E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active immunization of infants for the prevention of any lower respiratory tract infections (LRTI; bronchiolitis and [broncho] pneumonia) associated with respiratory syncytial virus (RSV). |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory tract infection caused by respiratory syncytial virus (RSV) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 evaluate the safety and reactogenicity of the RSV investigational vaccine when administered intramuscularly (IM) as one (1.5x10^10 viral particles [vp]) dose or as two (5x10^10 vp) doses according to a 0, 1-month schedule, up to 60 days after Dose 1 (i.e., Day 61) in infants aged 6 and 7 months. |
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E.2.2 | Secondary objectives of the trial |
To evaluate RSV respiratory tract infections of any severity from Visit 1 through end of first RSV transmission season, in infants (6 and 7 months); To evaluate the safety of the RSV investigational vaccine administered IM as 1 (1.5x10^10 vp) or 2 (5x10^10 vp) doses by a 0, 1-month schedule from study start to the end of the second RSV transmission season in infants (6 and 7 months); To evaluate RSV respiratory tract infections from Visit 1 to the end of the second RSV transmission season, in infants (6 and 7 months); To evaluate very severe RSV-LRTI from Visit 1 to the end of the first RSV transmission season in RSV infected infants (6 and 7 months) with negative RSV exposure status; To evaluate humoral immunogenicity induced by the RSV investigational vaccine administered IM as 1 (1.5x10^10 vp) or 2 (5x10^10 vp) doses by a 0, 1-month schedule, from study start to the end of the first RSV transmission season in infants (6 and 7 months). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subjects' parent(s)/Legally Acceptable Representative [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol
•Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
•A male or female between and including 6 and 7 months of age (from the day the infant becomes 6 months of age until the day before the infant achieves 8 months of age) at the time of the first vaccination.
•Healthy subjects as established by medical history and clinical examination before entering into the study.
•Born full-term with a minimum birth weight of 2.5 kg.
•Subjects' parent(s)/LAR(s) need to have access to a consistent mean of telephone contact or computer. |
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E.4 | Principal exclusion criteria |
•Child in care
•Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 1), or planned use during the study period.
•Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean prednisone ≥ 0.5 mg/kg/day (for pediatric subjects), or equivalent. Topical steroids are allowed.
•Administration of long-acting immune-modifying drugs or planned administration at any time during the study period.
•Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
•Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine administration, with the exception of scheduled routine pediatric vaccines. Scheduled routine pediatric vaccines may be administered ≥ 7 days before a dose of study vaccine or ≥ 7 days following a dose of study vaccine, with the exception of live viral vaccines which may be administered ≥ 14 days before a dose or ≥ 7 days after a dose.
•Acute or chronic, clinically significant pulmonary, cardio-vascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
•A history of, or on-going confirmed RSV disease or highly compatible clinical picture.
•Serious chronic illness.
•Major congenital defects.
•History of any neurological disorders or seizures.
•History of or current autoimmune disease.
•History of recurrent wheezing. ("Recurrent wheezing" is defined as ≥ 2 episodes of wheezing in the subject´s lifetime). Wheezing should
have been verified on auscultation by doctor.
•History of chronic cough.
•Previous hospitalization for lower respiratory illnesses.
•Previous, current or planned administration of Synagis (palivizumab).
•Neurological complications following any prior vaccination.
•Born to a mother known or suspected to be Human Immmunodeficiency Virus (HIV)-positive.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination .
•Family history of congenital or hereditary immunodeficiency.
•Previous vaccination with a recombinant simian or human adenoviral vaccine.
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
•History of any reaction or hypersensitivity to any component of the
vaccines (investigational or control) or placebo used in this study or
any contraindication to them.
•Hypersensitivity to latex.
•Current severe eczema.
•Acute disease and/or fever at the time of enrolment (Visit 1).
•Any clinically significant Grade 1 or any ≥Grade 2 hematological or biochemical laboratory abnormality detected at the last screening blood sampling.
•Any medical condition that in the judgment of the investigator would make IM injection unsafe.
•Any other conditions that the investigator judges may interfere with study procedures, findings.
•Any conditions that could constitute a risk for the subjects while participating to this study.
•Weight below the fifth percentile according to the World Health
Organisation (WHO) weight-for-age tables.
•Concurrently participating in another clinical study, at any time during the study period, in which the subject or mother (if breastfeeding) has been or will be exposed to an investigational or a non-investigational vaccine/product.
•Planned move to a location that will prohibit participating in the trial until study end.
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of subjects with any solicited local adverse events;
Number of subjects with any solicited general adverse events;
Number of subjects with any unsolicited adverse events (AEs);
Number of subjects with any serious adverse events (SAEs);
Number of subjects with any AEs of specific interest |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During a 7-day follow-up period after each vaccination (i.e., the day of vaccination and 6 subsequent days);
During a 7-day follow-up period after each vaccination (i.e., the day of vaccination and 6 subsequent days);
During a 30-day follow-up period after each vaccination (i.e., the day of vaccination and 29 subsequent days);
From Day 1 up to Day 61;
During a 30-day follow-up period after each vaccination (i.e., the day of vaccination and 29 subsequent days). |
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E.5.2 | Secondary end point(s) |
Number of subjects with respiratory tract infection (RTI), lower respiratory tract infection (LRTI), severe LRTI and very severe LRTI associated with RSV infection;
Number of subjects with SAEs;
Number of subjects with RSV LRTI AE of special interest;
Titers of neutralizing antibodies against RSV type A;
Concentrations of RSV type F antibodies;
Palivizumab-competing antibody concentrations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year);
From first vaccination (Day 1) up to the end of the second RSV transmission season (up to 2 years);
From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year), and up to the end of the second RSV transmission season (up to 2 years);
At pre-vaccination (Screening), post-Dose 1 (Day 31) and post-Dose 2 (Day 61) and at the end of the first RSV transmission season (up to 1 year);
At pre-vaccination (Screening), post Dose 1 (Day 31) and post Dose 2 (Day 61) and at the end of the first RSV transmission season (up to 1 year);
At pre-vaccination (Screening), post Dose 1 (Day 31) and post-Dose 2 (Day 61)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
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 | 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 |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First administration in age group (6-7 month old infants) |
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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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.2.4 | Number of treatment arms in the trial | 15 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Colombia |
Finland |
Hong Kong |
Italy |
Mexico |
Panama |
Poland |
South Africa |
Spain |
Thailand |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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Last testing results released of samples collected at Visit 8 (end of the second RSV transmission season) related to primary and secondary endpoints. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |