Pneumococcal PneumoniaPhase 4NCT02592486

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

A Phase 4 study testing Simultaneous administration of Pneumovax NP® and Fluvic HA syringe® and Sequential administration of Pneumovax NP® and Fluvic HA syringe® in people with Pneumococcal Pneumonia and Influenza, run by Kameda Medical Center at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 65 years and older
Conditions the study is for: Pneumococcal Pneumonia, Influenza
What is being tested?: Simultaneous administration of Pneumovax NP® and Fluvic HA syringe® and Sequential administration of Pneumovax NP® and Fluvic HA syringe®
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 162 participants
Where: 1 siteJapan
Study dates: Nov 2015to Aug 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 years and older
All sexes
No healthy volunteers
Older adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

1 site in 1 country.

Japan1 site

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

Other trials in Japan

About this study

Official title: 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

Read the 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.

Conditions: Pneumococcal Pneumonia, Influenza
Being tested: Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®, Sequential administration of Pneumovax NP® and Fluvic HA syringe®
Keywords: quadrivalent influenza vaccine, 23-valent pneumococcal vaccine, immunogenicity
Medical subject headings: Pneumonia, Pneumococcal, Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®Biological
Also called Pneumovax NP® and Fluvic HA syringe®
Injections of pneumococcal vaccine and influenza vaccine simultaneously.
Sequential administration of Pneumovax NP® and Fluvic HA syringe®Biological
Also called Pneumovax NP® and Fluvic HA syringe®
Injections of pneumococcal vaccine 2 weeks after the injection of the influenza vaccine.

Study groups in NCT02592486
Study group	Role	What they receive
Simultaneous administration group	Active comparator	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. Receives: Biological: Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®
Sequential administration group	Active comparator	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. Receives: Biological: Sequential administration of Pneumovax NP® and Fluvic HA syringe®

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1month after the dose of PPV23

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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.
Measured: 4 to 6 weeks after vaccination (I1) and 24 weeks to 27 weeks after vaccination (I2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2015Aug 2016

First posted30 Oct 2015 (estimated)
Study startNov 2015
Primary completionMar 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Pneumococcal PneumoniaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 162 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02592486
Sponsor's protocol ID: 15-041-160127
Status last verified: Aug 2018
First submitted: 28 Oct 2015
Last updated: 31 Jan 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 20014948
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.
PubMed 16771912
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.
PubMed 19871167
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.
PubMed 19556517
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.
PubMed 16549029
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.
PubMed 29561248

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pneumococcal Pneumonia trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02592486
Acronym / sponsor ID: 15-041-160127
Conditions: Pneumococcal Pneumonia, Influenza
Keywords: quadrivalent influenza vaccine, 23-valent pneumococcal vaccine, immunogenicity
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 162 participants (actual)
Lead sponsor: Kameda Medical CenterUniversity, hospital or other
Collaborators: PPD Development, LP, Osaka University, Merck Sharp & Dohme LLC
Study start: Nov 2015
Primary completion: Mar 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 30 Oct 2015 (estimated)
Results: Posted 31 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Simultaneous administration group	Active comparator	Biological: Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®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.
Sequential administration group	Active comparator	Biological: Sequential administration of Pneumovax NP® and Fluvic HA syringe®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.

Who may qualify

Ages: 65 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Simultaneous administration of Pneumovax NP® and Fluvic HA syringe®Also: Pneumovax NP® and Fluvic HA syringe®Injections of pneumococcal vaccine and influenza vaccine simultaneously.	Biological	Simultaneous administration group
Sequential administration of Pneumovax NP® and Fluvic HA syringe®Also: Pneumovax NP® and Fluvic HA syringe®Injections of pneumococcal vaccine 2 weeks after the injection of the influenza vaccine.	Biological	Sequential administration group

Primary outcome

The Number of Patients With Positive Antibody Response in Serotype 23F of Pneumococcal Antibody.
Time frame: 1month after the dose of PPV23
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.

3 secondary outcomes

The Number of Patients With Positive Antibody Response in Serotype 3, 4, 6B, 1 4 and 19A of Pneumococcal Antibody.
Time frame: 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)
Time frame: 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.
Time frame: 4 to 6 weeks after vaccination (I1) and 24 weeks to 27 weeks after vaccination (I2)

Results and safety

Results posted to the registry on 31 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Simultaneous Administration Group	81	81
Sequential Administration Group	81	76

Primary outcome: The Number of Patients With Positive Antibody Response in Serotype 23F of Pneumococcal Antibody.

Time frame: 1month after the dose of PPV23. Count of participants. Unit: Participants

Measure	Simultaneous Administration Group n = 81	Sequential Administration Group n = 76
Value	63	59

Population analysed: In the sequential group, 5 patients were excluded from primary analysis because of the reasons below. 1 patient: eligibility error, 1 patient: lost to follow-up (patient's decision), 3 patient: discontinued intervention (1 patient: fever, 2 patients: patient's decision

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Local reactions at the injection site as well as systemic reactions were monitored for 28 days in the group that received the simultaneous administration, and for 14 days after each injection in the sequential group.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Simultaneous Administration Group	0 of 81 (0%)	20 of 81 (24.7%)	Not reported
Sequential Administration Group	0 of 80 (0%)	31 of 79 (39.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 20014948Walter 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.
Background: PubMed 16771912Oishi 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.
Background: PubMed 19871167Hirst 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.
Background: PubMed 19556517Dransfield 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.
Background: PubMed 16549029Grabowska 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.
Derived from this study: PubMed 29561248Nakashima 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.

Related trials for Pneumococcal Pneumonia

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Active, not recruitingPhase 1
Trial to Evaluate Safety and Immune Response of an Investigational Pneumococcal Vaccine in Adults Aged 50 To 64 Years
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Active, not recruitingObservational study
A Study to Learn How Effective is PCV20 to Help Stop Adults Who Have a Higher Chance of Getting Pneumonia
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RecruitingPhase 4
Opportunistic Pneumococcal Immunisation Trial in MALnutrition
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kei Nakashima, MD principal investigator

Department of Pulmonary Medicine, Kameda Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Number of Patients With Positive Antibody Response in Serotype 23F of Pneumococcal Antibody. (time frame: 1month after the dose of PPV23). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02592486, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2019.