A Phase 2, Randomized, Observer-Blind, Multicenter Study to Evaluate the Immunogenicity and Safety of Several Doses of Antigen and MF59 Adjuvant Content in a Monovalent H5N1 Pandemic Influenza Vaccine in Healthy Pediatric Subjects 6 Months to < 9 Years of Age

PHRR200428-002637

V87_30

2020-CT0528

A Phase 2, Randomized, Observer-Blind, Multicenter Study to Evaluate the Immunogenicity and Safety of Several Doses of Antigen and MF59 Adjuvant Content in a Monovalent H5N1 Pandemic Influenza Vaccine in Healthy Pediatric Subjects 6 Months to < 9 Years of Age

This randomized, observer blind, multi-center clinical trial evaluates the immunogenicity in healthy children 6 months to < 9 years of age utilizing 6 different aH5N1 vaccine formulations, in order to describe the possible impact of decreasing the quantities of antigen and/or adjuvant dosage on the antibody responses. In addition, levels of antibody persistence (at Day 202/ 6 months after vaccination) and the safety profile of each vaccine regimen will be assessed.
Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart. The vaccine regimens are:
A. Lowest-dose, less-adjuvanted vaccine = 1.875 μg H5N1 antigen + 0.125 mL MF59 adjuvant, with 2 consecutive administrations: dose 1 at Day 1 and dose 2 at Day 22
B. Low-dose, less-adjuvanted vaccine = 3.75 μg H5N1 antigen + 0.125 mL MF59 adjuvant, with 2 consecutive administrations: dose 1 at Day 1 and dose 2 at Day 22
C. Mid-dose, less-adjuvanted vaccine = 7.5 μg H5N1 antigen + 0.125 mL MF59 adjuvant, with 2 consecutive administrations: dose 1 at Day 1 and dose 2 at Day 22
D. Lowest-dose, adjuvanted vaccine = 1.875 μg H5N1 antigen + 0.25 mL MF59 adjuvant, with 2 consecutive administrations: dose 1 at Day 1 and dose 2 at Day 22
E. Low-dose, adjuvanted vaccine = 3.75 μg H5N1 antigen + 0.25 mL MF59 adjuvant, with 2 consecutive administrations: dose 1 at Day 1 and dose 2 at Day 22
F. Mid-dose, adjuvanted vaccine = 7.5 μg H5N1 antigen + 0.25 mL MF59 adjuvant, with 2 consecutive administrations: dose 1 at Day 1 and dose 2 at Day 22
Immunogenicity will be measured by HI and MN assays. Blood samples for serology assessments will be collected from each subject on Day 1 (before randomization), and Day 22 (before vaccination), Day 43, and Day 202.

Ongoing

H5N1 pandemic influenza

Primary Safety Objective:
To evaluate the safety in each study vaccine group from Day 1 through Day 387, by total population and by age cohort

Primary Immunogenicity Objective:
To assess by total population and by age cohort, the antibody responses to each of the study vaccines prior to (Day 1) and at 3 weeks after the first or second vaccination (Day 22 or Day 43), as measured by HI and MN assays

Secondary Immunogenicity Objective:
To evaluate in each study vaccine group, by total population and by age cohort, the persistence of antibody responses to the H5N1 vaccine strain 6 months after the second vaccination (Day 202) as measured by HI and MN assays

Completed

• Estonia
• Philippines

Clinical Trial

20200218121740

2020-04-15

0000-00-00

320

320

Not applicable

18 Feb 2021

Inclusion Criteria
1. Healthy male and female subjects of 6 months through 2. Documented consent provided by the subject's parent(s)/LAR(s) have voluntarily given written informed consent/assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Subject's parent(s)/LAR(s) able to comprehend and comply with all study procedures, and available for all clinical visits and telephone contacts scheduled in the study.
4. Subjects must provide a baseline blood sample within 10 days prior to the Day 1 vaccination.

Exclusion Criteria
1. Progressive, unstable or uncontrolled clinical conditions.
2. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
3. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws i.e.
    a. Subjects who have had a fever (body temperature measurement ≥ 38℃) within three days prior to vaccination. The subject may return for vaccination after they have been free of fever for three days.
    b. History of epilepsy or convulsions (excluding febrile convulsions).
    c. A subject who has any medical condition meeting the definition of AESI defined for the purposes of this trial
    d. Subjects who have received antipyretic medication within the past 24 hours prior to vaccination. The subject may return for vaccination after a period of 24 hours has passed since the administration of an antipyretic.
4. Abnormal function of the immune system resulting from:
    a. Clinical conditions.
    b. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent/assent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted
    c. Administration of antineoplastic and immunomodulating agents or radiotherapy from within 90 days prior to informed consent/assent.
5. Suspicion of pandemic infuenza illness within past six months or have ever received previous pandemic H5N1 flu vaccination.
6. Received immunoglobulins or any blood products within 180 days prior to informed consent/assent.
7. Received an investigational or non-registered medicinal within 30 days prior to informed consent/assent.
8. Children of study site staff (this includes research or clinic staff) or children who are otherwise related to study site staff or have household members who are study site staff. Study site staff are employees with direct or indirect contact with study subjects and or/have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, medical assistants, document scanners, etc. study personnel as an immediate family or household member.
9. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
10. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccine) prior to enrolment in this study or who are planning to receive any vaccine prior to day 43. Following day 43 other vaccines may be administered, including seasonal flu.

Interventional

H5N1 Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted)

H5N1 Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted)

Randomized

Single Blind

Observer-blind

Not Applicable

To assess the safety and immunogenicity in healthy Pediatric Subjects 6 Months to < 9 Years of Age of 6 different formulations including either 1.875, 3.75, or 7.5 µg HA of pandemic H5N1 influenza strain combined with either 0.125 mL or 0.25 mL MF59, in two IM injections administered three weeks apart.

Phase II