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Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants and Children 6 to 24 Months of Age

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ClinicalTrials.gov Identifier: NCT03099291
Recruitment Status : Completed
First Posted : April 4, 2017
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

The purpose of this study is to evaluate the safety, infectivity, and immunogenicity of a single dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants and children 6 to 24 months of age.

This study is a companion study to IMPAACT 2013.


Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Biological: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine Biological: Placebo Phase 1

Detailed Description:

Human respiratory syncytial virus (RSV) is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age worldwide. This study will evaluate whether D46/NS2/N/ΔM2-2-HindIII vaccine is attenuated and immunogenic in children 6 to 24 months of age.

Participants will be randomly assigned to receive a single dose of the RSV D46/NS2/N/ΔM2-2-HindIII vaccine or placebo at study entry (Day 0).

Participants will be enrolled in the study between April 1 and October 31 (outside of RSV season) and will remain on 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 will be between 6 and 13 months, depending on when they enroll in the study. Participants will be evaluated in study visits that may include physical examinations, blood collection, and nasal washes. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double Blind
Primary Purpose: Prevention
Official Title: Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, D46/NS2/N/ΔM2-2-HindIII, Lot RSV#011B, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
Actual Study Start Date : April 1, 2017
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
Participants will receive a single dose of the RSV D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
Biological: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
10^5 plaque-forming units (PFUs); administered as nose drops

Placebo Comparator: Placebo
Participants will receive a single dose of placebo at study entry (Day 0).
Biological: Placebo
Administered as nose drops




Primary Outcome Measures :
  1. Grades of study product-related solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]
    May include fever, upper respiratory illness (URI), otitis media, or lower respiratory illness (LRI)

  2. Grades of study product-related unsolicited AEs [ Time Frame: Measured through Day 28 ]
    Defined as all other AEs that are not solicited AEs

  3. Grades of study product-related serious adverse events (SAEs) [ Time Frame: Measured through Day 56 ]
    SAEs as defined in the protocol

  4. Number of participants with infection with vaccine virus [ Time Frame: Measured through Day 56 ]
    Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) and/or 2) greater than or equal to 4-fold rise in RSV neutralizing antibody titer from Study Day 0-56

  5. Peak titer of vaccine virus shed [ Time Frame: Measured through Day 28 ]
    Determined from virologic assays

  6. Duration of vaccine virus shedding in nasal washes [ Time Frame: Measured through Day 28 ]
    Determined by a) culture and b) RT-PCR from Study Day 0-28

  7. Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer [ Time Frame: Measured through Day 56 ]
    Determined from virologic and immunologic assays

  8. Antibody responses to RSV F glycoprotein [ Time Frame: Measured through Day 56 ]
    As assessed by enzyme-linked immunosorbent assay (ELISA)


Secondary Outcome Measures :
  1. Frequency of symptomatic, medically attended respiratory and febrile illness in the vaccine and placebo recipients who experience natural infection with wild-type RSV during the subsequent RSV season [ Time Frame: Measured through study completion, an average of 12 months ]
    Will be measured through the subsequent RSV season (November 1 in the calendar year of study entry to March 31 in the calendar year following study entry)

  2. Measurement of antibody responses in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured through study completion, an average of 13 months ]
    Will be measured at the post-RSV season visit (between April 1 and April 30 in the calendar year following study entry)

  3. Frequency of B cell responses to vaccine [ Time Frame: Measured through study completion, an average of 13 months ]
    Will be measured at the post-RSV season visit (between April 1 and April 30 in the calendar year following study entry)



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Greater than or equal to 6 months (greater than or equal to 180 days) of age at the time of screening and less than 25 months (less than 750 days) of age
  • Participant is in good health based on review of the medical record, history, and physical examination, without evidence of chronic disease
  • Parents/guardians are willing and able to provide written informed consent
  • Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening from a sample collected no more than 42 days prior to inoculation
  • Is growing at a normal velocity for age as demonstrated on a standard growth chart AND

    • If less than 1 year of age: has a current height and weight above the 5th percentile
    • If 1 year of age or older: has a current height and weight above the 3rd percentile for age
  • Participant has received routine immunizations appropriate for age (as per Center for Disease Control Advisory Committee on Immunization Practices [ACIP])
  • Participant is expected to be available for the duration of the study

Exclusion Criteria:

  • Known or suspected HIV infection or impairment of immunological functions
  • Receipt of immunosuppressive therapy, including any systemic, including either nasal or inhaled, corticosteroids within 28 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.
  • Bone marrow/solid organ transplant recipient
  • Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities
  • Previous receipt of a licensed or investigational RSV vaccine or receipt of placebo in any IMPAACT RSV study or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV Ig or RSV mAb)
  • Previous anaphylactic reaction
  • Previous vaccine-associated adverse reaction that was Grade 3 or above
  • Known hypersensitivity to any study product component
  • Heart disease. Note: Participants with cardiac abnormalities documented to be clinically insignificant and requiring no treatment may be enrolled
  • Lung disease, including any history of reactive airway disease or medically documented wheezing
  • Member of a household that contains, or will contain, an infant who is less than 6 months of age at the enrollment date through Day 28
  • Member of a household that contains another child who is, or is scheduled to be, enrolled in CIR 311, 312 or 313 AND there has been or will be an overlap in residency during that other child's participation in the study's Acute Phase (Days 0 to 28)
  • Member of a household that contains an immunocompromised individual, including but not limited to:

    • a person who is HIV infected
    • a person who has received chemotherapy within the 12 months prior to enrollment
    • a person receiving immunosuppressant agents
    • a person living with a solid organ or bone marrow transplant
  • Attends a daycare facility and shares a room with infants less than 6 months of age, and parent/guardian is unable or unwilling to suspend daycare for 28 days following inoculation
  • Any of the following events at the time of enrollment:

    • fever (temporal or rectal temperature of greater than or equal to 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
  • Receipt of the following prior to enrollment:

    • any killed 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
  • Scheduled administration of the following after planned inoculation:

    • killed 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 immunoglobulin, any antibody products, or any blood products within the past 6 months
  • 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 medication except as listed below
  • Receipt of salicylate (aspirin) or salicylate-containing products within the past 28 days
  • Born at less than 34 weeks gestation
  • Born at less than 37 weeks gestation and less than 1 year of age at the time of enrollment
  • Suspected or documented developmental disorder, delay, or other developmental problem
  • Previous receipt of supplemental oxygen therapy in a home setting

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03099291


Locations
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United States, Maryland
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, United States, 21205
Center for Immunization Research East, Johns Hopkins Bayview Medical Center Campus
Baltimore, Maryland, United States, 21224
Center for Immunization Research South
Laurel, Maryland, United States, 20708
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Ruth Karron, MD Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03099291     History of Changes
Other Study ID Numbers: CIR 313
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Syncytial Virus Infections
Virus Diseases
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs