E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylactic respiratory syncytial virus (RSV) |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061603 |
E.1.2 | Term | Respiratory syncytial virus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
The primary objective is to assess the safety and reactogenicity of an intramuscular regimen of 3 doses of 2.5×10e10 viral particles (vp) of Ad26.RSV.preF in RSV-seronegative toddlers aged 12 to 24 months. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • To assess the humoral and cellular immune responses elicited by Ad26.RSV.preF as measured by virus neutralizing antibodies (VNAs), F protein binding antibodies (pre-F and/or post-F), and T-helper (Th)1/Th2 subtyping. • To monitor for severe RSV-lower respiratory tract infection (LRTI) as a preliminary indication of enhanced respiratory disease (ERD). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each potential subject must satisfy all of the following criteria to be enrolled in the study: 1. Each subject’s parent(s)/legal guardian(s) must sign an informed consent form (ICF) indicating that he/she understands the purpose of and procedures required for the study, are willing for his/her child to participate in the study and attend all scheduled visits, and are willing and able to comply with all study procedures, including maintaining contact with the site for 2 RSV seasons following the first dose, and adhere to the prohibitions and restrictions specified in this protocol. Note: For each subject, at least one parent or legal guardian, according to local regulations, must give written consent. In countries where regulation requires that both parents/legal guardians give consent, this will be applicable. 2. Subject is male or female, whose age on the day of ICF signature is ≥12 months to ≤24 months and who is seronegative for RSV within 42 days prior to dosing. Note: Serostatus may be assessed via the RSV enzyme immunoassay (EIA) if available from a different study of the sponsor (VAC18194RSV2001). If done within 42 days of first dose, this assessment would not have to be repeated in the absence of a history of respiratory infection during that period. 3. Subject is the product of a normal term pregnancy ≥37 weeks, with a minimum birth weight of 2.5 kilogram (kg). 4. Subject must be in good health without any significant medical illness on the basis of physical examination, medical history, and vital signs performed at screening. 5. Subject has received all routine immunizations appropriate for his or her age according to local guidelines. 6. Each subject’s parent(s)/legal guardian(s) must have access to a consistent means of contact either by telephone contact or email/computer. |
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E.4 | Principal exclusion criteria |
Any potential subject who meets any of the following criteria will be excluded from participating in the study: 1. Subject has moderate or severe illness (this does not include minor illnesses such as diarrhea) or temperature ≥38.0 ºC within 24 hours prior to the first dose of study vaccine; the subject may be enrolled at a later date, or be withdrawn at the discretion of the investigator and after consultation with the sponsor. 2. Any subject who has had an respiratory tract infection (RTI) between screening and randomization that the principal investigator(s) [PI(s)] feels would make them ineligible. 3. Subject’s weight is below 10th percentile according to World Health Organization (WHO) pediatric growth and weight charts. 4. Subject has any clinically significant acute or chronic medical condition (eg, history of seizure disorders, bleeding/clotting disorder, autoimmune disease, active malignancy, systemic infections, congenital heart disease, history of any pulmonary condition requiring medication, atopy, reactive airway disease, medically-confirmed wheezing, bronchoconstriction or treatment with a β2 agonist, cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically-confirmed apnea, hospitalization for respiratory illness, or mechanical ventilation for respiratory illness) that, in the opinion of the investigator, would preclude participation. 5. Subject has major congenital anomalies (after discussion with the study responsible physician/ scientist [SRP/S]) or known cytogenetic disorders (eg, Down’s syndrome). 6. Subject has had major surgery within the 4 weeks prior to randomization or has planned major surgery through the course of the study. 7. Subject is in receipt of, or planning to receive, live attenuated vaccine (eg, measles, mumps and rubella [MMR] or varicella, but excluding rotavirus vaccine) within 28 days of each study vaccination (ie, before and after); other vaccines (eg, influenza, pertussis, polio or rotavirus) should be given at least 14 days before or 14 days after each study vaccination. Note: Planning for routine childhood vaccinations will be available from the site to ensure that these can be taken at appropriate times during the study. 8. Subject has known or suspected immunodeficiency, such as known human immunodeficiency virus (HIV) infection. 9. Subject has received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of the first dose of study vaccine or is currently enrolled or plans to participate in another investigational study during this study. Note: Participation in an observational clinical study (ie, with no intervention) is allowed upon approval of the sponsor. 10. Subject has a known allergy to vaccines or vaccine components (including any of the constituents of the study vaccine), or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine). Note: subjects with egg allergies can be enrolled. 11. Subject has a history of the following moderate to severe chronic conditions: urticaria (recurrent hives), eczema and/or atopic dermatitis. 12. Subject has a history of acute polyneuropathy (eg, Guillain-Barré syndrome). 13. Subject has chronic or recurrent use of immunomodulators/suppressors, eg, cancer chemotherapeutic agents, oral or parenteral corticosteroids for at least 5 days within 42 days prior to randomization, or planned during the study. 14. Subject has a history of receipt of blood products or immunoglobulin within 3 months of randomization. 15. Subject has been in receipt of palivizumab/Synagis® or received any other vaccine or monoclonal/polyclonal antibody in a previous RSV study at any time prior to randomization. 16. Subject has a contraindication to intramuscular injections and blood draws, eg, bleeding disorders. 17. Subject has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. 18. Subject’s parent(s)/legal guardian(s) cannot communicate reliably with the investigator. 19. Subject is a family member of either the investigator, an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, or employee of the sponsor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Solicited local and systemic adverse events (AEs) 2. Unsolicited AEs 3. Serious adverse events (SAEs) |
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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 first dose administration to the end of the study |
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E.5.2 | Secondary end point(s) |
1. Humoral Immune Response - RSV neutralization A strain 2. Humoral Immune Response - F protein antibodies (enzyme-linked immunosorbent assay [ELISA]; pre- and/or post-F) 3. Cell-mediated Immune Response - Flow cytometry (intracellular cytokine staining [ICS]) - Analysis of T-cell responses to RSV F protein peptides for Th1/Th2 subtyping 4. RSV Infection - Severe RSV-LRTI |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 and 2. Either at screening or prior to vaccination on Day 1, Day 8, Day 85, end of first RSV season and/or early exit 3. Either at screening or prior to vaccination on Day 1, Day 85 and/or early exit 4. From first dose to the end of the study |
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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 |
Reactogenicity and 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, Reactogenicity, and Immunogenicity study |
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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) | Yes |
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 | 15 |
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 |
Australia |
Brazil |
Canada |
Finland |
Poland |
Spain |
Sweden |
United Kingdom |
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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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The end of the study will be the last subject’s last visit (by telephone) at the end of the safety follow-up phase through 2 RSV seasons after the first dose. |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 27 |