A Phase III, Randomized, Observer-blind, Multicenter Study to Evaluate the Efficacy, Immunogenicity and Safety of Seqirus’ Cell-Based Quadrivalent Subunit Influenza Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine or Placebo when Administrated in Healthy Subjects aged 6 Months through 47 Months

PHRR190125-002058

V130_14

2018-CT0460

A Phase III, Randomized, Observer-blind, Multicenter Study to Evaluate the Efficacy, Immunogenicity and Safety of Seqirus’ Cell-Based Quadrivalent Subunit Influenza Virus Vaccine (QIVc) Compared to a Non-Influenza Vaccine or Placebo when Administrated in Healthy Subjects aged 6 Months through 47 Months

This multicenter phase III clinical study evaluates the efficacy, immunogenicity and safety of a cell-based quadrivalent subunit influenza virus-vaccine compared to noninfluenza vaccine or placebo in subjects between 6 months through 47 months of age. The study features an observer blind design, parallel groups and 1:1 randomization between QIVc and a non-influenza vaccine or placebo. Based on previous influenza vaccination history, subjects will receive either one or two doses of either QIVc or noninfluenza vaccine or placebo. The non-influenza vaccine is a vaccine that prevents Neisseria meningitides serogroup C-infections (MenC-vaccine) and the placebo vaccine is saline for injection. Countries that use the MenC-vaccine as comparator vaccine should have an official authorization or license to use the MenC-vaccine in their country. In these countries, subjects aged 6 through 11 months at enrollment, will receive a (booster) dose of the MenC-vaccine during a study completion visit. In countries that do not have an official authorization for use of the MenC-vaccine, the comparator is a saline for injection. The study has a treatment period and a follow-up period. For subjects with a previous influenza vaccination history, the treatment period begins at the time of vaccination and ends 28 days after vaccination and will consist of 2 clinical visits and one reminder call to complete the subject diary card. The follow up period begins 28 days after vaccination and ends at the time of study completion visit. For subjects without or unknown previous influenza vaccination history, the treatment period begins at the time of first vaccination and ends 28 days after the second vaccination and will consist of 3 clinical visits and two reminder calls to complete the subject diary card, one after each vaccination. The follow up period begins 28 days after second vaccination and ends at the time of study completion visit. All subjects, irrespective of previous influenza vaccination history, will receive 1 safety follow-up call 90 days after last vaccination during the follow up period and the follow-up period will conclude with a study completion visit (clinic visit or call). In countries, in the exceptional case where calls are not feasible, study site personnel may visit the subject’s home to inquire about signs and symptoms of illness in the subject. Safety data collection will include standard solicited adverse event reporting via subject diary card for 7 days after each vaccine administration, all unsolicited adverse events (AEs) for 28 days after each vaccine administration, and special AE categories (serious adverse event (SAE), new onset of chronic disease (NOCD), medically-attended AEs for 30 days after ILI onset) for the full duration of the study. Blood samples will be collected from a sub-set of subjects participating in each influenza season (maximum 222 per season), during two clinic visits prior to the first vaccination and 28 days after last vaccination. Immunogenicity analyses will be performed to characterize baseline titers, response to vaccination and to understand the observed efficacy for the study population. Throughout the study, unscheduled visits are planned for subjects who manifest influenza-like illness (ILI) symptoms during the influenza season. The subject’s parent or legally acceptable representative (LAR) or delegate is contacted weekly to capture ILI symptoms throughout the study. When ILI symptoms occur, the parent/LAR/delegate should complete the ILI booklet.

Ongoing

Influenza is an infectious disease caused by the influenza virus, an orthomyxovirus with two clinically relevant types (Type A and B). Influenza Type A/H1N1, A/H3N2, and Type B/Victoria and B/Yamagata strains have circulated and caused disease in humans on a global basis since 1977 (Fiore, 2010), with a high susceptibility to severe influenza in children (Izurieta, 2000) (Bourgeois, 2006). Children aged < 5 years, and particularly those < 2 years of age, are at high risk of infection and are a priority for annual seasonal influenza vaccination throughout the world (WHO, 2012) (AAP, 2016). With vaccination as the recommended method to prevent influenza, both childhood influenza disease burden and community viral transmission could be reduced (Mertz, 2016).

1) To demonstrate the absolute vaccine efficacy of QIVc versus a non-influenza vaccine or placebo to prevent at least one of the following: a) RT-PCR confirmed illness caused by any influenza Type A and/or Type B virus, regardless of antigenic match. b) Culture confirmed illness caused by influenza virus strains antigenically matched to the influenza strains selected for the seasonal influenza vaccine.

Objectives evaluating QIVc compared to a non-influenza vaccine or placebo: 2) Prevention of culture confirmed illness caused by influenza virus strains antigenically dissimilar to the influenza strains selected for the seasonal vaccine. 3) Prevention of culture confirmed illness caused by any Type A and/or Type B virus. 4) Prevention of RT-PCR confirmed moderate-to-severe influenza caused by any influenza Type A and/or Type B virus.

Pending

• Honduras
• Malaysia
• New Zealand
• Philippines
• Thailand
• Vietnam

Clinical Trial

20180911144700

2018-11-21

0000-00-00

320

Unspecified

Unspecified

01 May 2019

In order to participate in this study, all subjects must meet ALL of the inclusion criteria described.
1. Individuals of 6 through 47 months of age on the day of informed consent.
2. Individuals whose parent(s)/LAR have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Individuals who can comply with study procedures including follow-up.
4. Individuals in generally good health as per the Investigator’s medical judgement.
Prior to receipt of second study vaccination, subjects must be evaluated to confirm that they are eligible for subsequent vaccination. If subjects do not meet the criteria of the original inclusion criteria listed above, they should not receive additional vaccinations.
Each subject must not have:
1. Acute (severe) febrile illness (see Section 4.3 Criteria for Delay of Vaccination). Enrollment could be considered if the fever is absent for 72 hours.
2. History of any anaphylaxis, serious vaccine reactions or hypersensitivity, including allergic reactions, to any component of vaccine or medical equipment whose use is foreseen in this study.
3. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. These may include known bleeding disorders, or treatment with anticoagulants in the 3 weeks preceding vaccination. 
4. A known history of Guillain-Barré Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.
5. Abnormal function of the immune system resulting from clinical conditions, which include:
a. Known or suspected congenital or acquired immunodeficiency.
b. Systemic administration of corticosteroids (PO/IV/IM) at any dose for more than 14 days, within 90 days prior to informed consent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids is also permitted.
c. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
6. Received immunoglobulins or any blood products within 180 days prior to informed consent.
7. Received an investigational or non-registered medicinal product within 30 days prior to informed consent, or intend to participate in another clinical trial during the study.
8. Participated in this trial in a prior season or is discontinued after randomization in the current season.
9. Study personnel, family and household members of study personnel should not participate.
10. 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.
11. Received influenza vaccination or has had documented influenza disease in the last 6 months prior to informed consent.

Interventional

Flucelvax Quadrivalent/ Flucelvax Tetra vaccine

The Flucelvax Quadrivalent/ Flucelvax Tetra vaccine is a is a sterile, slightly opalescent suspension in phosphate buffered saline. The dose to be  dministrated (0.5 mL) is formulated to contain a total of 60 μg hemagglutinin (HA) per 0.5 mL dose in the recommended ratio of 15 μg HA of each of the four (4) influenza strains recommended by WHO for inclusion in the quadrivalent vaccine formulation for the influenza season corresponding to the season of conduct of study. Each dose of Flucelvax Quadrivalent/Flucelvax Tetra may contain residual amounts of MDCK cell protein (≤ 8.4 μg), protein other than HA (≤ 160 μg), MDCK cell DNA (≤ 10 ng), polysorbate 80 (≤ 1500 μg), cetyltrimethlyammonium bromide (≤ 18 μg), and β-propiolactone (< 0.5 μg), which are used in the manufacturing process. The 0.5 mL pre-filled syringes contain no preservative or antibiotics.

Randomized

Single Blind

The trial is designed as an observer-blind study. During the treatment period of the study designated and trained unblinded nurse(s), physician(s), or other qualified health care professional will be responsible for administering the study vaccines to the subjects. They will be instructed not to reveal the identity of the study vaccines either to the subject’s parent(s)/LAR/delegate or to the investigative site personnel (i.e., investigator and study nurse) involved in the monitoring of conduct of the trial, except in an emergency if unblinding in IRT is not possible. Vaccine administration should be shielded from the subject’s parent(s)/LAR(s) and blinded study personnel. The unblinded personnel should not be involved in data collection or data review such as safety assessments and/or collect study data after the vaccinations. Study vaccines will be assigned through an Interactive Response technology system.

Parallel

1. a. First occurrence of RT-PCR confirmed influenza, due to any influenza Type A and/or B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms.
1. b. First occurrence of culture confirmed influenza, due to influenza Type A and/or B virus antigenically matched by ferret antigenicity testing to the strains selected for the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms.

Phase III