Clinical trial NCT02218697: Evaluation of the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine Influsplit™ Tetra (Fluarix™ Tetra) (GSK2321138A) When Co-administered With Pneumovax™ 23 in Adults 50 Years of Age and Older
Official title: Immunogenicity and Safety Study of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine 2014/2015 Influsplit™ Tetra (Fluarix™ Tetra) (GSK2321138A) When Co-administered With Pneumovax™ 23 in Adults 50 Years of Age and Older
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Immunogenicity
Influsplit Tetra (Fluarix Tetra) 2014/2015 season
Safety
Adults
Pneumovax 23/Pneumovax
Co-administration
Elderly
Seasonal influenza
Pneumococcal infection
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-08-18
Enrollment: 357
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to investigate the immunogenicity and safety when GSK Biologicals' influenza vaccine Influsplit™ Tetra (Fluarix™ Tetra) is co-administered with Merck \& Co. Inc.'s pneumococcal vaccine (Pneumovax™23/Pneumovax) in adults 50 years of age and older at risk for complications from influenza and pneumococcal infections.


Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
* A male or female aged 50 years or above at the time of the first vaccination at risk for complications from influenza and/or pneumococcal infections, meeting their respective countries' recommendations for vaccination against influenza and pneumococcal disease.

  * At risk subjects include adults with chronic respiratory, heart, kidney, liver or neurological disease; human immunodeficiency virus (HIV) disease on combination antiretroviral therapy (cART) with cluster of differentiation 4 (CD4) T-cell counts greater than 350 cells/mm3; sickle cell disease or coeliac syndrome that may lead to splenic dysfunction (all other asplenics are excluded). The decision to enrol should be based on the investigators clinical judgement.
* Written informed consent obtained from the subject.
* Female subjects of non-childbearing potential may be enrolled in the study.

  * Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Inhaled, topical and low-dose intra-articular steroids are allowed.
* Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose and 30 days after the last dose of vaccine.
* Administration of such a vaccine has to be documented in the "Concomitant vaccination" of the electronic Case Report Form (eCRF).
* Administration of long-acting immune-modifying drugs/treatment within six months prior to the first vaccine dose or expected administration at any time during the study period. These immunosuppressant drugs/treatment/Biologics include:

  * Methotrexate
  * Leflunomide
  * Azathioprine and 6-mercaptopurine
  * Cyclosporin A
  * Cyclophosphamide
  * Tacrolimus, everolimus, sirolimus, temsirolimus
  * Mycophenolate mofetil
  * Antilymfocytaire immunoglobulins
  * Tumor Necrosis Factor (TNF) inhibitors: Adalimumab (Humira®), certolizumab (Cimzia®), etanercept (Enbrel®), golimumab (Simponi®) and infliximab(Remicade®)
  * Monoclonal antibodies and other biologicals: Rituximab (Mabthera®), Abatacept (Orencia®), tocilizumab (RoActemra®), basiliximab (Simulect®), Natalizumab (Tysabri®) cluster of differentiation 3 (CD3), ...
  * Antitumor agents: alkylating agents, antimetabolites, antitumor antibiotics, topoisomerase inhibitors, microtubule inhibitors and other anti-tumor agents
  * Lenalidomide Revlimid®
  * Tasonermin: Beromun®
  * Proleukin® (aldesleukin; Novartis, ...)
  * Tyrosine kinase inhibitor (Glivec®)Omalizumab Xolair®
  * Eculizumab Soliris® The above list is compiled from: \[Federal Public Service Belgium: Health, Food Chain Safety and Environment\].
  * Any immunosuppressive treatment which in the opinion of the investigator will not allow an adequate immune response. Inhaled, topical and low-dose intra-articular steroids are allowed.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Previous vaccination with a pneumococcal vaccine within the last five years.
* Previous vaccination with an influenza vaccine within the last six months.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. HIV infected subjects on cART with CD4 T-cell counts above 350 cells/mm3 can be enrolled.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥ 38.0°C (100.4°F). The preferred route for recording temperature in this study will be axillary.
  * Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever \[≥ 38.0°C (100.4°F)\] may be enrolled at the discretion of the investigator.
* Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* Any condition which, in the opinion of the investigator, prevents the subject from participating in the study or would make intramuscular (IM) injection unsafe.
* Asplenia or dysfunction of the spleen. This excludes homozygous sickle cell disease or coeliac syndrome that may lead to splenic dysfunction.
* Acute clinically significant (i.e. a medically significant change from baseline condition in the past 30 days) pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* History of chronic alcohol consumption and/or drug abuse.
* History of Guillain-Barré syndrome.
* A history of anaphylaxis following ANY vaccination.

Primary outcomes:
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies Titers Against the 4 Vaccine Strains.
timeFrame: At Day 28 post Influsplit™ Tetra vaccination
measure: Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 6 Pneumococcal Serotypes (1, 3, 4, 7F, 14 and 19A).
timeFrame: At 28 days after Pneumovax™ 23 vaccination
Secondary outcomes:
measure: Number of Subjects Reporting Solicited Local Adverse Events (AEs)
timeFrame: Within 7 days (Days 0 - 6) after each dose and across doses.
measure: Number of Subjects Reporting Solicited General Adverse Events (AEs)
timeFrame: Within 7 days (Days 0 - 6) after each dose and across doses.
measure: Duration of Local Adverse Events
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited General AEs.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Reporting the Occurrence of Medically Attended Adverse Events (MAEs)
timeFrame: Throughout the study period (Days 0-180)
measure: Number of Subjects Reporting the Occurrence of Potential Immune Mediated Diseases (pIMDs)
timeFrame: During the entire study period (Days 0-180)
measure: Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
timeFrame: Within the 28-day (Days 0-27) post-vaccination period
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: Throughout the study period (Days 0-180)
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Influenza Vaccine Strains
timeFrame: At Day 0 and Day 28
measure: Number of Subjects Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 0 and Day 28
measure: Number of Seroconverted Subjects for Anti-Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 28
measure: Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 28
measure: Number of Subjects With Anti-pneumococcal Antibody Concentrations for the Following Serotypes: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F
timeFrame: At Days 0 (Co-Ad group only), 28 (both groups), and 56 (Control group only)
measure: Pneumococcal Vaccine Response in Terms of Anti-pneumococcal Antibody Concentrations Against 12 Pneumococcal Serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F)
timeFrame: At Days 0 (Co-Ad group only), 28 (both groups), and 56 (Control group only)
measure: Number of Subjects Whose N Antibody Titers Were at Least 2 or 4-fold Higher Than Their Pre-vaccination Titer by Anti-pneumococcal Serotype Subjects.
timeFrame: At 28 days post-vaccination with Pneumovax™ 23
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Angers
country: France
facility: GSK Investigational Site
city: Laval
country: France
facility: GSK Investigational Site
city: Nantes cedex 2
country: France
facility: GSK Investigational Site
city: Saint Cyr sur Loire
country: France
facility: GSK Investigational Site
city: Tours
country: France
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ofori-Anyinam O, Leroux-Roels G, Drame M, Aerssens A, Maes C, Amanullah A, Schuind A, Li P, Jain VK, Innis BL. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine co-administered with a 23-valent pneumococcal polysaccharide vaccine versus separate administration, in adults >/=50years of age: Results from a phase III, randomized, non-inferiority trial. Vaccine. 2017 Nov 1;35(46):6321-6328. doi: 10.1016/j.vaccine.2017.09.012. Epub 2017 Oct 5.