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.

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2014-001118-24-BE
• Date of registration: 18/07/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: 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.
• Scientific title: A Phase III, placebo-controlled, observer-blind, randomised, multi-centre study to describe the immunogenicity and safety of GSK Biologicals’ Quadrivalent Split Virion Influenza Vaccine 2014/2015 Influsplit™ Tetra (Fluarix™ Tetra) (GSK2321138A) when co-administered with Merck & Co. Inc.’s 23-valent pneumococcal polysaccharide vaccine injected intramuscularly in adults 50 years of age and older at risk for complications from influenza and pneumococcal infections. - FLU D-QIV-010 PRI
• Date of first enrolment: 19/08/2014
• Target sample size: 356
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001118-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: observer-blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, France

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

Key inclusion & exclusion criteria

Inclusion criteria:
1) 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).
2) 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 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.
3) Written informed consent obtained from the subject.
4) 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.
5) 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 236
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
1) 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.
2) 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.
3) 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.
4) Administration of such a vaccine has to be documented in the "Concomitant vaccination" of the eCRF.
5) 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®) 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.
6) 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.
7) Previous vaccination with a pneumococcal vaccine within the last five years.
8) Previous vaccination with an influenza vaccine within the last six months.
9) 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.
10) History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
11) 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.
12) 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.
13) Pregnant or lactating female.
14) Female planning to become pregnant or planning to discontinue

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

The target population for this study is adults in stable health = 50 years of age at risk for complications of influenza and pneumococcal diseases.
MedDRA version: 17.0 Level: HLT Classification code 10022005 Term: Influenza viral infections System Organ Class: 10021881 - Infections and infestations
MedDRA version: 17.0 Level: PT Classification code 10061353 Term: Pneumococcal infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Trade Name: Alpharix Tetra (Fluarix Tetra)
Product Name: Alpharix Tetra
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: ANTIGENS OF THE INFLUENZA VIRUS A/CALIFORNIA/7/2009 (H1N1)-LIKE VIRUS PDM09
Other descriptive name: ANTIGENS OF THE INFLUENZA VIRUS A/CALIFORNIA/7/2009 (H1N1)-LIKE VIRUS PDM09
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 30-
INN or Proposed INN: Antigens of the Influenza Virus A/Texas/50/2012 (H3N2)-Like Virus
Other descriptive name: Antigens of the Influenza Virus A/Texas/50/2012 (H3N2)-Like Virus
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 30-
INN or Proposed INN: Antigens of the Influenza Virus B/Massachusetts/02/2012-like virus
Other descriptive name: Antigens of the Influenza Virus B/Massachusetts/02/2012-like virus
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 30-
INN or Proposed INN: ANTIGENS OF THE INFLUENZA VIRUS B/BRISBANE/60/2008-LIKE VIRUS
Other descriptive name: ANTIGENS OF THE INFLUENZA VIRUS B/BRISBANE/60/2008-LIKE VIRUS
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Trade Name: Pneumovax™ 23/Pneumovax™
Product Name: Pneumovax™ 23/Pneumovax™
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 2
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 2
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3
Other descriptive name: PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 2

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) Humoral immune response: at Day 28 after D-QIV vaccination.
2) Anti-pneumococcal antibody concentrations: At 28 days after pneumococcal (PPV23) vaccination.

Main Objective: 1) To demonstrate the non-inferiority of the immune response to D-QIV (FLU D-QIV) in terms of HI antibody titres at Day 28 after D-QIV vaccination, for each influenza virus strain, when co-administered with or administered separately from PPV23 (Pneumovax 23).
2) To demonstrate the non-inferiority of the humoral immune response to PPV23 in terms of anti-pneumococcal antibody concentrations at 28 days after administration of the pneumococcal vaccine, for six pneumococcal serotypes (1, 3, 4, 7F, 14, 19A) , when co administered with or administered separately from D-QIV.

Primary end point(s): 1) Humoral immune response to each strain. HI antibody titres against each influenza virus strain post-vaccination with D-QIV.
- GMT ratios of the Control group (D-QIV+PBO/PPV23) over the Co-Ad group (D-QIV+PPV23/PBO) after D-QIV vaccination.
2) Anti-pneumococcal antibody concentrations against six pneumococcal serotypes (1, 3, 4, 7F, 14, 19A) post-vaccination with PPV23.
- GMC ratios of the Control group (D-QIV+PBO/PPV23) over the Co-Ad group (D-QIV+PPV23/PBO) group after PPV23 vaccination.

Secondary Objective: 1) To describe the reactogenicity and safety of D-QIV and PPV23 when given separately or when co-administered in terms of solicited adverse events (AEs), unsolicited AEs, medically attended adverse events (MAEs), potential immune-mediated diseases (pIMDs) and serious adverse events (SAEs)
2) To describe the immunogenicity of D-QIV when given separately or when co-administered with PPV23 in terms of GMT, seroconversion rate (SCR), seroprotection rate (SPR) and mean geometric increase (MGI).
3) To describe the immunogenicity of PPV23 when given separately or when co-administered with D-QIV in terms of anti-pneumococcal antibody concentrations for the serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) Solicited local and general symptoms: within 7 days (Days 0- 6) after each vaccination.
2) Unsolicited AEs: within 28 days (Days 0 – 27) after each vaccination.
3) SAEs: throughout the study period (Days 0-180).
4) MAEs and pIMDs: throughout the study period (Days 0-180).
5) Humoral immune response: at Day 0 and Day 28.
6) Humoral immune response: at Day 28.
7) Anti-pneumococcal antibody concentrations: Days 0 (Co-Ad group only), 28 (both groups), and 56 (Control group only).

Secondary end point(s): 1) Occurrence of solicited local and general symptoms.
- Occurrence, duration and intensity of each solicited local symptom after each vaccination
- Occurrence, duration, intensity and relationship to vaccination of each solicited general symptom after each vaccination
2) Occurrence of unsolicited AEs.
- Occurrence, intensity and relationship to vaccination of unsolicited AEs after each vaccination, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification.
3) Occurrence of SAEs.
- Occurrence and relationship to vaccination of all SAEs.
4) Occurrence of MAEs and pIMDs.
-Occurrence and relationship to vaccination of MAEs and pIMDs.
5) Humoral immune response to each strain. HI antibody titres against each influenza virus strain.
- Seropositivity rates and GMTs
- SPR
6) Humoral immune response to each strain. HI antibody titres against each influenza virus strain.
- SCR
- MGI
7) Anti-pneumococcal antibody concentrations for the following serotypes as determined by ELISA: 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.
- GMCs.
- Proportion of subjects with concentrations = 0.15 and = 0.35 µg/mL.
- Fold antibody concentration increases post-vaccination/pre-vaccination = 2 and = 4.

Secondary ID(s)

117276

Source(s) of Monetary Support

GlaxoSmithKline Biologicals