The Immunogenicity of Simultaneous Administration of Quadrivalent Influenza Vaccine and 23-valent Pneumococcal Vaccine

A Randomized, Open-label, Parallel Design Study to Compare the Immunogenicity of Simultaneous Administration Versus Sequential Administration of Quadrivalent Influenza Vaccine and 23-valent Pneumococcal Vaccine

The immunogenicity of simultaneous administration of quadrivalent influenza vaccine and pneumococcal vaccine was unknown. The purpose of present study is to compare the immunogenicity of simultaneous administration of influenza vaccine and pneumococcal vaccine with that of separate administration.

Study Overview

• Status: Completed
• Conditions: Influenza; Pneumococcal Pneumonia
• Intervention / Treatment: Biological: Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®; Biological: Sequential administration of Pneumovax NP® and Fluvic HA syringe®

Detailed Description

The immunogenicity of simultaneous administration of quadrivalent influenza vaccine and pneumococcal vaccine was unknown. We compare the immunogenicity of simultaneous administration of quadrivalent influenza vaccine and pneumococcal vaccine with that of separate administration.

162 Participants are randomly assigned to one of the two study groups; Simultaneous administration group: receive injections of pneumococcal vaccine and influenza vaccine simultaneously.

Sequential administration group: receive injections of pneumococcal vaccine 2 weeks after the injection of the influenza vaccine.

We compare the immunogenicity of the two groups.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kamogawa, Chiba, Japan, 2968602
      • Department of Pulmonary Medicine, Kameda Medical Center

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:

• adults aged ≧65 years who had never received pneumococcal vaccine and quadrivalent influenza vaccine of 2015/2016 season

Exclusion Criteria:

• a sensitivity to pneumococcal and influenza vaccine
• received other inactivated vaccine within 14 days
• received other live vaccine within 28 days
• the presence of conditions known to impair pneumococcal vaccine response
• having malignant disease
• taking oral corticosteroids or immunosuppressive agent
• history of splenectomy
• history of an acute febrile illness or signs of severe acute illness at the time of vaccination
• other inappropriate condition to receive vaccination
• suffering an acute illness requiring antibiotics or steroids within the past month
• not expected to survive 12 months were also excluded

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Simultaneous administration group; The subjects receive injections of pneumococcal vaccine and influenza vaccine simultaneously. We use commercially available PPV23 (Pneumovax NP®, MSDKK, Tokyo, Japan) containing 25 μg each of 23 capsular polysaccharide types. We use Fluvic HA syringe® (Handai Biken Ltd, Osaka, Japan), quadrivalent influenza vaccine (0.5ml) of 2015/2016 season.	Biological: Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®; Injections of pneumococcal vaccine and influenza vaccine simultaneously.; Other Names: Pneumovax NP® and Fluvic HA syringe®
Active Comparator: Sequential administration group; The subjects receive injections of pneumococcal vaccine 2 weeks after the injection of the influenza vaccine. We use commercially available PPV23 (Pneumovax NP®, MSDKK, Tokyo, Japan) containing 25 μg each of 23 capsular polysaccharide types. We use Fluvic HA syringe® (Handai Biken Ltd, Osaka, Japan), quadrivalent influenza vaccine (0.5ml) of 2015/2016.	Biological: Sequential administration of Pneumovax NP® and Fluvic HA syringe®; Injections of pneumococcal vaccine 2 weeks after the injection of the influenza vaccine.; Other Names: Pneumovax NP® and Fluvic HA syringe®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Positive Antibody Response in Serotype 23F of Pneumococcal Antibody.	The primary endpoint was the number of patients with positive antibody responses (≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination) in serotype 23F of the pneumococcal antibody.	1month after the dose of PPV23

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Positive Antibody Response in Serotype 3, 4, 6B, 1 4 and 19A of Pneumococcal Antibody.	Positive antibody response was defined as ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination in respective serotypes of the pneumococcal antibody.	4 to 6 weeks after vaccination (P1), 24 weeks to 27 weeks after vaccination (P2)
The Geometric Mean Concentrations of Specific Antibodies to the 6 Serotypes (23F, 3, 4, 6B 14 and 19A)	Pneumococcal IgG concentrations were converted using natural log transformations and presented as a geometric mean concentration.	Before vaccination (at baseline; in designated P0), 4 to 6 weeks after vaccination (P1), 24 weeks to 27 weeks after vaccination (P2)
The Number of Patients With Seroprotection Rate in Quadrivalent Influenza Vaccine.	Seroprotection rates (post-vaccination titer ≥1:40) were calculated to assess the immunogenicity of influenza vaccination.	4 to 6 weeks after vaccination (I1) and 24 weeks to 27 weeks after vaccination (I2)

Collaborators and Investigators

• Sponsor: Kameda Medical Center
• Collaborators: Merck Sharp & Dohme LLC; PPD; Osaka University
• Investigators: Principal Investigator: Kei Nakashima, MD, Department of Pulmonary Medicine, Kameda Medical Center

Publications and helpful links

General Publications

• Walter ND, Taylor TH, Shay DK, Thompson WW, Brammer L, Dowell SF, Moore MR; Active Bacterial Core Surveillance Team. Influenza circulation and the burden of invasive pneumococcal pneumonia during a non-pandemic period in the United States. Clin Infect Dis. 2010 Jan 15;50(2):175-83. doi: 10.1086/649208.
• Oishi K, Yoshimine H, Watanabe H, Watanabe K, Tanimura S, Kawakami K, Iwagaki A, Nagai H, Goto H, Kudoh S, Kuriyama T, Fukuchi Y, Matsushima T, Shimada K, Matsumoto K, Nagatake T. Drug-resistant genes and serotypes of pneumococcal strains of community-acquired pneumonia among adults in Japan. Respirology. 2006 Jul;11(4):429-36. doi: 10.1111/j.1440-1843.2006.00867.x.
• Hirst GK. THE QUANTITATIVE DETERMINATION OF INFLUENZA VIRUS AND ANTIBODIES BY MEANS OF RED CELL AGGLUTINATION. J Exp Med. 1942 Jan 1;75(1):49-64. doi: 10.1084/jem.75.1.49.
• Dransfield MT, Nahm MH, Han MK, Harnden S, Criner GJ, Martinez FJ, Scanlon PD, Woodruff PG, Washko GR, Connett JE, Anthonisen NR, Bailey WC; COPD Clinical Research Network. Superior immune response to protein-conjugate versus free pneumococcal polysaccharide vaccine in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009 Sep 15;180(6):499-505. doi: 10.1164/rccm.200903-0488OC. Epub 2009 Jun 25.
• Grabowska K, Hogberg L, Penttinen P, Svensson A, Ekdahl K. Occurrence of invasive pneumococcal disease and number of excess cases due to influenza. BMC Infect Dis. 2006 Mar 20;6:58. doi: 10.1186/1471-2334-6-58.
• Nakashima K, Aoshima M, Ohfuji S, Yamawaki S, Nemoto M, Hasegawa S, Noma S, Misawa M, Hosokawa N, Yaegashi M, Otsuka Y. Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial. Hum Vaccin Immunother. 2018;14(8):1923-1930. doi: 10.1080/21645515.2018.1455476. Epub 2018 May 14.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 28, 2015
• First Submitted That Met QC Criteria: October 29, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: quadrivalent influenza vaccine; immunogenicity; 23-valent pneumococcal vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Orthomyxoviridae Infections; Pneumococcal Infections; Pneumonia, Pneumococcal; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 15-041-160127