Study of a Quadrivalent Influenza Vaccine Administered Intramuscularly in Children/Adolescents and Adults

Safety and Immunogenicity of a Quadrivalent Influenza Vaccine Administered Via the Intramuscular Route in Child/Adolescent and Adult Subjects

The aim of the study is to assess the safety profile of a quadrivalent influenza vaccine (QIV) and to demonstrate that 3 different industrial lots of QIV induce an equivalent immune response in children/adolescents (9 to 17 years of age) and adults (18 to 60 years of age).

Primary Objective:

• To describe the safety profile (injection site reactions and systemic events) of each vaccine during the 21 days following vaccination, and serious adverse events (including adverse events of special interest) throughout the study in all adult and child/adolescent participants.

Secondary Objectives:

• To demonstrate that the 3 different industrial lots of quadrivalent influenza vaccine (QIV) induce an equivalent immune response at 21 days post-vaccination in both age groups (lot consistency)
• To describe the compliance of the immunogenicity of QIV to the European Medicines Agency Note for Guidance (NfG) (CPMP/BWP/214/96) in each age group.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); Biological: 2011 to 2012 Trivalent Influenza Vaccine

Detailed Description

All participants will receive a single injection of their assigned vaccine during Visit 1. They will be followed up for safety and immunogenicity through Day 21 post-vaccination (Visit 2), and also monitored for safety for up to 6 months post-vaccination.

• Study Type: Interventional
• Enrollment (Actual): 1701
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
  • Westmead NSW, Australia, 2145
• Philippines
  • Calamba Laguna City, Philippines
  • Malate, Manila, Philippines
  • Muntinlupa City, Philippines, 1781
  • Quezon City, Philippines

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 9 to 11 years (children), 12 to 17 years (adolescents), or 18 to 60 years (adults) on the day of inclusion
• For child/adolescent subjects, informed consent form has been signed and dated by the parent(s) (and subject, if applicable by local regulations), or another legally acceptable representative (and independent witness, if required by local regulations), and the assent form has been signed and dated by the subject (if applicable by the local Ethics Committee or country regulations). For adult subjects, informed consent form has been signed and dated by the subject (and an independent witness, if required by local regulations).
• Subject/subject and parent/legally acceptable representative is/are able to attend all scheduled visits and to comply with all trial procedures
• Covered by health insurance, if required by local regulation.

Exclusion Criteria:

• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination)
• Participation at the time of study enrollment or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding trial vaccination or planned receipt of any vaccine in the 3 weeks following trial vaccination
• Previous vaccination against influenza with the 2012 Southern Hemisphere formulation or the 2011-2012 Northern Hemisphere formulation in the previous 6 months with either the trial vaccine or another vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
• Self-reported thrombocytopenia, contraindicating intramuscular vaccination based on investigator's judgment
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination based on investigator's judgment
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction (for adolescent and adult subjects)
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided
• Identified as an investigator or employee of the investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural, or adopted child) of the investigator or employee with direct involvement in the proposed study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: QIV Lot 1; Participants will receive the Quadrivalent Influenza Vaccine (QIV) from Lot 1.	Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); 0.5 mL, Intramuscular
Experimental: Group 2: QIV Lot 2; Participants will receive the Quadrivalent Influenza Vaccine (QIV) from Lot 2.	Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); 0.5 mL, Intramuscular
Experimental: Group 3: QIV Lot 3; Participants will receive the Quadrivalent Influenza Vaccine (QIV) from Lot 3.	Biological: Quadrivalent Influenza Vaccine (split virion, inactivated); 0.5 mL, Intramuscular
Active Comparator: Group 4: TIV; Participants will receive the Trivalent Influenza Vaccine (TIV).	Biological: 2011 to 2012 Trivalent Influenza Vaccine; 0.5 mL, Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants reporting solicited injection site reactions and solicited systemic reactions during the trial	Solicited Injection Site Reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited Systemic Reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Shivering	Day 0 to 7 post-vaccination
Percentage of participants reporting unsolicited systemic reactions including serious adverse events (SAE) throughout the trial.	An SAE is defined as any untoward medical occurrence that at any dose (including overdose): Results in death; Is life-threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability / incapacity; Is a congenital anomaly / birth defect; Is an important medical event.	Day 0 up to six months post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with seroprotection and seroconversion post vaccination with either the investigational QIV, or TIV or the licensed 2011-2012 TIV	Immunogenicity assessed by hemagglutination inhibition (HAI) assay for each vaccine strain. Seroprotection defined as a post-vaccination titer of ≥ 40 (1/dil); Seroconversion defined for participants with a pre-vaccination titer < 10 (1/dil) and a post-vaccination titer of ≥ 40 (1/dil).	Day 21 post-vaccination
Level of anti-hemagglutinin antibody titers for each of the 4 strains for each lot of the investigational QIV vaccine.		21 Days post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Cadorna-Carlos JB, Nolan T, Borja-Tabora CF, Santos J, Montalban MC, de Looze FJ, Eizenberg P, Hall S, Dupuy M, Hutagalung Y, Pepin S, Saville M. Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. Vaccine. 2015 May 15;33(21):2485-92. doi: 10.1016/j.vaccine.2015.03.065. Epub 2015 Apr 2.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: November 23, 2011
• First Submitted That Met QC Criteria: November 25, 2011
• First Posted (Estimate): November 29, 2011

Study Record Updates

• Last Update Posted (Estimate): March 29, 2013
• Last Update Submitted That Met QC Criteria: March 28, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Influenza; Trivalent Inactivated Influenza Vaccine; Quadrivalent Inactivated Influenza Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: GQM04; U1111-1122-2719 (Other Identifier: WHO); 2011-005101-79 (EudraCT Number)