A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Adenovirus Serotype 26 Based Respiratory Syncytial Virus Pre-fusion (Ad26.RSV.Pre-F) Vaccine in RSV-Seronegative Toddlers 12 to 24 Months of Age

A Randomized, Controlled, Observer-blind, Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers 12 to 24 Months of Age

The purpose of this study is to assess the safety and reactogenicity of an intramuscular regimen of 3 doses of 2.5*10^10 viral particles (vp) of adenovirus serotype 26 based respiratory syncytial virus pre-fusion protein (Ad26.RSV.preF) vaccine in RSV-seronegative toddlers aged 12 to 24 months.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Biological: Ad26.RSV.preF; Biological: Placebo; Biological: Nimenrix

Detailed Description

RSV is considered the most important cause of serious acute respiratory illness in children under 5 years of age. Ad26.RSV.preF (JNJ-64400141) investigational vaccine is a replication-incompetent serotype 26 adenoviral vector (Ad26) containing a deoxyribonucleic acid (DNA) transgene that encodes for the F protein derived from the respiratory syncytial virus (RSV) A2 strain stabilized in the pre-fusion conformation (Ad26.RSV.preF). The study will evaluate whether Ad26.RSV.preF is safe, well-tolerated, and immunogenic in RSV-seronegative toddlers. The study will have 3 phases: a screening phase (up to 6 weeks before the first dose), a vaccination phase (34 weeks), and a safety follow-up phase through 2 RSV seasons after the first dose. RSV infection will be monitored by active and passive surveillance. The total duration of the study will be approximately 26 months.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Geelong, Australia, 3220
    • Barwon Health
  • Nedlands, Australia, 6009
    • Telethon Kids Institute
  • Parkville, Australia, 3052
    • Murdoch Children's Research Institute
• Brazil
  • Curitiba, Brazil, 80030-110
    • Complexo Hospital de Clinicas - UFPR
  • Curitiba, Brazil, 80250-060
    • Hospital Pequeno Principe
  • Porto Alegre, Brazil, 90035-074
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS
• Canada
  • Quebec, Canada, G1V 4G2
    • Chu de Quebec Universite Laval
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • Dalhousie University
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Pierrefonds, Quebec, Canada, H9H 4Y6
      • McGill University Health Centre - Vaccine Study Centre
• Finland
  • Järvenpää, Finland, 04400
    • Järvenpään Rokotetutkimusklinikka
  • Tampere, Finland, 33100
    • Tampereen Rokotetutkimusklinikka
  • Turku, Finland, 20520
    • Turun Rokotetutkimusklinikka
• Poland
  • Debica, Poland, 39-200
    • Jerzy Brzostek Prywatny Gabinet Lekarski
  • Trzebnica, Poland, 55-100
    • Szpital im. Swietej Jadwigi Slaskiej, Oddział Pediatryczny z Pododdziałem Niemowlęcym
• Spain
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Santiago de Compostela, Spain, 15706
    • Hosp. Clinico Univ. de Santiago
• Sweden
  • Stockholm, Sweden, 11861
    • Sachsska barn-och ungdomssjukhuset
  • Umeå, Sweden, 90185
    • Norrlands Universitetssjukhus
• United Kingdom
  • London, United Kingdom, W21PG
    • Imperial College London
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
  • Southampton, United Kingdom, SO166YD
    • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant who is seronegative for respiratory syncytial virus (RSV) within 42 days prior to dosing
• Participant is the product of a normal term pregnancy greater than or equal to (>=)37 weeks, with a minimum birth weight of 2.5 kilogram (kg)
• Participant must be in good health without any significant medical illness on the basis of physical examination, medical history, and vital signs performed at screening
• Participant has received all routine immunizations appropriate for his or her age according to local guidelines
• Each participant's parent(s)/legal guardian(s) must have access to a consistent means of contact either by telephone contact or email/computer

Exclusion Criteria:

• Participant's weight is below tenth percentile according to World Health Organization (WHO) pediatric growth and weight charts
• Participant has any clinically significant acute or chronic medical condition (for example, 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 beta 2 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
• Participant is in receipt of, or planning to receive, live attenuated vaccine (for example, measles, mumps and rubella [MMR] or varicella, but excluding rotavirus vaccine) within 28 days of each study vaccination (that is, before and after); other vaccines (for example, influenza, pertussis, polio or rotavirus) should be given at least 14 days before or 14 days after each study vaccination
• Participant has known or suspected immunodeficiency, such as known human immunodeficiency virus (HIV) infection
• Participant 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). Participants with egg allergies can be enrolled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: RSV Seronegative Toddlers (Ad26.RSV.preF); Respiratory syncytial virus (RSV) seronegative toddlers will receive intramuscular (IM) injection of 2.5*10^10 viral particles (vp) of an adenovirus serotype 26- based vaccine encoding for the respiratory syncytial virus pre-fusion F-protein on Days 1, 29, and 57.	Biological: Ad26.RSV.preF; Ad26.RSV.preF will be administered as IM injection at a dose of 2.5*10^10 vp.; Other Names: JNJ-64400141
Placebo Comparator: Group 2: RSV Seronegative Toddlers (Placebo/Nimenrix); RSV seronegative toddlers will receive IM injection of placebo on Days 1, 29 and 57. Placebo can be replaced with Nimenrix on Day 57 in countries where applicable.	Biological: Placebo; Placebo will be administered as IM injection of sterile 0.9 percent (%) saline for injection.; Biological: Nimenrix; Nimenrix will be administered as 0.5 milliliter (mL) solution for IM injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 7 Days After First Vaccination	An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Solicited local and systemic AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included injection-site pain/tenderness, injection-site erythema and injection-site swelling/induration. Solicited systemic AEs included fatigue, headache, nausea, myalgia and fever.	Up to Day 8 (7 days after first vaccination on Day 1)
Number of Participants With Solicited Local and Systemic AEs for 7 Days After Second Vaccination	An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Solicited local and systemic AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included injection-site pain/tenderness, injection-site erythema and injection-site swelling/induration. Solicited systemic AEs included fatigue, headache, nausea, myalgia and fever.	Up to Day 36 (7 days after second vaccination on Day 29)
Number of Participants With Solicited Local and Systemic AEs for 7 Days After Third Vaccination	An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Solicited local and systemic AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included injection-site pain/tenderness, injection-site erythema and injection-site swelling/induration. Solicited systemic AEs included fatigue, headache, nausea, myalgia and fever.	Up to Day 64 (7 days after third vaccination on Day 57)
Number of Participants With Unsolicited AEs for 28 Days After First Vaccination	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Unsolicited AEs were precisely defined events that participants were not asked about and which were not noted by participants in the diary.	Up to Day 29 (28 days after first vaccination on Day 1)
Number of Participants With Unsolicited AEs for 28 Days After Second Vaccination	An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Unsolicited AEs were precisely defined events that participants were not asked about and which were not noted by participants in the diary.	Up to Day 57 (28 days after second vaccination on Day 29)
Number of Participants With Unsolicited AEs for 28 Days After Third Vaccination	An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Unsolicited AEs were precisely defined events that participants were not asked about and which were not noted by participants in the diary.	Up to Day 85 (28 days after third vaccination on Day 57)
Number of Participants With Serious Adverse Events (SAEs)	Number of participants with SAEs were reported. An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a suspected transmission of any infectious agent via a medicinal product, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to 2 year 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers of Neutralizing Antibodies to Respiratory Syncytial Virus (RSV) A2 Strain	Neutralizing antibody titers assessed by virus neutralizing antibodies (VNA) against the RSV A2 strain were expressed as 50% inhibitory concentration (IC50) units.	Days 1, 8, 85, and 267 (End of first RSV season)
Pre-Fusion A Immunoglobulin G (IgG) Serum Antibody Response as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)	Pre-fusion A IgG serum antibody response was assessed by ELISA.	Days 1, 8, 85, and 267 (End of first RSV season)
Post-Fusion A IgG Serum Antibody Response as Assessed by ELISA	Post-fusion A IgG serum antibody response as assessed by ELISA was reported.	Days 1, 8, 85, and 267 (End of first RSV season)
T-cell Response (Percent [%]) to RSV F Peptides for T-helper (Th) 1 and Th2 Subtyping as Measured by Flow Cytometry	T-cell response (%) to RSV F peptides for T-helper Th1 and Th2 subtyping as measured by flow cytometry was planned to be assessed. Th1(% of Clusters of differentiation 4 [CD4]+ interferon gamma [IFN-g]+T cells; lower limit(s) of quantification [LLOQ]=0.05%) and Th2 (% of CD4+ interleukin [IL]-4+/IL-13+ and CD40L+T cells; LLOQ=0.07%) responses were determined by intracellular cytokines after RSV F peptide stimulation.	Baseline (Day 1) and Day 85
Number of Participants With Severe RSV-lower Respiratory Tract Infection (LRTI)	Number of participants with severe RSV-LRTI were reported.	Up to 2 year 10 months

Collaborators and Investigators

• Sponsor: Janssen Vaccines & Prevention B.V.
• Investigators: Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial, Janssen Vaccines & Prevention B.V.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Actual): November 2, 2021
• Study Completion (Actual): November 2, 2021

Study Registration Dates

• First Submitted: June 20, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: CR108465; 2017-003859-36 (EudraCT Number); VAC18194RSV2002 (Other Identifier: Janssen Vaccines & Prevention B.V.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes