A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.RSV.preF in respiratory syncytial virus (RSV)-seronegative Toddlers

Phase 1

Conditions: Prophylactic respiratory syncytial virus (RSV)
MedDRA version: 21.1Level: PTClassification code 10061603Term: Respiratory syncytial virus infectionSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2017-003859-36-FI

Lead Sponsor: Janssen Vaccines and Prevention B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 36

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 36
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 ß2 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 corticostero

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: The secondary objectives are:<br>• 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.<br>• To monitor for severe RSV-lower respiratory tract infection (LRTI) as a preliminary indication of enhanced respiratory disease (ERD).;Main Objective: 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.;Primary end point(s): 1. Solicited local and systemic adverse events (AEs)<br>2. Unsolicited AEs<br>3. Serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: 1. For 7 days after each vaccination<br>2. For 28 days after each vaccination<br>3. From first dose administration to the end of the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Humoral Immune Response - RSV neutralization A strain<br>2. Humoral Immune Response - F protein antibodies (enzyme-linked immunosorbent assay [ELISA]; pre- and/or post-F)<br>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<br>4. RSV Infection - Severe RSV-LRTI;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 <br>3. Either at screening or prior to vaccination on Day 1, Day 85 and/or early exit<br>4. From first dose to the end of the study