Summary

for people ages 6 months to 24 months (full criteria)
healthy people welcome
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of the recombinant live-attenuated respiratory syncytial virus (RSV) vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 or placebo when delivered as nose drops to RSV-seronegative infants 6 to 24 months of age. This study is a companion study to CIR 321.

Official Title

Randomized Phase I Study of the Infectivity, Safety, and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 or Placebo, Delivered as Nose Drops to RSV-Seronegative Infants 6 to 24 Months of Age

Details

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 the infectivity, safety, and immunogenicity of two recombinant live-attenuated RSV vaccines: RSV ΔNS2/Δ1313/I1314L and RSV 276. The vaccines will be delivered as nose drops to RSV-seronegative infants 6 to 24 months of age.

Participants will be randomly assigned to receive a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine, the RSV 276 vaccine, or placebo at study entry (Day 0).

Participants will be enrolled in the study outside of RSV season, i.e., between April 1 and October 14 for most sites or—for sites with local RSV seasons that start earlier—as specified on a site-by-site basis in the manual of procedures (MOP). All participants will remain on study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment (this window applies to all sites). Participants' total study duration is between 6 and 13 months, depending on when they enroll in the study. Participants will attend several study visits throughout the study, which may include physical examinations, blood collection, nasal washes, and nasal adsorption (nasosorption) specimen collection. Participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.

Keywords

Respiratory Syncytial Virus Infections Virus Diseases Vaccines RSV ΔNS2/Δ1313/I1314L RSV 276 RSV ΔNS2/Δ1313/I1314L vaccine RSV 276 vaccine

Eligibility

You can join if…

Open to people ages 6 months to 24 months

  • Greater than or equal to 6 months (defined as greater than or equal to 180 days) of age at the time of screening and less than 25 months (defined as less than 750 days)of age at the time of enrollment
  • In good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.
  • Parent/guardian is willing and able to provide written informed consent as described in the protocol.
  • 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. Note: results from specimens collected during screening for any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (NIAID, NIH)are acceptable as long as within the 42-day window.
  • Growing normally for age (i.e., not downwardly crossing two major centiles on a standard growth chart) in the six months prior to enrollment 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.
  • Has received routine immunizations appropriate for age (as per national Center for

Disease Control Advisory Committee on Immunization Practices [ACIP]). Note: if rotavirus immunization was delayed, "catch-up" rotavirus immunization is indicated only if the participant is age-eligible per ACIP.

  • Is expected to be available for the duration of the study.
  • If born to an HIV-infected woman, participant must not have been breastfed and must have documentation of 2 negative HIV nucleic acid (RNA or DNA) test results from samples collected on different dates with both collected when greater than or equal to 4 weeks of age and at least one collected when greater than or equal to 16 weeks of age, and no positive HIV nucleic acid (RNA or DNA) test; or 2 negative HIV antibody tests, both from samples collected at greater than or equal to 24 weeks of age.

You CAN'T join if...

  • 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.
  • Any receipt of bone marrow/solid organ transplant.
  • Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities.
  • Previous receipt of a licensed or investigational RSV vaccine (or 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).
  • Any previous anaphylactic reaction.
  • Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if grading is not possible, determine if the reaction was considered severe or life threatening; if so, it is exclusionary.
  • Any 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 diagnosed 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/other children who is/are, or is/are scheduled to be, enrolled in IMPAACT 2018 AND the date of enrollment to IMPAACT 2018 will not be concurrent with the other participant(s) living in the household (i.e.,all eligible children from the same household must be enrolled on the same date).
  • Member of a household that contains another child who is, or is scheduled to be,enrolled in another study evaluating an intranasal live-attenuated RSV vaccine, 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 greater than or equal to 6 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count less than 300 cells/mm3. CD4 T lymphocyte count must have been measured within 6 months prior to enrollment for individuals with detectable virus or within 12 months prior to enrollment for individuals with undetectable virus, or

  • a person age 1 year up to less than 6 years with HIV-related immunodeficiency,defined as having a most recent CD4 T lymphocyte cell percentage less than 25 or CD4 T lymphocyte count less than 750 cells/mm3 (if both values are available,use the lower of the two). CD4 T lymphocyte parameter must have been measured within the 6 months prior to enrollment; or

  • a person age less than 1 year with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 30 or CD4 T lymphocyte count less than 1000 cells/mm3 (if both values are available, use the lower of the two). CD4 T lymphocyte parameter must have been measured within the 6 months prior to enrollment; or

  • a person who has received chemotherapy within the 12 months prior to enrollment;or
  • a person receiving immunosuppressant agents; or
  • a person living with a solid organ or bone marrow transplant.
  • Documenting the verbal report of CD4 T cell lymphocyte count is sufficient if the parent/guardian is confident of history. Individually identifiable information(e.g., name) pertaining to members of the household will not be collected or recorded. Confirmatory laboratory tests for members of the household will not be ordered or collected.
  • 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 (rectal temperature of greater than or equal to 100.4°F (38°C)), 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 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
  • Scheduled administration 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 immunoglobulin, any antibody products, or any blood products within the past 6 months prior to enrollment
  • Receipt of any of the following medications within 3 days prior to 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
  • 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.
  • Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days prior to enrollment.
  • 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.
  • Current suspected or documented developmental disorder, delay, or other developmental problem.
  • Any previous receipt of supplemental oxygen therapy in a home setting.

Locations

  • University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program accepting new patients
    La Jolla California 92093-0672 United States
  • Usc La Nichd Crs accepting new patients
    Los Angeles California 90089 United States
  • David Geffen School of Medicine at UCLA NICHD CRS accepting new patients
    Los Angeles California 90095-1752 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT03227029
Phase
Phase 1
Study Type
Interventional
Last Updated
April 24, 2018