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

Respiratory Syncytial Virus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03606512
• Other study ID #: CR108465
• Secondary ID: 2017-003859-36VA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 21, 2019
• Est. completion date: November 2, 2021

Study information

• Verified date: November 2023
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: November 2, 2021
• Est. primary completion date: November 2, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 24 Months

Eligibility

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

Related Conditions & MeSH terms

• Respiratory Syncytial Virus

Intervention

Biological:
• Ad26.RSV.preF
Ad26.RSV.preF will be administered as IM injection at a dose of 2.5*10^10 vp.
• Placebo
Placebo will be administered as IM injection of sterile 0.9 percent (%) saline for injection.
• Nimenrix
Nimenrix will be administered as 0.5 milliliter (mL) solution for IM injection.

Locations

Country	Name	City	State
Australia	Barwon Health	Geelong
Australia	Telethon Kids Institute	Nedlands
Australia	Murdoch Children's Research Institute	Parkville
Brazil	Complexo Hospital de Clinicas - UFPR	Curitiba
Brazil	Hospital Pequeno Principe	Curitiba
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS	Porto Alegre
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	McGill University Health Centre - Vaccine Study Centre	Pierrefonds	Quebec
Canada	CHU de Québec Université Laval	Quebec
Finland	Järvenpään rokotetutkimusklinikka	Järvenpää
Finland	Tampereen rokotetutkimusklinikka	Tampere
Finland	Turun rokotetutkimusklinikka	Turku
Poland	Jerzy Brzostek Prywatny Gabinet Lekarski	Debica
Poland	Szpital im. Swietej Jadwigi Slaskiej, Oddzial Pediatryczny z Pododdzialem Niemowlecym	Trzebnica
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Clinico Univ. de Santiago	Santiago de Compostela
Sweden	Sachsska barn-och ungdomssjukhuset	Stockholm
Sweden	Norrlands Universitetssjukhus	Umeå
United Kingdom	Imperial College London	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Countries where clinical trial is conducted

Australia,  Brazil,  Canada,  Finland,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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