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

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ClinicalTrials.gov Identifier: NCT03102034
Recruitment Status : Active, not recruiting
First Posted : April 5, 2017
Last Update Posted : October 26, 2017
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 CIR 313.


Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus Infections Biological: D46/NS2/N/ΔM2-2-HindIII 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 the safety, infectivity, and immunogenicity of a single dose of RSV D46/NS2/N/ΔM2-2-HindIII, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.

Participants will be randomly assigned to receive a single dose of the D46/NS2/N/ΔM2-2-HindIII 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 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. Participants' total study duration will be 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, and nasal washes. Participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 6 to 24 Months of Age
Actual Study Start Date : March 30, 2017
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: RSV D46/NS2/N/ΔM2-2-HindIII Vaccine
Participants will receive a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0).
Biological: D46/NS2/N/ΔM2-2-HindIII
10^5 plaque-forming units (PFU) per 0.5ml vaccine; 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, acute otitis media, upper respiratory tract illness (URI), or lower respiratory tract 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 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 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 ]
    As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)

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

  8. Frequency of antibody responses to RSV F glycoprotein [ Time Frame: Measured through Day 56 ]
    Assessed by ELISA at study entry and Study Day 56


Secondary Outcome Measures :
  1. Frequency of symptomatic, medically attended respiratory and febrile illness in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season [ Time Frame: Measured up through Month 12 ]
    Illness graded by severity based on clinical assessments

  2. 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 up through Month 13 ]
    Determined from virologic and immunologic assays

  3. Frequency of B cell responses to vaccine [ Time Frame: Measured up through Month 13 ]
    Determined from virologic and immunologic assays

  4. Frequency of mucosal antibody responses to vaccine [ Time Frame: Measured up through Month 13 ]
    Determined from nasal wash samples



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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 (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
  • The 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 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.
  • 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 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.
  • Participant 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.
  • 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 placebo in any IMPAACT RSV study) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV immunoglobulin [IG] or RSV monoclonal antibody [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 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 who is, or is scheduled to be, enrolled in IMPAACT 2011, 2012 or 2013 or 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, 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.
    • Verbal report of CD4 T cell lymphocyte is sufficient documentation if the parent/guardian is confident of history.
  • 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
  • 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

      • 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.
  • 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): NCT03102034


Locations
United States, California
Usc La Nichd Crs
Los Angeles, California, United States, 90089
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, United States, 90095-1752
United States, Colorado
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University School of Medicine NICHD CRS
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States, 60612
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, United States, 60614-3393
United States, Maryland
Johns Hopkins University Center for Immunization Research
Baltimore, Maryland, United States, 21205
United States, New York
SUNY Stony Brook NICHD CRS
Stony Brook, New York, United States, 11794
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, United States, 10461
United States, Tennessee
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, United States, 38105-3678
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Elizabeth (Betsy) J. McFarland, MD Children's Hospital Colorado Pediatric Infectious Diseases

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03102034     History of Changes
Other Study ID Numbers: IMPAACT 2013
30074 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: April 5, 2017    Key Record Dates
Last Update Posted: October 26, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Virus Diseases
Respiratory Syncytial Virus Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs