Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluating the Infectivity, Safety, and Immunogenicity of the Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants 6 to 24 Months of Age

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: NCT03227029
Recruitment Status : Completed
First Posted : July 24, 2017
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE July 20, 2017
First Posted Date  ICMJE July 24, 2017
Last Update Posted Date October 14, 2020
Actual Study Start Date  ICMJE August 4, 2017
Actual Primary Completion Date December 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2017)
  • Grades of study product-related solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]
    May include fever, acute otitis media, upper respiratory tract illness (URI), or lower respiratory tract illness (LRI)
  • Grades of study product-related unsolicited AEs [ Time Frame: Measured through Day 28 ]
    Defined as all other AEs that are not solicited AEs
  • Grades of study product-related serious adverse events (SAEs) [ Time Frame: Measured through Day 56 ]
    SAEs as defined in the protocol
  • Number of participants infected 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 this time period; Day 0 nasal wash will be counted as baseline) and/or 2) greater than or equal to 4-fold rise in RSV serum neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 56
  • Peak titer of vaccine virus shed [ Time Frame: Measured through Day 28 ]
    Determined from virologic assays
  • Duration of virus shedding in nasal washes [ Time Frame: Measured through Day 28 ]
    As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
  • Frequency of a greater than or equal to 4-fold rise in RSV serum neutralizing antibody titer [ Time Frame: Measured through Day 56 ]
    Determined from virologic and immunologic assays
  • Frequency of RSV neutralizing antibody responses [ Time Frame: Measured through Day 56 ]
    Assessed by 60% RSV plaque reduction neutralization assay at study entry and Study Day 56
  • Frequency of a greater than or equal to 4-fold rise in serum antibody titers to RSV F glycoprotein [ Time Frame: Measured through Day 56 ]
    Assessed by ELISA
  • Frequency of antibody responses to RSV F glycoprotein [ Time Frame: Measured through Day 56 ]
    Assessed by ELISA
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2018)
  • Frequency of symptomatic, medically attended respiratory and febrile illness AEs in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured through Month 12 ]
    Illness graded by severity based on clinical assessments
  • Frequency 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 Month 13 ]
    Determined from virologic and immunologic assays
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2017)
  • Frequency of symptomatic, medically attended respiratory and febrile illness AEs in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured through Month 12 ]
    Illness graded by severity based on clinical assessments
  • Frequency 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 Month 13 ]
    Determined from virologic and immunologic assays
  • Frequency of B cell response to vaccine [ Time Frame: Measured through Month 13 ]
    Determined from virologic and immunologic assays
  • Frequency of mucosal antibody responses to vaccine [ Time Frame: Measured through Month 13 ]
    Determined from nasal wash or nasosorption samples
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 the Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants 6 to 24 Months of Age
Official Title  ICMJE 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
Brief 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.

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 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.

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 Respiratory Syncytial Virus Infections
Intervention  ICMJE
  • Biological: RSV ΔNS2/Δ1313/I1314L
    10^6 plaque-forming units (PFU); administered as nose drops
  • Biological: RSV 276
    10^5 PFU; administered as nose drops
  • Biological: Placebo
    Administered as nose drops
Study Arms  ICMJE
  • Experimental: RSV ΔNS2/Δ1313/I1314L vaccine
    Participants will receive a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0).
    Intervention: Biological: RSV ΔNS2/Δ1313/I1314L
  • Experimental: RSV 276 vaccine
    Participants will receive a single dose of the RSV 276 vaccine at study entry (Day 0).
    Intervention: Biological: RSV 276
  • Placebo Comparator: 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 Completed
Actual Enrollment  ICMJE
 (submitted: October 12, 2020)
65
Original Estimated Enrollment  ICMJE
 (submitted: July 20, 2017)
80
Actual Study Completion Date  ICMJE October 1, 2020
Actual Primary Completion Date December 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

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.
  • 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/mm^3. 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/mm^3 (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/mm^3 (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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 24 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03227029
Other Study ID Numbers  ICMJE IMPAACT 2018
38405 ( Registry Identifier: DAIDS-ES Registry Number )
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 Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Coleen Cunningham, MD Children's Health Center, DUMC
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date October 2020

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