Clinical trial NCT02215863: Immunogenicity and Safety of PCV13 and Fluad in Adults Aged ≥60 Years
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Streptococcus Pneumoniae
Keywords: Immunogenicity, Safety, MF59, Influenza vaccine, Pneumococcal vaccine
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-08-13
Enrollment: 1195
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Seroconversion rates (A/H1N1, A/H3N2, and B)
timeFrame: Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination)
Secondary outcomes:
measure: Seroprotection rates and GMT folds (A/H1N1, A/H3N2, and B)
timeFrame: Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).
measure: Opsonophagocytic assay (OPA) titers for PCV13
timeFrame: Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination).
Other outcomes:
measure: Frequency and duration of local and systemic adverse events
timeFrame: All participants will be followed until 4 weeks after vaccination)
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University Gangnam Sacred Hospita
city: Suwon
country: Korea, Republic of
facility: Catholic University Medical College, St. Vincent's Hospital
Study officials:
affiliation: Korea University Guro Hospital
name: Hee Jin Cheong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Guro Hospital
name: Joon Young Song, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Song JY, Cheong HJ, Hyun HJ, Seo YB, Lee J, Wie SH, Choi MJ, Choi WS, Noh JY, Yun JW, Yun JG, Kim WJ. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine and an MF59-adjuvanted influenza vaccine after concomitant vaccination in ⩾60-year-old adults. Vaccine. 2017 Jan 5;35(2):313-320. doi: 10.1016/j.vaccine.2016.11.047. Epub 2016 Dec 3.