Clinical trial NCT02927873: A Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK Biologicals' RSV Investigational Vaccine Based on Viral Proteins Encoded by Chimpanzee-derived Adenovector (ChAd155-RSV) (GSK3389245A) in RSV-seropositive Infants
Official title: A Phase 1/2, Randomized, Observer-blind, Controlled, Multi-center, Dose-escalation Study to Evaluate Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Respiratory Syncytial Virus (RSV) Investigational Vaccine Based on the RSV Viral Proteins F, N and M2-1 Encoded by Chimpanzee-derived Adenovector (ChAd155-RSV) (GSK3389245A), When Administered Intramuscularly According to a 0, 1-month Schedule to RSV-seropositive Infants Aged 12 to 23 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: Safety
Respiratory syncytial virus (RSV)
Immunogenicity
Reactogenicity
Infants
Vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-10-07
Enrollment: 107
Sex: ALL
Minimum age (years): 12
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of the respiratory syncytial virus (RSV) candidate vaccine when first administered via intramuscular (IM) injection according to a 0, 1-month schedule to RSV-seropositive infants aged 12 to 23 months.

Detailed description: The RSV PED-002 study, designed to evaluate the safety, reactogenicity and immunogenicity of the RSV candidate vaccine when administered in 3 sequential doses to seropositive infants aged 12 to 23 months, will be conducted in an observer-blind manner in Epoch 1 and single-blinded in Epoch 2.

Eligibility criteria: Inclusion Criteria:

* Subjects' parent(s)/ Legally acceptable representative (LAR\[s\]) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
* A male or female between, and including, 12 and 23 months at the time of the first vaccination.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Seropositive for RSV as determined by IBL International kit.
* Born full-term (i.e. after a gestation period of 37 to less than 42 completed weeks) with a minimum birth weight of 2.5 kg. (Required for Spain)
* Subjects' parent(s)/LAR(s) need to have access to a consistent mean of telephone contact or computer.

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -29 to Day 0), or planned use during the study period.
* Any medical condition that in the judgment of the investigator would make IM injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean prednisone, or equivalent. Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs or planned administration at any time during the study period.
* Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine administration, with the exception of scheduled routine pediatric vaccines which may be administered ≥ 14 days before a dose or ≥ 7 days after a dose.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Serious chronic illness.
* Major congenital defects.
* History of any neurological disorders or seizures.
* History of or current autoimmune disease.
* History of recurrent wheezing.
* History of chronic cough.
* Previous hospitalization for respiratory illnesses.
* History of thrombocytopenia.
* History of anemia.
* Previous, current or planned administration of Synagis.
* Neurological complications following any prior vaccination.
* Born to a mother known or suspected to be HIV-positive.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* Previous vaccination with a recombinant simian or human adenoviral vaccine.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
* Hypersensitivity to latex.
* Current severe eczema.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route. The preferred route for recording temperature in this study will be axillary.
  * Clinically significant upper respiratory tract infection
  * Subjects with a minor illness without fever may, be enrolled at the discretion of the investigator.
* Any clinically significant Grade 1 or any ≥ Grade 2 hematological or biochemical laboratory abnormality detected at the last screening blood sampling.
* Any other conditions that the investigator judges may interfere with study procedures or findings.
* Any conditions that could constitute a risk for the subjects while participating to this study.
* Weight below the fifth percentile of the local weight-for-age curve.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Planned move to a location that will prohibit participating in the trial until study end.

Primary outcomes:
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs)
timeFrame: During a 7-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)
measure: Number of Subjects With Any Solicited General AEs
timeFrame: During a 7-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)
measure: Number of Subjects With Any Unsolicited AEs
timeFrame: During a 30-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)
measure: Number of Subjects With Any Serious Adverse Events (SAEs) From Day 1 up to Day 61
timeFrame: From Day 1 up to Day 61
measure: Number of Subjects With Episode of Spontaneous or Excessive Bleeding (AE of Specific Interest)
timeFrame: During a 30-day follow-up period after each vaccination (vaccine/placebo administered at Day 1 and Day 31)
measure: Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 2
timeFrame: At Day 2
measure: Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 8
timeFrame: At Day 8
measure: Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 31
timeFrame: At Day 31
measure: Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 32
timeFrame: At Day 32
measure: Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 38
timeFrame: At Day 38
measure: Number of Subjects With Hematological Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 61
timeFrame: At Day 61
measure: Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 31
timeFrame: At Day 31
measure: Number of Subjects With Biochemical Laboratory Results Change With Respect to Normal Laboratory Ranges and Versus Baseline, at Day 61
timeFrame: At Day 61
Secondary outcomes:
measure: Number of Subjects With Any SAEs From Day 1 up to Day 366
timeFrame: From Day 1 up to Day 366
measure: Number of Subjects With Lower Respiratory Tract Infection Associated With RSV Infection (RSV-LRTI) (AE of Specific Interest) From Dose 1 Administration (Day 1) up to Day 366
timeFrame: From Dose 1 administration (Day 1) up to Day 366
measure: Number of Subjects With Respiratory Tract Infection Associated With RSV Infection (RSV-RTI), RSV-LRTI, Severe RSV-LRTI (According to Standardized Case Definitions) From Dose 1 Administration (Day 1) up to Day 366
timeFrame: From Dose 1 administration (Day 1) up to Day 366
measure: Number of Subjects With Any SAEs From Day 1 up to Study Conclusion at Day 731
timeFrame: From Day 1 up to study conclusion at Day 731
measure: Number of Subjects With RSV-LRTI (AE of Specific Interest) From Dose 1 Administration (Day 1) up to Study Conclusion at Day 731
timeFrame: From Dose 1 administration (Day 1) up to study conclusion at Day 731
measure: Number of Subjects With RSV-RTI, RSV-LRTI, Severe RSV-LRTI (According to Standardized Case Definitions) From Dose 1 Administration (Day 1) up to Study Conclusion at Day 731
timeFrame: From Dose 1 administration (Day 1) up to study conclusion at Day 731
measure: Frequency of RSV-specific CD4+ T-cells Expressing at Least Two Markers Upon Stimulation With F, N and M2-1 Peptide Pools
timeFrame: At Pre-vaccination (Screening), Day 31, Day 61 and Day 366
measure: Anti-RSV-A Neutralizing Antibody Titers
timeFrame: At Pre-vaccination (Screening), Day 31, Day 61 and Day 366
measure: Anti-RSV-F Antibody Concentrations
timeFrame: At Pre-vaccination (Screening), Day 31, Day 61 and Day 366
measure: Palivizumab-competing Antibody Concentrations
timeFrame: At Pre-vaccination (Screening), Day 31 and Day 61
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: Topeka
country: United States
facility: GSK Investigational Site
state: Kansas
city: Frederick
country: United States
facility: GSK Investigational Site
state: Maryland
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Sioux Falls
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Mexico
country: Mexico
facility: GSK Investigational Site
city: David
country: Panama
facility: GSK Investigational Site
state: Chiriquí
city: Panama
country: Panama
facility: GSK Investigational Site
city: Debica
country: Poland
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Hsinchu
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: