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Respiratory Syncytial Virus (RSV) Investigational Vaccine in Infants Aged 6 and 7 Months Likely to be Unexposed to RSV

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03636906
Recruitment Status : Active, not recruiting
First Posted : August 17, 2018
Last Update Posted : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE August 16, 2018
First Posted Date  ICMJE August 17, 2018
Last Update Posted Date July 29, 2020
Actual Study Start Date  ICMJE April 8, 2019
Actual Primary Completion Date January 16, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Number of subjects with any solicited local adverse events. [ Time Frame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days) ]
    Assessed solicited local adverse events are pain, redness and swelling. Any = occurrence of the adverse event regardless of intensity grade. Grade 3 pain = pain that prevents normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
  • Number of subjects with any solicited general adverse events [ Time Frame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days) ]
    Assessed solicited general adverse events are drowsiness, fever [defined as axillary temperature equal to or above 38.degrees Celsius (°C)], irritability/fussiness and loss of appetite. Any = occurrence of the adverse events regardless of intensity grade. Grade 3 irritability/fussiness/drowsiness = adverse event that prevented normal activity. Grade 3 fever = fever > 40.0 °C. Grade 3 loss of appetite = not eating at all. Related = adverse event assessed by the investigator as related to the vaccination.
  • Number of subjects with any unsolicited adverse events (AEs). [ Time Frame: During a 30-day follow-up period after each vaccination (i.e. the day of vaccination and 29 subsequent days). ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
  • Number of subjects with any serious adverse events (SAEs). [ Time Frame: From Day 1 up to Day 61 ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
  • Number of subjects with any AEs of specific interest. [ Time Frame: During a 30-day follow-up period after each vaccination (i.e. the day of vaccination and 29 subsequent days). ]
    AEs of specific interest include episodes of spontaneous or excessive bleeding.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Number of subjects with respiratory tract infection (RTI), lower respiratory tract infection (LRTI), severe LRTI and very severe LRTI associated with RSV infection [ Time Frame: From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year). ]
    RSV-RTI case definition includes runny nose, or blocked nose, or cough and confirmed RSV infection. RSV-LRTI case definition includes a history of cough or difficulty breathing and blood oxygen saturation (SpO2) lower than (<) 95 percent (%), or respiratory rate increased defined as respiratory rate higher than or equal to (≥) 50 per (/) minute (for 2-11 months of age) and ≥40/min (for 12 months of age or above) and confirmed RSV infection. RSV severe LRTI includes the RSV LRTI case definition and a SpO2 < 93%, or lower chest wall in-drawing. RSV very severe LRTI case definition meets the case definition of RSV-LRTI and a SpO2 <90%, or inability to feed, or failure to respond/unconscious.
  • Number of subjects with SAEs [ Time Frame: From first vaccination (Day 1) up to the end of the second RSV transmission season (up to 2 years). ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
  • Number of subjects with RSV LRTI AE of special interest [ Time Frame: From first vaccination (Day 1) up to the end of the first RSV transmission season (up to 1 year), and up to the end of the second RSV transmission season (up to 2 years). ]
    RSV-LRTI case definition includes a history of cough or difficulty breathing and blood oxygen saturation (SpO2) lower than (<) 95 percent (%), or respiratory rate increased defined as respiratory rate higher than or equal to (≥) 50 per (/) minute (for 2-11 months of age) and ≥40/min (for 12 months of age or above) and confirmed RSV infection.
  • Titers of neutralizing antibodies against RSV type A [ Time Frame: At pre-vaccination (Screening), post-Dose 1 (Day 31) and post-Dose 2 (Day 61) and at the end of the first RSV transmission season (up to 1 year). ]
    Titers are expressed as geometric mean titers (GMTs).
  • Concentrations of RSV type F antibodies [ Time Frame: At pre-vaccination (Screening), post-Dose 1 (Day 31) and post-Dose 2 (Day 61) and at the end of the first RSV transmission season (up to 1 year). ]
    RSV F antibody concentrations are expressed as geometric mean concentrations (GMCs).
  • Palivizumab-competing antibody concentrations. [ Time Frame: At pre-vaccination (Screening), post-Dose 1 (Day 31) and post-Dose 2 (Day 61) ]
    Concentrations of Palivizumab-competing antibodies are expressed as Geometric Mean Concentrations (GMCs).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Respiratory Syncytial Virus (RSV) Investigational Vaccine in Infants Aged 6 and 7 Months Likely to be Unexposed to RSV
Official Title  ICMJE 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 Infants
Brief Summary The purpose of this study is to provide critical information on the safety, reactogenicity and immunogenicity profile of the investigational recombinant chimpanzee adenovirus Type 155-vectored RSV (ChAd155-RSV) vaccine in infants likely to be unexposed to RSV, and will assess a single lower dose and a higher two dose regimen, before moving to future studies. This study will also assess if there is a risk of 'vaccine-induced enhanced RSV disease' after vaccination of these infants with the ChAd155-RSV vaccine.
Detailed Description The RSV PED-011 study is indicated as a Phase 1 in the study design due to programming limitations. In fact, the study is considered a Phase 1/2 and is designed to evaluate the safety, reactogenicity and immunogenicity of the RSV candidate vaccine when administered to infants aged 6 and 7 months before moving to a proof-of-concept trial in infants. The ChAd155-RSV vaccine will be administered before the RSV season to increase the probability of enrolling infants unexposed to RSV, who will be followed through two RSV seasons. For the 2 dose groups, the second dose of ChAd155-RSV vaccine will be given one month after the first dose. Approximately two thirds of the infants (100) in this study will be given the ChAd155-RSV vaccine, whereas all infants (150) will receive either an active control comparator vaccine (Bexsero, or Nimenrix, or Synflorix, or Menveo), or Placebo (Formulation buffer S9b). After a screening visit lasting up to 30 days (Epoch 1), this study will be conducted in an observer-blind manner, during the 2 month vaccination phase (Epoch 2) and in a single-blinded manner during the follow-up phase, for 10 months until the end of the first RSV season (Epoch 3) and then for an additional follow-up year, until the end of the second RSV season (Epoch 4).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Observer blind
Primary Purpose: Prevention
Condition  ICMJE Respiratory Syncytial Virus Infections
Intervention  ICMJE
  • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    2 doses of study vaccine administered intramuscularly in the left anterolateral thigh side, at Day 1 and Day 31
  • Biological: Bexsero
    3 doses of active comparator administered intramuscularly in the left anterolateral thigh side, at Day 61, Day 121 and at the end of RSV season, or at Day 1, Day 61 and end of RSV season.
  • Biological: Nimenrix
    3 doses of active comparator administered intramuscularly in the left anterolateral thigh side, at Day 61, Day 121 and at the end of RSV season, or at Day 1, Day 61 and end of RSV season.
  • Biological: Menveo
    2 doses of active comparator administered intramuscularly in the left anterolateral thigh side, at Day 61 and at the end of RSV season, or at Day 31 and end of RSV season.
  • Biological: Synflorix
    3 doses of active comparator administered intramuscularly in the left anterolateral thigh side, at Day 61, Day 121 and at the end of RSV season, or at Day 1, Day 61 and end of RSV season.
  • Drug: Placebo
    2 doses of placebo administered intramuscularly in the left anterolateral thigh side at Day 1 and Day 61, or at Day 31 and Day 121
Study Arms  ICMJE
  • Experimental: 1 Dose GSK3389245A + Bexsero Group
    Subjects, males or females between and including 6 and 7 months of age will receive 1 dose of the experimental GSK3389245A vaccine followed by placebo and Bexsero vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Bexsero
    • Drug: Placebo
  • Experimental: 2 Dose GSK3389245A + Bexsero Group
    Subjects, males or females between and including 6 and 7 months of age will receive 2 doses of the experimental GSK3389245A vaccine followed by Bexsero vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Bexsero
  • Active Comparator: Bexsero Group
    Subjects, males or females between and including 6 and 7 months of age will receive the Bexsero vaccine comparator and placebo
    Interventions:
    • Biological: Bexsero
    • Drug: Placebo
  • Experimental: 1 Dose GSK3389245A + Nimenrix Group
    Subjects, males or females between and including 6 and 7 months of age will receive 1 dose of the experimental GSK3389245A vaccine followed by placebo and Nimenrix vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Nimenrix
    • Drug: Placebo
  • Experimental: 2 Dose GSK3389245A + Nimenrix Group
    Subjects, males or females between and including 6 and 7 months of age will receive 2 doses of the experimental GSK3389245A vaccine followed by Nimenrix vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Nimenrix
  • Active Comparator: Nimenrix Group
    Subjects, males or females between and including 6 and 7 months of age will receive the Nimenrix comparator vaccine and placebo.
    Interventions:
    • Biological: Nimenrix
    • Drug: Placebo
  • Experimental: 1 Dose GSK3389245A + Menveo Group
    Subjects, males or females between and including 6 and 7 months of age will receive 1 dose of the experimental GSK3389245A vaccine followed by placebo and Menveo vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Menveo
    • Drug: Placebo
  • Experimental: 2 Dose GSK3389245A + Menveo Group
    Subjects, males or females between and including 6 and 7 months of age will receive 2 doses of the experimental GSK3389245A vaccine followed by Menveo vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Menveo
  • Active Comparator: Menveo Group
    Subjects, males or females between and including 6 and 7 months of age will receive the Menveo comparator vaccine and placebo.
    Interventions:
    • Biological: Menveo
    • Drug: Placebo
  • Experimental: 1 dose GSK3389245A + Synflorix Group
    Subjects, males or females between and including 6 and 7 months of age will receive1 dose of the experimental GSK3389245A vaccine followed by placebo and Synflorix vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Synflorix
    • Drug: Placebo
  • Experimental: 2 dose GSK3389245A + Synflorix Group
    Subjects, males or females between and including 6 and 7 months of age will receive2 doses of the experimental GSK3389245A vaccine followed by Synflorix vaccine
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Biological: Synflorix
  • Active Comparator: Synflorix Group
    Subjects, males or females between and including 6 and 7 months of age will receive the Synflorix comparator vaccine and placebo
    Interventions:
    • Biological: Synflorix
    • Drug: Placebo
  • Experimental: 1 dose GSK3389245A + Placebo
    Subjects, males or females between and including 6 and 7 months of age will receive the 1 dose of the GSK3389245A experimental vaccine followed by placebo.
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Drug: Placebo
  • Experimental: 2 dose GSK3389245A + Placebo
    Subjects, males or females between and including 6 and 7 months of age will receive the 2 doses of the GSK3389245A experimental vaccine followed by placebo.
    Interventions:
    • Biological: Respiratory syncytial virus (RSV) vaccine GSK3389245A
    • Drug: Placebo
  • Placebo Comparator: Placebo Group
    Subjects, males or females between and including 6 and 7 months of age will receive the Placebo vaccine
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 12, 2019)
201
Original Estimated Enrollment  ICMJE
 (submitted: August 16, 2018)
150
Estimated Study Completion Date  ICMJE August 31, 2021
Actual Primary Completion Date January 16, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 performing any study specific procedure.
  • A male or female between and including 6 and 7 months of age (from the day the infant becomes 6 months of age until the day before the infant achieves 8 months of age) at the time of the first vaccination.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Born full-term with a minimum birth weight of 2.5 kilograms (kg).
  • 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 1), or planned use during the study period.
  • 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 ≥ 0.5 milligrams (mg)/kg/day (for pediatric subjects), or equivalent. 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. Scheduled routine pediatric vaccines may be administered ≥ 7 days before a dose of study vaccine or ≥ 7 days following a dose of study vaccine, with the exception of live viral 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.
  • A history of, or on-going confirmed RSV disease or highly compatible clinical picture.
  • Serious chronic illness.
  • Major congenital defects.
  • History of any neurological disorders or seizures.
  • History of or current autoimmune disease.
  • History of recurrent wheezing in the subject's lifetime.
  • History of chronic cough.
  • Previous hospitalization for lower respiratory illnesses.
  • Previous, current or planned administration of Synagis (palivizumab).
  • Neurological complications following any prior vaccination.
  • Born to a mother known or suspected to be Human Immunodeficiency Virus (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 to any component of the vaccines (investigational or control) or placebo used in this study or any contraindication to them.
  • Hypersensitivity to latex.
  • Current severe eczema.
  • Acute disease and/or fever at the time of enrolment (Visit 1).
  • Any clinically significant Grade 1 or any ≥ Grade 2 hematological or biochemical laboratory abnormality detected at the last screening blood sampling.
  • Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe.
  • Any other conditions that the investigator judges may interfere with study procedures, 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 according to the World Health Organization (WHO) weight- for- age tables. Participating in another clinical study, at any time during the study period, in which the subject or mother (if breastfeeding) 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.
  • For Thailand only, subjects who have received Synflorix prior to enrolment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 7 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   Colombia,   Finland,   Italy,   Mexico,   Panama,   Poland,   Spain,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries Argentina,   Australia,   Belgium,   Hong Kong,   Russian Federation
 
Administrative Information
NCT Number  ICMJE NCT03636906
Other Study ID Numbers  ICMJE 204894
2018-000431-27 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP