Healthy Volunteers, Influenza
Conditions
Brief summary
The study aims to evaluate an egg-based H5N8 influenza vaccine up to 3 dose levels (low, medium, and high dose) given with or without adjuvant to see if the adjuvant improves vaccine effectiveness. The study will enroll healthy adults aged 18 years and over. Participants will receive 2 injections in their arm of either one of the 3 dose levels of the study vaccine (low, medium, or high dose) with the adjuvant or the unadjuvanted vaccine (high dose). Study duration per participant: approximately 14 months (including screening visit).
Interventions
BIOLOGICALFlu H5 egg pandemic low dose vaccine, with adjuvant
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
BIOLOGICALFlu H5 Egg Pandemic medium dose vaccine, with adjuvant
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
BIOLOGICALFlu H5 Egg Pandemic high dose vaccine, with adjuvant
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
BIOLOGICALFlu H5 Egg Pandemic high dose vaccine, without adjuvant
Pharmaceutical form: Suspension for injection Route of administration: Intramuscular (IM)
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Observer-blind study. Participants, Sponsor study staff, investigators and study staff, will remain blinded during the study conduct, except dedicated study staff preparing/administering the study interventions and who are not involved in the safety evaluation; dedicated Sponsor staff involved in Safety Governance for the early safety data review (ESDRs) and, if necessary, in case of a safety signal; dedicated Sponsor staff who will be unblinded for ESDRs and interim analyses; dedicated monitoring staff performing unblinded IMP monitoring tasks.
Intervention model description
Parallel, multi-center, controlled study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 years or above on the day of inclusion * Participants who are healthy as determined by medical evaluation including medical history * Not pregnant/breastfeeding; non-childbearing potential or uses effective contraception/abstinence from ≥4 weeks before the first study intervention dose to ≥8 weeks after the last dose * Informed consent form has been signed and dated * Able to attend all scheduled visits and to comply with all study procedures * Covered by health insurance, if required by local regulations
Exclusion criteria
* Known or suspected immunodeficiency; immunosuppressive therapy in past 6 months; or long-term systemic corticosteroid (eg, prednisone for more than 2 weeks in the past 3 months) * Known hepatitis B or hepatitis C infection (based on medical history) * Known personal or family history of previous episodes of Guillan-Barré syndrome (GBS), neuritis (including Bell's palsy), convulsions, encephalitis, transverse myelitis, and vasculitis * Known systemic hypersensitivity to any of the study intervention components or history of life-threatening reaction to the study interventions or products with same substances * Self-reported thrombocytopenia contraindicating intramuscular (IM) injection based on investigator's judgment * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM injection based on investigator's judgment * Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion * History of A/H5 infection prior to the study participation * Moderate or severe acute illness/infection (per investigator judgment)/fever (≥ 38.0°C \[≥ 100.4°F\]) on study intervention day. Include participant only after the condition or fever has resolved * Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion * Any vaccine given 4 weeks before first study intervention or any planned vaccination to be given prior to Day 43 (ie, approximately 21 days after the second study intervention) * Previous vaccination against A(H5) with an investigational or marketed vaccine. This includes, but is not limited to, influenza subtypes A(H5N1), A(H5N8), and A(H5N6) * Has received a blood transfusion or blood-derived products, including immunoglobulins in the past 3 months * Participation in another clinical study for a vaccine, drug, medical device, or medical procedure within 4 weeks before enrollment or planned participation during the present study period * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily * Is an investigator, investigator/study center employee, or immediate family member (parent, spouse, natural/adopted child) of the investigator/employee with direct involvement in the study * Any screening safety laboratory parameters out of normal ranges and assessed as \> Grade 2 The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with immediate Adverse Events (AEs) | Within 30 minutes after each vaccination | Immediate adverse events are medically relevant unsolicited systemic adverse events reported in the 30 minutes after vaccination |
| Number of participants experiencing solicited administration site reactions (pre-listed in the participant diary and case report form [CRF]) | Within 8 days of each vaccination, including the day of vaccination | A solicited reaction is an adverse reaction (sign or symptom) observed and reported under the conditions pre-listed (for example: injection site pain or headache). Solicited administration site reactions are reactions at and around the injection/administration site |
| Number of participants experiencing solicited systemic reactions (pre-listed in the participant diary and CRF) | Within 8 days of each vaccination, including the day of vaccination | All solicited reactions that are not solicited injection or administration site reactions |
| Number of participants experiencing unsolicited AEs | Within 21 days after the first vaccination, including the day of the first vaccination, and within 28 days after the second vaccination, including the day of the second vaccination | Unsolicited AE: an observed AE that does not fulfill the conditions of solicited reactions |
| Number of participants experiencing Medically Attended Adverse Events (MAAEs) | From Day 01 until the end of the study, approximately 14 months | MAAEs are collected throughout the study |
| Number of participants experiencing Adverse Events of Special Interest (AESIs) | From Day 01 until the end of the study, approximately 14 months | AESIs are collected throughout the study |
| Number of participants experiencing Serious Adverse Events (SAEs) | From Day 01 until the end of the study, approximately 14 months | SAEs are collected throughout the study |
| Number of participants experiencing out-of-range biological test results (including shift from baseline values) | Up to 8 days after each vaccination | Safety laboratory assessments will include clinical chemistry and hematology |
| Number of participants experiencing AEs leading to discontinuation | From Day 01 until the end of the study, approximately 14 months | AEs leading to discontinuation are collected throughout the study |
| Geometric mean titer of hemagglutination inhibition (HAI) assay antibody (Ab) titer | Day 01 and Day 43 | Influenza vaccine antibody titers are measured by HAI assay |
| Number of participants with HAI Ab titer ≥ 40 (1 dilution [dil]; ie, seroprotection) | Day 43 | Influenza vaccine antibody titers are measured by HAI assay |
| Number of participants with seroconversion | Day 01 and Day 43 | Seroconversion is defined as HAI Ab titer \< 10 (1/dil) on Day 01 and post-injection titer ≥ 40 (1/dil) on Day 43; or defined as HAI Ab titer ≥ 10 (1/dil) on Day 01 and a ≥ 4-fold increase in titer (1/dil) on Day 43 |
| Geometric mean titer ratio of individual HAI Ab titer ratio Day 43/Day 01 | Day 01 and Day 43 | Influenza vaccine antibody titers are measured by HAI assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric mean titer of hemagglutination inhibition (HAI) assay antibody (Ab) titer obtained on Day 01, Day 22, Day 43, Day 202 | Day 01, Day 22, Day 43, Day 202 | Influenza vaccine antibody titers are measured by HAI assay |
| Geometric mean titer ratio of individual HAI Ab titer ratios Day 22/Day 01, Day 43/Day 01, Day 202/Day 43 | Day 01, Day 22, Day 43, Day 202 | Individual HAI Ab titer ratios are calculated for the following time points: Day 22/Day 01, Day 43/Day 01 and Day 202/Day 43 |
| Number of participants with individual HAI Ab titer ≥ 40 (1/dil) on Day 01, Day 22, Day 43, Day 202 | Day 01, Day 22, Day 43, Day 202 | Influenza vaccine antibody titers are measured by HAI assay |
| Number of participants with seroconversion on Day 22 compared to Day 01 (baseline) | Day 01, Day 22 | Seroconversion is defined as titer \< 10 (1/dil) on Day 01 and post-injection titer ≥ 40 (1/dil) on Day 22; or defined as titer ≥ 10 (1/dil) on Day 01 and a ≥ 4 fold increase in titer (1/dil) on Day 22 |
| Number of participants with detectable HAI Ab titer | Day 01, Day 22, Day 43, Day 202 | Detectable HAI Ab titer: a titer ≥ 10 (1/dil) |
| Geometric mean titer of neutralization (NT) Ab titer | Day 01, Day 22, Day 43, Day 202 | Influenza vaccine antibody titers are measured by serum neutralization (SN) assay |
| Geometric mean titer ratio of individual NT Ab titer ratio | Day 01, Day 22, Day 43, Day 202 | Individual NT Ab titer ratios are calculated for the following time points: Day 22/Day 01, Day 43/Day 01 and Day 202/Day 43 |
| Number of participants with NT Ab titer ≥ 20 (1/dil) | Day 01, Day 43, Day 202 | NT Ab titer ≥ 20 (1/dil) on Day 43; compared to Day 01 and Day 202 |
| Number of participants with NT Ab titer ≥ 40 (1/dil) | Day 01, Day 43, Day 202 | NT Ab titer ≥ 40 (1/dil) on Day 43; compared to Day 01 and Day 202 |
| Number of participants with NT Ab titer ≥ 80 (1/dil) | Day 01, Day 43, Day 202 | NT Ab titer ≥ 80 (1/dil) on Day 43; compared to Day 01 and Day 202 |
| Geometric mean fold-rise of fold increase in NT Ab titer [post/pre] ≥ 2 and ≥ 4 | Day 43 | Influenza vaccine antibody titers are measured by serum neutralization (SN) assay |
| Number of participants with detectable NT Ab titer | Day 01, Day 22, Day 43, Day 202 | Detectable NT Ab titer: a titer ≥ 10 (1/dil) on Day 01, Day 22, Day 43, Day 202 |
Countries
United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed