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Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine, LID/ΔM2-2/1030s, in RSV-Seronegative Infants and Children 6 to 24 Months of Age

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ClinicalTrials.gov Identifier: NCT04520659
Recruitment Status : Not yet recruiting
First Posted : August 20, 2020
Last Update Posted : August 20, 2020
Sponsor:
Collaborator:
Sanofi Pasteur, a Sanofi Company
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE August 13, 2020
First Posted Date  ICMJE August 20, 2020
Last Update Posted Date August 20, 2020
Estimated Study Start Date  ICMJE September 1, 2020
Estimated Primary Completion Date December 23, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Frequency of Grade 1 or higher solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]
    May include fever, acute otitis media, rhinorrhea, pharyngitis, cough without lower respiratory infection (LRI), or hoarseness
  • Frequency of Grade 2 or higher lower respiratory infections (LRI) [ Time Frame: Measured through Day 28 ]
    May include wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi, rales
  • Frequency of serious adverse events (SAEs) [ Time Frame: Measured through Day 56 ]
  • Percentage of vaccinees with a ≥4-fold rise in serum RSV-neutralizing antibody titer [ Time Frame: Measured at Day 56 ]
  • Peak titer of vaccine virus shed [ Time Frame: Measured through Day 28 ]
    Detected by immunoplaque assay and/or RT-qPCR. Group 1 participants only.
  • Proportion of vaccinees infected with vaccine virus in Group 1 [ Time Frame: Measured through Day 56 ]
    Defined as shedding vaccine virus, detected by immunoplaque assay and/or RT-qPCR, and/or ≥4-fold rise in RSV-specific serum antibodies, detected by enzyme-linked immunosorbent assay (ELISA) against the RSV F protein and/or an RSV-PRNT
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Frequency of RSV-medically attended acute respiratory illness (MAARI) [ Time Frame: Measured during RSV season (from October 16 through March 31) ]
  • Maximum grade of RSV MAARI [ Time Frame: Measured during RSV season (from October 16 through March 31 ]
  • Frequency of RSV-medically attended acute lower respiratory illness (MAALRI) [ Time Frame: Measured during RSV season (from October 16 through March 31) ]
  • Maximum grade of RSV MAALRI [ Time Frame: Measured during RSV season (from October 16 through March 31) ]
  • Percentage of vaccinees with a ≥4-fold rise in serum RSV F IgG [ Time Frame: Measured at Day 56 ]
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 Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine, LID/ΔM2-2/1030s, in RSV-Seronegative Infants and Children 6 to 24 Months of Age
Official Title  ICMJE Phase Ib Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine, LID/ΔM2-2/1030s, Lot RSV#010A, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
Brief Summary The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age.
Detailed Description

This study will evaluate the infectivity, safety, and immunogenicity of a single dose of a recombinant, live-attenuated respiratory syncytial virus (RSV) vaccine, LID/ΔM2-2/1030s, in RSV-seronegative infants and children 6 to 24 months of age.

Participants will be randomly assigned to one of two groups to receive a single dose of intranasal RSV LID/ΔM2-2/1030s vaccine or placebo at study entry (Day 0). Group 1 (intensive) and Group 2 (less intensive) will differ only in the frequency of study visits and nasal swab collections.

Participants will receive study product between April 1 and October 15, outside of the RSV season, and will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration is between 6 and 13 months, depending upon time of enrollment.

Participants will attend several study visits throughout the study, which may include blood collection, nasal swabs, and physical examinations.

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)
Primary Purpose: Prevention
Condition  ICMJE RSV Infection
Intervention  ICMJE
  • Biological: RSV LID/ΔM2-2/1030s
    10^5 plaque-forming units (PFU); administered as nose drops
  • Biological: Placebo
    Administered as nose drops
Study Arms  ICMJE
  • Experimental: Group 1: RSV LID/ΔM2-2/1030s
    Participants will receive a single dose of RSV LID/ΔM2-2/1030s vaccine at study entry (Day 0).
    Intervention: Biological: RSV LID/ΔM2-2/1030s
  • Placebo Comparator: Group 1: Placebo
    Participants will receive a single dose of placebo at study entry (Day 0).
    Intervention: Biological: Placebo
  • Experimental: Group 2: RSV LID/ΔM2-2/1030s
    Participants will receive a single dose of RSV LID/ΔM2-2/1030s vaccine at study entry (Day 0).
    Intervention: Biological: RSV LID/ΔM2-2/1030s
  • Placebo Comparator: Group 2: Placebo
    Participants will receive a single dose of placebo at study entry (Day 0).
    Intervention: Biological: 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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2020)
81
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2022
Estimated Primary Completion Date December 23, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ≥ 6 months of age and < 25 months of age at the time of inoculation
  • Screening and pre-inoculation serum specimens for respiratory syncytial virus (RSV)-neutralizing antibody are obtained no more than 42 days prior to inoculation
  • Seronegative for RSV antibody, defined as serum RSV-neutralizing antibody titer <1:40
  • In good health based on review of the medical record, history, and physical examination at the time of inoculation
  • Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
  • Growing normally for age as demonstrated on a World Health Organization (WHO) growth chart, AND

    • If < 1 year of age: has a current height and weight above the 5th percentile for age
    • If ≥ 1 year of age: has a current height and weight above the 3rd percentile for age
  • Expected to be available for the duration of the study
  • Parent/guardian is willing and able to provide written informed consent

Exclusion Criteria:

  • ≤ 6 months of age and > 25 months of age at the time of inoculation
  • Born at less than 34 weeks gestation
  • Born at less than 37 weeks gestation, and at the date of inoculation less than 1 year of age
  • Maternal history of a positive HIV test before or during pregnancy
  • Evidence of chronic disease
  • Known or suspected infection or impairment of immunological functions
  • Bone marrow/solid organ transplant recipient
  • Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
  • Suspected or documented developmental disorder, delay, or other developmental problem
  • Cardiac abnormality requiring treatment
  • Lung disease or reactive airway disease
  • More than one episode of medically diagnosed wheezing in the first year of life
  • Wheezing episode or received bronchodilator therapy within the past 12 months
  • Wheezing episode or received bronchodilator therapy after the age of 12 months
  • Previous receipt of supplemental oxygen therapy in a home setting
  • Previous receipt of an investigational RSV vaccine
  • Previous receipt or planned administration of anti-RSV antibody product including ribavirin, RSV Ig, or RSV mAb
  • Previous receipt of immunoglobulin or any antibody products within the past 6 months
  • Previous receipt of any blood products within the past 6 months
  • Previous anaphylactic reaction
  • Previous vaccine-associated adverse reaction that was Grade 3 or above
  • Known hypersensitivity to any study product component
  • Member of a household that contains an infant who is less than 6 months of age at the date of inoculation through the 28th day after inoculation
  • Member of a household that, at the date of inoculation through the 28th day after inoculation, contains an immunocompromised individual including but not limited to:

    • a person who is HIV-infected
    • a person who has cancer and has received chemotherapy within the 12 months prior to enrollment
    • a person living with a solid organ or bone marrow transplant
  • Attends a daycare facility that does not separate children by age and contains an infant <6 months of age at the date of inoculation through the 28th day after inoculation
  • Receipt of any of the following prior to enrollment:

    • inactivated influenza vaccine within 3 days prior, or
    • any other inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
    • any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
    • another investigational vaccine or investigational drug within 28 days prior, or
    • salicylate (aspirin) or salicylate-containing products within the past 28 days
  • Scheduled administration of any of the following after planned inoculation

    • inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
    • any live vaccine other than rotavirus in the 28 days after, or
    • another investigational vaccine or investigational drug in the 56 days after
  • Receipt of any of the following medications within 3 days of study enrollment:

    • systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
    • intranasal medications, or
    • other prescription medications except the permitted concomitant medications listed below
  • Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.
  • Any of the following events at the time of enrollment:

    • fever (temporal or rectal temperature of ≥100.4°F), or
    • upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
    • nasal congestion significant enough to interfere with successful inoculation, or
    • otitis media
    • contact with a person diagnosed with COVID-19 disease or active severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection within the preceding 14 days
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 24 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04520659
Other Study ID Numbers  ICMJE CIR 335
Has Data Monitoring Committee Yes
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: Qualified researchers may request access to IPD that underlie results in a publication. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants.
Time Frame: After publication
Access Criteria: Qualified researchers
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Sanofi Pasteur, a Sanofi Company
Investigators  ICMJE
Principal Investigator: Ruth A. Karron, MD Johns Hopkins Bloomberg School of Public Health (JHSPH)
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date August 2020

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