| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| The target population for this study is adults in stable health ≥ 50 years of age at risk for complications of influenza and pneumococcal diseases. |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10022005 |
| E.1.2 | Term | Influenza viral infections |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061353 |
| E.1.2 | Term | Pneumococcal infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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. |
|
| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. |
|
| E.4 | Principal 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 contraceptive precautions.
15) Any condition which, in the opinion of the investigator, prevents the subject from participating in the study or would make intramuscular (IM) injection unsafe.
16) Asplenia or dysfunction of the spleen. This excludes homozygous sickle cell disease or coeliac syndrome that may lead to splenic dysfunction.
17) 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.
18) History of chronic alcohol consumption and/or drug abuse.
19) History of Guillain-Barré syndrome.
20) A history of anaphylaxis following ANY vaccination. |
|
| E.5 End points |
| E.5.1 | 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. |
|
| E.5.1.1 | 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. |
|
| E.5.2 | 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. |
|
| E.5.2.1 | 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). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 7 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 8 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 8 |
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