Immunogenicity and Safety of PCV13 and Fluad in Adults Aged ≥60 Years

Influenza Clinical Trial

Official title:

Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine (PCV13) and MF59-adjuvanted Influenza Vaccine (Fluad) After Concomitant Vaccination in Adults Aged ≥60 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02215863
• Other study ID #: FLUPCV13
• Status: Completed
• Phase: Phase 4
• First received: August 11, 2014
• Last updated: March 31, 2015
• Start date: September 2014
• Est. completion date: March 2015

Study information

• Verified date: March 2015
• Source: Korea University Guro Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Recent reviews have highlighted the unpredictability and complexity of immune interference when multivalent conjugate vaccines are co-administered with other pediatric vaccines. It has become evident that the likelihood of immune interference (in response to conjugated- or co-administered antigens) increases in proportional to the number of glyco-conjugates (valencies) and dosages of carrier proteins. There are many kinds of carrier proteins: tetanus toxoid (TT), diphtheria toxoid (DT), CRM197 (non-toxic variant of DT), OMP (complex outer-membrane protein mixture from Neisseria meningitidis) and non-typeable Hemophilus influenza-derived protein D. Among them, TT is a more potent inducer of T-helper immunity, but carrier-induced-epitopic suppression (dose-dependent carrier antibody and carrier B cell dominance) may occur with TT. In comparison, DT and CRM197 are weaker B-cell immunogens, but apparently trigger more T-regulatory mechanism. Recent pediatric studies of PCV13 co-administered with DTaP vaccines showed 6B GMT (geometric mean titer) to be somewhat reduced compared to the results with PCV13 alone.

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. PCV13 has limited co-administration information for adjuvanted influenza vaccine.

This study is designed to evaluate the immunogenicity and safety of PCV13 and MF59-adjuvanted influenza vaccine (Fluad) after concomitant administration in adults aged 60 years or older.

Description:

This study is a multi-centered, randomized controlled clinical trial: Korea University Guro Hospital, Korea University Ansan Hospital, Hallym University Gangnam Sacred Hospital and Catholic University Medical College, St. Vincent's Hospital.

The primary objective is to evaluate the immunogenicity of Fluad after concomitant administration of Fluad and PCV13 in adults aged 60 years or more. This study is designed to demonstrate non-inferiority of sero-conversion rate after Fluad vaccination: Fluad-PCV13 co-administration group versus Fluad alone group

The secondary objective is to evaluate the immunogenicity of PCV13 after concomitant administration in adults aged 60 years or more. This study is designed to demonstrate non-inferiority of PCV13 when co-administered with Fluad compared with PCV13 alone.

This study is also designed to evaluate the safety of concomitant PCV13-Fluad administration in adults aged 60 years or more. All the participants will be followed for the duration of an expected average of 4 weeks after vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1195
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Adults aged =60 years who signed the informed consent

Exclusion Criteria:

• Previous pneumococcal vaccine recipients

• Egg allergy

• History of serious adverse event after vaccination,

• any acute disease or infection

• History of neurological symptoms or signs

• Impairment of immune function or immunosuppressant use

• Bleeding diathesis

• Fever (defined as axillary temperature ³38.0°C) within 3 days (prior to Visit 1)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human
• Streptococcus Pneumoniae

Intervention

Biological:
• Fluad and Prevenar13

• Fluad

• Prevenar13

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Hallym University Gangnam Sacred Hospita	Seoul
Korea, Republic of	Catholic University Medical College, St. Vincent's Hospital	Suwon

Sponsors (2)

Lead Sponsor	Collaborator
Korea University Guro Hospital	Pfizer

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency and duration of local and systemic adverse events	The safety profiles of co-administration of Fluad and PCV13 will be compared to those of single vaccination.	All participants will be followed until 4 weeks after vaccination)	Yes
Primary	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)	No
Secondary	Seroprotection rates and GMT folds (A/H1N1, A/H3N2, and B)	Seroprotection rate: percentage of subjects with a post-vaccination titer =1:40; 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).	No
Secondary	Opsonophagocytic assay (OPA) titers for PCV13	OPA geometric mean titers for 13 PCV13 serotypes with corresponding 2-sided 95% confidence intervals between groups receiving PCV 13 and then compare the results	Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).	No