| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Two doses vaccination in elderly subjects aged between 65 and 85 years old, in good general health and not previously immunized with the 23-valent pneumococcal polysaccharide vaccine (Pneumo 23). |
|
| MedDRA Classification |
| 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 |
• To assess in healthy elderly subjects the safety and reactogenicity of the 11PCV adjuvanted either with AS01B or AS01E or AS02V, and of the 10-valent pneumococcal conjugate vaccine adjuvanted with AlPO4 (10PCV/AlPO4), given as a 2-dose vaccination 3 months apart, and of the licensed 23-valent pneumococcal polysaccharide vaccine (23PPV) given as a 1-dose vaccination.
• To compare the antibody response of the 11PCV, adjuvanted either with AS01B, AS01E or AS02V, after 1 and 2 injections with the antibody response of the 23PPV.
|
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety as measured by haematological and biochemical parameters in each group.
• To evaluate the humoral immune response elicited after 1 or 2 doses of 10PCV/AlPO4, injected at 3 months interval.
• To evaluate the humoral immune response at month 12 in each group.
• To evaluate the B-cell memory response to 4 polysaccharides in all subjects and to 11 polysaccharides in 10 subjects per group at Months 0, 1, 4 and 12.
• To evaluate the humoral immune response to carrier proteins at Months 0, 1, 3, 4 and 12, in the PCV groups.
• To evaluate the B-cell memory response to NTHi protein D at Months 0, 1, 4 and 12, in a subset of subjects (all subjects minus PS B-cell memory subset) of the PCV groups.
• To evaluate the T-cell response to NTHi protein D at Months 0, 1, 4 and 12, in a subset of subjects (all subjects minus PS B-cell memory subset) of the 11PCV/AS01B, 11PCV/AS01E, 11PCV/AS02V and 10PCV/AlPO4 groups.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
The cohort to be enrolled is a 23-valent pneumococcal polysaccharide vaccine naïve elderly subjects aged between 65 and 85 years old, in good general health at the time of the first vaccine dose.
All subjects must satisfy to the following criteria at study entry:
• Subjects who the investigator believes that they 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 between 65 and 85 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject.
|
|
| E.4 | Principal exclusion criteria |
• Previous vaccination against Streptococcus pneumoniae.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests, in particular:
Current or history of coronary artery disease or cardiac insufficiency
Uncontrolled hypertension
Clinically significant EKG abnormalities such as prior myocardial infarction, atrial fibrillation, heart block
Creatinin level ≥ 1.5 ULN
ALT-AST levels ≥ 1.5 ULN
Type 2 diabetes
Current or history of rheumatoid arthritis or temporal arteritis
Current acute or chronic active pulmonary pathology diagnosed on chest X-ray
• Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature <37.5°C or Axillary temperature <37.5°C.
• History of documented radiologically confirmed pneumonia within 3 years prior to first vaccination.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
• Current or history of Parkinson disease, Alzheimer disease, stroke, dementia or any serious neurologic or mental disorders .
• All malignancies (excluding non-melanic skin cancer) and lymphoproliferative disorders diagnosed or treated actively during the past 5 years.
• Subjects with documented anaemia or iron-deficiency (Hemoglobin level more than 10% below lower limit of normal)
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 3 months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
• Planned administration/ administration of a vaccine not foreseen by the study protocol within 2 weeks of the first dose of vaccine(s) with the exception of a Flu vaccine which can be administered at least 1 week preceding the first dose of vaccine(s) or 1 month after the first dose of the vaccine(s).
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Administration of immunoglobulins and/or any blood products within three months preceding the first dose of study vaccine or planned administration during the study period.
• History of administration of an experimental/licensed vaccine containing MPL or QS21.
• History of chronic alcohol consumption and/or drug abuse.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety and Reactogenicity
• Occurrence, intensity and relationship to vaccination of any solicited local and general signs and symptoms during a 7-day follow up period (i.e. day of vaccination and 6 subsequent days) after each vaccine dose.
• Occurrence, intensity and relationship to vaccination of unsolicited local and general signs and symptoms during a 31-day follow up period (i.e. day of vaccination and 30 subsequent days) after each vaccine dose.
• Occurrence and relationship to vaccination of all serious adverse events (SAEs) occurring throughout the study period.
Immunogenicity
• Post vaccination concentration IgG ≥ 5 ug/mL and fold increase Post/Pre ≥ 2 for at least 6 serotypes out of 11 (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F), one month after dose 2 for the 11PCV formulations, and one month after dose 1 for the 23PPV group.
• Post vaccination concentration IgG ≥ 5 ug/ml and fold increase Post/Pre ≥ 2 for at least 6 serotypes out of 11 (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F), one month after dose 1 for the 11PCV formulations and the 23PPV group.
|
|
| 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 | No |
| 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 | Information not present in EudraCT |
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
Print
