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Evaluating the Safety and Immune Response to a Single Dose of a Respiratory Syncytial Virus (RSV) Vaccine in Infants and Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01893554
First received: July 2, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

Human respiratory syncytial virus (RSV) is a common cause of respiratory illness in infants and children around the world. This study will evaluate the safety and immune response to a RSV vaccine in two groups of participants: healthy children who have already had an RSV infection (RSV seropositive) and healthy infants and children who have not already had an RSV infection (RSV seronegative).


Condition Intervention Phase
Respiratory Syncytial Virus Infections
Biological: RSV ΔNS2 Δ1313 I1314L Vaccine
Biological: Placebo (1x Leibovitz L-15 medium)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase I Study of the Safety and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine RSV ΔNS2 Δ1313 I1314L, Lot RSV#006A, Delivered as Nose Drops to RSV-Seropositive Children 12 to 59 Months of Age and RSV-Seronegative Infants and Children 6 to 24 Months of Age

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency and severity of vaccine-related solicited adverse events (AEs) that occur during the intensive monitoring phase of the study [ Time Frame: Measured at Days 0-10 for seropositive children and Days 0-28 for seronegative infants and children ] [ Designated as safety issue: Yes ]
  • Proportion of participants that develop 4-fold or greater rises in RSV neutralizing antibody titer following vaccination [ Time Frame: Measured through follow-up period, up to 1 year after study entry ] [ Designated as safety issue: No ]
    Antibody responses to the RSV F glycoprotein will also be assessed by enzyme-linked immunosorbent assay (ELISA).


Estimated Enrollment: 75
Study Start Date: June 2013
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: RSV vaccine
Healthy RSV-seropositive children ages 12 to 59 months will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.
Biological: RSV ΔNS2 Δ1313 I1314L Vaccine

For participants in Groups 1 and 3: 10^6 plaque forming units (PFU) of RSV ΔNS2 Δ1313 I1314L vaccine will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

For participants in Group 2: 10^5 PFU of RSV ΔNS2 Δ1313 I1314L vaccine will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

Placebo Comparator: Group 1: Placebo
Healthy RSV-seropositive children ages 12 to 59 months will receive one dose of the placebo administered as nose drops at study entry.
Biological: Placebo (1x Leibovitz L-15 medium)
Placebo will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).
Experimental: Group 2: RSV vaccine
Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.
Biological: RSV ΔNS2 Δ1313 I1314L Vaccine

For participants in Groups 1 and 3: 10^6 plaque forming units (PFU) of RSV ΔNS2 Δ1313 I1314L vaccine will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

For participants in Group 2: 10^5 PFU of RSV ΔNS2 Δ1313 I1314L vaccine will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

Placebo Comparator: Group 2: Placebo
Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the placebo administered as nose drops at study entry.
Biological: Placebo (1x Leibovitz L-15 medium)
Placebo will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).
Experimental: Group 3: RSV vaccine
Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the RSV ΔNS2 Δ1313 I1314L vaccine administered as nose drops at study entry.
Biological: RSV ΔNS2 Δ1313 I1314L Vaccine

For participants in Groups 1 and 3: 10^6 plaque forming units (PFU) of RSV ΔNS2 Δ1313 I1314L vaccine will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

For participants in Group 2: 10^5 PFU of RSV ΔNS2 Δ1313 I1314L vaccine will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

Placebo Comparator: Group 3: Placebo
Healthy RSV-seronegative infants and children ages 6 to 24 months will receive one dose of the placebo administered as nose drops at study entry.
Biological: Placebo (1x Leibovitz L-15 medium)
Placebo will be administered as nose drops (0.25 mL per nostril for a total of 0.5 mL).

Detailed Description:

RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age around the world. RSV illness can range from mild upper respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia. The purpose of this study is to evaluate the safety and immunogenicity of a single dose of a RSV vaccine in healthy children. Study researchers will first evaluate the vaccine in healthy RSV-seropositive children and will then evaluate the vaccine in healthy RSV-seronegative infants and children.

This study will first enroll healthy RSV-seropositive children ages 12 to 59 months (Group 1). At study entry, participants will undergo a medical history review, physical examination, blood collection, and a nasal wash procedure. Participants will be randomly assigned to receive either the RSV vaccine or placebo vaccine, administered as nose drops. Subjects will be actively monitored for 28 days following administration of vaccine or placebo; monitoring will include medical history reviews, clinical assessments, and at some visits, nasal washes. On the days where no study visit is scheduled, study researchers will contact participants' parents or guardians for medical follow-up.

Study researchers will evaluate the study data of participants in Group 1 before enrolling participants in Group 2, and study data from Group 2 will be reviewed before enrolling participants in Group 3. Participants in Groups 2 and 3 will include healthy RSV-seronegative infants and children ages 6 to 24 months. These participants will also be randomly assigned to receive either the RSV vaccine or placebo vaccine, administered as nose drops. Subjects will be actively monitored for 56 days following administration of vaccine or placebo; monitoring will include medical history reviews, clinical assessments, and at some visits, nasal washes. On the days where no study visit is scheduled, study researchers will contact participants' parents or guardians for medical follow-up. At a study visit on Day 56, participants will undergo a medical history review, blood collection, and a nasal wash procedure.

For participants in Groups 2 and 3, from November through March following each participant's vaccination visit, parents or guardians will monitor participants for RSV-associated illnesses and report these on a weekly basis via telephone calls to study researchers. Participants may have additional study visits that may include blood collection and/or nasal wash procedures during this follow-up period.

  Eligibility

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for Seropositive Children:

  • Healthy children 12 to 59 months of age, whose parent/guardian understands and signs the study informed consent and who agrees to vaccine administration following a detailed explanation of the study
  • Seropositive for RSV as defined by serum RSV neutralizing antibody titer equal to or greater than 1:40. If a child between 12 and 59 months of age is determined to be RSV seropositive prior to Day 56, s/he does not need an additional screening serum specimen, but a pre-inoculation serum specimen must be obtained.
  • Participant's history has been reviewed and participant has undergone a physical examination indicating that s/he is in good health
  • Participant is expected to be available for the duration of the study

Exclusion Criteria for Seropositive Children:

  • Known or suspected impairment of immunological functions, including maternal history of positive HIV test, receiving immunosuppressive therapy including systemic corticosteroids, or bone marrow/solid organ transplant recipients (topical steroids, topical antibiotics, and topical antifungal medications are acceptable)
  • Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
  • Previous immunization with an RSV vaccine
  • Previous serious vaccine-associated AE or anaphylactic reaction
  • Known hypersensitivity to any vaccine component
  • Lung or heart disease, including any wheezing event or reactive airway disease. Participants with clinically insignificant cardiac abnormalities requiring no treatment may be enrolled. Participants who had one episode of wheezing or received bronchodilator therapy for a single episode of illness in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months may also be enrolled.
  • Member of a household that includes an immunocompromised individual or infants less than 6 months of age, other than a study participant
  • Attends day care with infants less than 6 months of age, and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization. Note: children who attend facilities that separate children by age and minimize opportunities for transmission of virus through direct physical or aerosol contact are acceptable.

Inclusion Criteria for Seronegative Infants and Children:

  • Healthy children 6 to 24 months of age whose parents/guardians can understand and sign the informed consent and who agree to vaccine administration following detailed explanation of the study
  • Seronegative for RSV antibody, defined as a serum RSV neutralizing antibody titer less than 1:40 as determined within 30 days prior to inoculation
  • Participant's history has been reviewed and participant has undergone a physical examination indicating that s/he is in good health. Permitted concomitant medications include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including topical steroids, topical antibiotics, and topical antifungal agents.
  • Participant is expected to be available for the duration of the study

Exclusion Criteria for Seronegative Infants and Children:

  • Known or suspected impairment of immunological functions, including maternal history of positive HIV test, receiving immunosuppressive therapy including systemic corticosteroids, or bone marrow/solid organ transplant recipients
  • Major congenital malformations including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
  • Previous immunization with an RSV vaccine
  • Previous serious vaccine-associated AE or anaphylactic reaction
  • Known hypersensitivity to any vaccine component
  • Lung or heart disease, including any wheezing event or reactive airway disease. Participants with clinically insignificant cardiac abnormalities requiring no treatment may be enrolled. Participants who had one episode of wheezing or received bronchodilator therapy for a single episode of illness in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months may also be enrolled.
  • Member of a household that includes an immunocompromised individual or infants less than 6 months of age
  • Attends daycare with infants less than 6 months of age, and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization. Children who attend facilities that separate children by age and minimize opportunities for transmission of virus through direct physical or aerosol contact are acceptable.

Temporary Exclusion Criteria for Seropositive and Seronegative Children:

The following are temporary or self-limiting conditions, and once resolved, the child may be enrolled, if otherwise eligible. If the period of temporary exclusion is greater than 30 days, seronegative children will need to be rescreened for levels of RSV neutralizing antibody.

  • Fever (rectal temperature of greater than or equal to 100.4°F [38°C]), or upper respiratory illness (rhinorrhea, cough, or pharyngitis) or nasal congestion significant enough to interfere with successful vaccination, or otitis media
  • Has received any killed vaccine or live attenuated rotavirus vaccine within the last 2 weeks, any other live vaccine within the last 4 weeks, or gamma globulin (or other antibody products) within the past 3 months
  • Receipt of another investigational vaccine or investigational drug within 28 days of receiving this investigational RSV vaccine
  • Has received antibiotics or systemic or nasal steroid therapy for acute illness within the previous 3 days prior to vaccination (steroid skin creams or lotions and topical antibiotics or antifungal preparations are permitted)
  • Has received salicylate (aspirin) or salicylate-containing products within the past month
  • Infants born at less than 37 weeks gestation and less than 1 year of age
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01893554

Contacts
Contact: Jocelyn San Mateo 410-614-4306 jsanmate@jhsph.edu

Locations
United States, Maryland
Center for Immunization Research (CIR) Recruiting
Baltimore, Maryland, United States, 21205
Contact    410-502-3333      
Center for Immunization Research South Recruiting
Laurel, Maryland, United States, 20708
Contact    301-490-3767      
Sponsors and Collaborators
Investigators
Principal Investigator: Ruth A. Karron, MD Johns Hopkins Bloomberg School of Public Health
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01893554     History of Changes
Other Study ID Numbers: CIR 288, CIR 288
Study First Received: July 2, 2013
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Respiratory Syncytial Virus Infections
Virus Diseases
Mononegavirales Infections
Paramyxoviridae Infections
Pneumovirus Infections
RNA Virus Infections

ClinicalTrials.gov processed this record on November 27, 2014