MF59-adjuvanted Influenza Vaccine and 23-valent Pneumococcal Polysaccharide Vaccine

Immunogenicity and Safety of MF59-adjuvanted Trivalent Influenza Vaccine (Fluad) and 23-valent Pneumococcal Polysaccharide Vaccine (PPV23) in the Elderly: Single Versus Concomitant Vaccination

Similar to children, adults frequently visit outpatient clinics to get two or more kinds of vaccines at the same time: pneumococcal vaccine, influenza vaccine, Td (diphtheria and tetanus) vaccine, HPV (human papilloma virus) vaccine, meningococcal vaccine, zoster vaccine, etc. This study is intended to evaluate the immunogenicity and safety of concomitant administration of 23-valent pneumococcal polysaccharide vaccine (PPV23, Prodiax) and MF59 adjuvanted trivalent influenza vaccine in the elderly subjects aged ≥65 years.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections; Influenza, Human
• Intervention / Treatment: Biological: Fluad alone; Biological: Fluad and PPV23 on the different arms; Biological: Fluad and PPV23 on the same arm; Biological: PPV23 alone

Detailed Description

During influenza season, concomitant influenza and pneumococcal vaccination would be an effective strategy to enhance pneumococcal vaccine coverage rate in high-risk adults. However, the immunogenicity and safety of concomitant vaccination need to be further investigated. There is data on immunogenicity and safety after concomitant administration of pneumococcal polysaccharide vaccine (PPV) and unadjuvanted influenza vaccine; no interference was noted between two vaccines. However, there are no data for MF59 adjuvanted influenza vaccine with pneumococcal vaccine. MF59 only locally reacts for immune response, so immunogenicity should be assessed for both vaccines injected in same arm versus different arms.

This study is intended to evaluate the immunogenicity and safety of concomitant MF59-adjuvanted trivalent influenza vaccine (MF59-aTIV, Fluad) and 23-valent pneumococcal polysaccharide vaccine (PPV23, Prodiax) vaccination in the elderly subjects aged ≥65 years. Healthy elderly subjects (N = 424) are randomized in a 1:1:1:1 ratio to receive MF59-aTIV alone (group 1), MF59-aTIV +PPV23 at different arm (group 2), MF59-aTIV +PPV23 at same arm (group 3) or PPV23 alone (group 4).

Hemagglutination inhibition (HI) assay and multiplex opsono-phagocytic killing assay (MOPA) will be used to compare the immunogenicity of each vaccine after single or concomitant vaccination at pre-vaccination and 1 month post-vaccination. MOPA will be taken for four serotypes (5, 6B, 18C and 19A).

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 65 years of age who are eligible for the study vaccines;
• Who have given written informed consent at the time of enrollment);
• Those who are available for all the visits scheduled in the study;
• Subjects In good health as determined by medical history, physical examination and clinical judgment of the investigator

Exclusion Criteria:

• History of egg allergy
• History of influenza vaccination in previous 6 months
• History of any pneumococcal vaccination
• Documented S. pneumonia infection in the previous 5 years
• Chemotherapy for malignancy within the past 30 days
• High-dose systemic steroid (prednisone ≥0.5 mg/kg/day) in the past 30 days
• Receipt of blood product within 6 months before enrollment
• Significant acute or chronic infection within the previous 7 days or fever within the previous day
• Any serious chronic or progressive disease
• Any condition that might interfere with the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fluad alone; 56 Fluad recipients: one vaccine injection administered on Day 0	Biological: Fluad alone; Fluad
Active Comparator: Fluad and PPV23 on the different arms; 56 concomitant Fluad-PPV23 recipients on the different arms: one dose of each vaccine administered on Day 0	Biological: Fluad and PPV23 on the different arms; Fluad and Prodiax
Active Comparator: Fluad and PPV23 on the same arm; 56 concomitant Fluad-PPV23 recipients on the same arm with 1 inch distance: one dose of each vaccine administered on Day 0	Biological: Fluad and PPV23 on the same arm; Fluad and Prodiax
Active Comparator: PPV23 alone; 56 PPV23 recipients: one vaccine injection administered on Day 0	Biological: PPV23 alone; Prodiax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion rates (A/H1N1, A/H3N2, and B)	a post-vaccination titer ≥1:40 in subjects with a pre-vaccination titer of <1:10 or a ≥4-fold titer increase in subjects with a pre-vaccination titer of ≥1:10	Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroprotection rates (A/H1N1, A/H3N2, and B)	Percentage of subjects with a post-vaccination titer ≥1:40	Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).
GMT folds (A/H1N1, A/H3N2, and B)	GMT-fold change: GMT ratio of the post-vaccination titer to pre-vaccination titer	Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination.
Opsonophagocytic assay (OPA) titers for four serotypes of PPV23 (serotypes 5, 6B, 18C and 19A)	OPA geometric mean titers for four PPV23 serotypes with corresponding 2-sided 95% confidence intervals will be compared between groups receiving PPV23: MF59-adjuvanted TIV + PPV23 at different arm, MF59-adjuvanted TIV + PPV23 at same arm and PPV23 alone.	Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Collaborators: Novartis
• Investigators: Principal Investigator: Hee Jin Cheong, MD, PhD, Korea University Guro Hospital; Study Director: Joon Young Song, MD, PhD, Korea University Guro Hospital

Publications and helpful links

General Publications

• Song JY, Cheong HJ, Tsai TF, Chang HA, Choi MJ, Jeon JH, Kang SH, Jeong EJ, Noh JY, Kim WJ. Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults. Vaccine. 2015 Aug 26;33(36):4647-52. doi: 10.1016/j.vaccine.2015.05.003. Epub 2015 May 14.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 22, 2014
• First Submitted That Met QC Criteria: August 22, 2014
• First Posted (Estimate): August 26, 2014

Study Record Updates

• Last Update Posted (Estimate): August 27, 2014
• Last Update Submitted That Met QC Criteria: August 26, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Orthomyxoviridae Infections; Pneumococcal Infections; Influenza, Human
• Other Study ID Numbers: FLUADPPV23