group A | Safety - Adverse Events | Fever | 0 Participants |
| Group A | Safety - Adverse Events | Nausea | 1 Participants |
| Group A | Safety - Adverse Events | Sneezing | 1 Participants |
| Group A | Safety - Adverse Events | Eye discomfort | 0 Participants |
| Group A | Safety - Adverse Events | Decreased appetite | 0 Participants |
| Group A | Safety - Adverse Events | Headache | 8 Participants |
| Group A | Safety - Adverse Events | Erythema | 0 Participants |
| Group A | Safety - Adverse Events | Hemoglobin decreased | 0 Participants |
| Group A | Safety - Adverse Events | Paresthesia | 1 Participants |
| Group A | Safety - Adverse Events | Dizziness | 0 Participants |
| Group A | Safety - Adverse Events | Alanine aminotransferase increased | 0 Participants |
| Group A | Safety - Adverse Events | Arthralgia | 1 Participants |
| Group A | Safety - Adverse Events | Diarrhea | 0 Participants |
| Group A | Safety - Adverse Events | Aspartate aminotransferase increased | 0 Participants |
| Group A | Safety - Adverse Events | Injection site pain | 14 Participants |
| Group A | Safety - Adverse Events | Blood bilirubin increased | 0 Participants |
| Group A | Safety - Adverse Events | Pain | 0 Participants |
| Group A | Safety - Adverse Events | Hoarseness | 1 Participants |
| Group A | Safety - Adverse Events | Vertigo | 0 Participants |
| Group A | Safety - Adverse Events | Numbness | 1 Participants |
| Group A | Safety - Adverse Events | Rhinorrhea | 1 Participants |
| Group A | Safety - Adverse Events | Myalgia | 4 Participants |
| Group A | Safety - Adverse Events | Muscle weakness lower limb | 0 Participants |
| Group A | Safety - Adverse Events | Nasal congestion | 0 Participants |
| Group A | Safety - Adverse Events | WBC increased | 0 Participants |
| Group A | Safety - Adverse Events | Migraine | 1 Participants |
| Group A | Safety - Adverse Events | Neutrophil count decreased | 2 Participants |
| Group A | Safety - Adverse Events | Pruritus | 0 Participants |
| Group A | Safety - Adverse Events | Injection site ecchymosis | 1 Participants |
| Group A | Safety - Adverse Events | Chills | 0 Participants |
| Group A | Safety - Adverse Events | Sore throat | 3 Participants |
| Group A | Safety - Adverse Events | Hypophosphatemia | 1 Participants |
| Group A | Safety - Adverse Events | Cough | 0 Participants |
| Group B | Safety - Adverse Events | Paresthesia | 0 Participants |
| Group B | Safety - Adverse Events | Fatigue | 8 Participants |
| Group B | Safety - Adverse Events | Injection site pain | 6 Participants |
| Group B | Safety - Adverse Events | Headache | 3 Participants |
| Group B | Safety - Adverse Events | Myalgia | 3 Participants |
| Group B | Safety - Adverse Events | Sore throat | 2 Participants |
| Group B | Safety - Adverse Events | Sneezing | 1 Participants |
| Group B | Safety - Adverse Events | Arthralgia | 3 Participants |
| Group B | Safety - Adverse Events | Hoarseness | 3 Participants |
| Group B | Safety - Adverse Events | Rhinorrhea | 2 Participants |
| Group B | Safety - Adverse Events | Nasal congestion | 1 Participants |
| Group B | Safety - Adverse Events | Neutrophil count decreased | 0 Participants |
| Group B | Safety - Adverse Events | Chills | 0 Participants |
| Group B | Safety - Adverse Events | Cough | 1 Participants |
| Group B | Safety - Adverse Events | Hypokalemia | 2 Participants |
| Group B | Safety - Adverse Events | Nausea | 1 Participants |
| Group B | Safety - Adverse Events | Decreased appetite | 0 Participants |
| Group B | Safety - Adverse Events | Hemoglobin decreased | 1 Participants |
| Group B | Safety - Adverse Events | Alanine aminotransferase increased | 0 Participants |
| Group B | Safety - Adverse Events | Aspartate aminotransferase increased | 0 Participants |
| Group B | Safety - Adverse Events | Blood bilirubin increased | 0 Participants |
| Group B | Safety - Adverse Events | Diarrhea | 1 Participants |
| Group B | Safety - Adverse Events | Dizziness | 1 Participants |
| Group B | Safety - Adverse Events | Erythema | 1 Participants |
| Group B | Safety - Adverse Events | Eye discomfort | 1 Participants |
| Group B | Safety - Adverse Events | Fever | 1 Participants |
| Group B | Safety - Adverse Events | Hyperglycemia | 0 Participants |
| Group B | Safety - Adverse Events | Hypophosphatemia | 0 Participants |
| Group B | Safety - Adverse Events | Injection site ecchymosis | 0 Participants |
| Group B | Safety - Adverse Events | Migraine | 0 Participants |
| Group B | Safety - Adverse Events | Muscle weakness lower limb | 1 Participants |
| Group B | Safety - Adverse Events | Numbness | 0 Participants |
| Group B | Safety - Adverse Events | Pain | 1 Participants |
| Group B | Safety - Adverse Events | Pruritus | 1 Participants |
| Group B | Safety - Adverse Events | Vertigo | 1 Participants |
| Group B | Safety - Adverse Events | WBC decreased | 0 Participants |
| Group B | Safety - Adverse Events | WBC increased | 0 Participants |
| Group C | Safety - Adverse Events | Fever | 0 Participants |
| Group C | Safety - Adverse Events | Cough | 2 Participants |
| Group C | Safety - Adverse Events | WBC decreased | 0 Participants |
| Group C | Safety - Adverse Events | Hyperglycemia | 0 Participants |
| Group C | Safety - Adverse Events | Chills | 3 Participants |
| Group C | Safety - Adverse Events | Pruritus | 0 Participants |
| Group C | Safety - Adverse Events | Hypophosphatemia | 0 Participants |
| Group C | Safety - Adverse Events | Neutrophil count decreased | 2 Participants |
| Group C | Safety - Adverse Events | Headache | 6 Participants |
| Group C | Safety - Adverse Events | Injection site ecchymosis | 0 Participants |
| Group C | Safety - Adverse Events | Nasal congestion | 3 Participants |
| Group C | Safety - Adverse Events | Fatigue | 9 Participants |
| Group C | Safety - Adverse Events | Migraine | 0 Participants |
| Group C | Safety - Adverse Events | Rhinorrhea | 2 Participants |
| Group C | Safety - Adverse Events | Vertigo | 0 Participants |
| Group C | Safety - Adverse Events | Muscle weakness lower limb | 0 Participants |
| Group C | Safety - Adverse Events | Hoarseness | 1 Participants |
| Group C | Safety - Adverse Events | Injection site pain | 0 Participants |
| Group C | Safety - Adverse Events | Numbness | 0 Participants |
| Group C | Safety - Adverse Events | Arthralgia | 1 Participants |
| Group C | Safety - Adverse Events | Aspartate aminotransferase increased | 1 Participants |
| Group C | Safety - Adverse Events | WBC increased | 1 Participants |
| Group C | Safety - Adverse Events | Blood bilirubin increased | 1 Participants |
| Group C | Safety - Adverse Events | Alanine aminotransferase increased | 1 Participants |
| Group C | Safety - Adverse Events | Pain | 0 Participants |
| Group C | Safety - Adverse Events | Diarrhea | 0 Participants |
| Group C | Safety - Adverse Events | Hemoglobin decreased | 1 Participants |
| Group C | Safety - Adverse Events | Sneezing | 4 Participants |
| Group C | Safety - Adverse Events | Dizziness | 0 Participants |
| Group C | Safety - Adverse Events | Decreased appetite | 2 Participants |
| Group C | Safety - Adverse Events | Sore throat | 4 Participants |
| Group C | Safety - Adverse Events | Erythema | 0 Participants |
| Group C | Safety - Adverse Events | Nausea | 1 Participants |
| Group C | Safety - Adverse Events | Paresthesia | 0 Participants |
| Group C | Safety - Adverse Events | Eye discomfort | 0 Participants |
| Group C | Safety - Adverse Events | Hypokalemia | 1 Participants |
| Group C | Safety - Adverse Events | Myalgia | 2 Participants |
Secondary
Safety - Serious Adverse Event
Type of SAEs through day V2D182
Time frame: V2D182 (Day 210)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Safety - Serious Adverse Event | 0 SAEs |
| Group B | Safety - Serious Adverse Event | 0 SAEs |
| Group C | Safety - Serious Adverse Event | 0 SAEs |