E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylactic respiratory syncytial virus (RSV) vaccine. |
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E.1.1.1 | Medical condition in easily understood language |
Preventive vaccine against RSV. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 |
1. To assess the safety and tolerability of an intramuscular regimen of two doses of 1x10e11 viral particles (vp) of Ad26.RSV.preF in adults aged 18 to 50 years. 2. To assess the safety and tolerability of an intramuscular regimen of two doses of 5x10e10 vp of Ad26.RSV.preF in RSV-seropositive toddlers aged 12 to 24 months.
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E.2.2 | Secondary objectives of the trial |
To assess the humoral and cellular immune responses as measured by virus neutralization assay, F-protein binding antibodies (pre-F and post-F) and intracellular cytokine staining (ICS; to assess T-helper (Th1/Th2) subtyping).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult subjects: - Signed informed consent form (ICF) - Aged between ≥18 and ≤50 years old - In good health, without significant medical illness, on the basis of physical examination, medical history, and vital signs measurement - Healthy on the basis of clinical laboratory tests performed at screening -Contraceptive use by men or women consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies. - Women of childbearing potential must practise an effective method of contraception. - Women of childbearing potential must have a negative pregnancy test at screening and immediately prior to each study vaccine administration - Subject must agree not to donate blood from first vaccination until 3 months after the final dose.
Paediatric subjects: - Informed consent form (ICF) signed by parent/ legal guardian - Aged between ≥12 months to ≤24 months - Born out of normal term pregnancy ≥37 weeks, with a minimum birth weight of 2.5 kg - In good health without any significant medical illness on the basis of physical examination, medical history, and vital signs performed at screening - Received all routine immunizations appropriate for his or her age according to local guidelines - Parent/ local guardian must have access to a consistent means of contact either by telephone contact or email/computer
Full details are available in section 4 of the protocol. |
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E.4 | Principal exclusion criteria |
Adult subjects: - Acute illness or temperature ≥38.0 ºC/100.4 °F within 24 hours prior to the first dose of study vaccine - History of an underlying clinically significant acute or chronic medical condition or other unsuitable physical examination findings - History of malignancy within 5 years before screening (exceptions defined in the protocol) - Major surgery within 12 weeks before dosing, or will not have fully recovered from surgery, or has surgery planned during participation in the study or within 6 months after the last dose of study vaccine -Chronic active hepatitis B or hepatitis C infection - HIV-1 or HIV-2 infection - Psychiatric illness and/or drug or alcohol abuse - Received or planning to receive other vaccines during the study (vaccine types and time window defined in the protocol) - Participation in other interventional trial/ receipt of other investigational drug or medical device (as defined in the protocol) - Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components - History of chronic urticaria, eczema or atopic dematitis - History of acute polyneuropathy - Abnormal function of the immune system - Contraindication to intramuscular injections and blood draws - Pregnancy (incl. planned pregnancy) or breast-feeding - Employee of the investigator or the study site directly involved in the study and family members of either the investigator, study-site employee, or employee of the sponsor - Subject who cannot communicate reliably with the investigator - Subject at risk of not adhering to the requirements of the study or dosing schedule
Paediatric subjects: - Moderate or severe illness or temperature ≥38.0 ºC/100.4 °F within 24 hours prior to the first dose of study vaccine - Weight is below 10th percentile according to World Health Organization (WHO) pediatric growth and weight charts - Clinically significant acute or chronic medical condition that, in the opinion of the investigator, would preclude participation (as detailed in the protocol) - Major congenital anomalies or known cytogenetic disorders - Major surgery within the 4 weeks prior to randomization or has planned major surgery through the course of the study - Received or planning to receive other vaccines during the study (vaccine types and time window defined in the protocol) - Known or suspected immunodeficiency, such as known HIV infection - Participation in other interventional trial/ receipt of other investigational drug or medical device (as defined in the protocol) - - Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components - History of chronic urticaria, eczema or atopic dematitis - History of acute polyneuropathy - Chronic or recurrent use of immunomodulators/suppressors, oral or parenteral corticosteroids for at least 5 days within 42 days prior to randomization, or planned during the course of the study - History of receipt of blood products or immunoglobulin within 3 months of randomization or receipt of palivizumab/Synagis® at any time prior to randomization - Contraindication to intramuscular injections and blood draws - Parent/ legal guardian cannot communicate reliably with the investigator - Family member of either the investigator, study-site employee, or employee of the sponsor.
Full details are available in section 4 of the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Solicited local and systemic adverse events (AEs) for 7 days after each vaccination. 2. Unsolicited AEs for 28 days after each vaccination (ie, from informed consent form [ICF] signature through the following 28 days post-first vaccination, and for subsequent vaccinations from time of vaccination through the following 28 days). 3. SAEs from ICF signature until the end of the study.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. For 7 days after each vaccination 2. For 28 days after each vaccination 3. From ICF signature until the end of the study |
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E.5.2 | Secondary end point(s) |
Immune Responses: The analysis of the immunogenicity of vaccine regimens will include the characterization of humoral as well as cellular responses. The focus of the immunogenicity analysis is on virus neutralizing antibodies (VNAs), F-protein antibodies (pre-F and/or post-F) and Th1/Th2 cytokine profile response. A) Humoral Immune Response - RSV neutralization A strain; Analysis of RSV A neutralizing antibodies. - RSV F-protein enzyme-linked immunosorbent assay (ELISA; pre- and/or post-fusion F antibodies); Analysis of antibodies binding to RSV F protein in post-fusion and pre-fusion form. B) Cell-mediated Immune Response - Intracellular cytokine staining or cytokine analysis; Analysis of CD4 and CD8 T-cell subsets and their cytokine expression patterns will be determined by flow cytometry after RSV F-protein peptide stimulation (including, but not limited to CD4/CD8, interleukin-2 [IL-2], IFNγ, tumor necrosis factor alpha (TNFα) and Th1/Th2 subtyping).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pre-vaccination for 1st and 2nd doses and at 28 days post Dose 2 and 6 months post Dose 2. |
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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 | 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 | 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 |
Tolerability, Immunogenicity |
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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 |
Safety, Tolerability and Immunogenicity |
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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 | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 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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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 |