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Safety and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV ΔNS2/Δ1313/I1314L, RSV 6120/ΔNS2/1030s, RSV 276 or Placebo, Delivered as Nose Drops to RSV-Seronegative Children 6 to 24 Months of Age

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ClinicalTrials.gov Identifier: NCT03916185
Recruitment Status : Recruiting
First Posted : April 16, 2019
Last Update Posted : December 10, 2019
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 and immunogenicity of a single dose of the recombinant live-attenuated respiratory syncytial virus (RSV) vaccines, RSV ΔNS2/Δ1313/I1314L, RSV 6120/ΔNS2/1030s, and RSV 276, in RSV-seronegative children 6 to 24 months of age.

Condition or disease Intervention/treatment Phase
Respiratory Syncytial Virus (RSV) Biological: RSV ΔNS2/Δ1313/I1314L Vaccine Biological: RSV 6120/ΔNS2/1030s Vaccine Biological: RSV 276 Vaccine Biological: Placebo Phase 1 Phase 2

Detailed Description:

This study will evaluate the safety and immunogenicity of a single dose of the recombinant live-attenuated respiratory syncytial virus (RSV) vaccines, RSV ΔNS2/Δ1313/I1314L, RSV 6120/ΔNS2/1030s, and RSV 276, in RSV-seronegative children 6 to 24 months of age.

Participants will be randomly assigned to receive a single dose of RSV ΔNS2/Δ1313/I1314L vaccine, RSV 6120/ΔNS2/1030s vaccine, RSV 276 vaccine, or placebo intranasally at study entry.

Participants will be enrolled in the study outside of RSV season. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Phase I/II Study of the Safety and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV ΔNS2/Δ1313/I1314L, RSV 6120/ΔNS2/1030s, RSV 276 or Placebo, Delivered as Nose Drops to RSV-Seronegative Children 6 to 24 Months of Age
Actual Study Start Date : May 16, 2019
Estimated Primary Completion Date : December 10, 2020
Estimated Study Completion Date : April 30, 2021

Arm Intervention/treatment
Experimental: RSV ΔNS2/Δ1313/I1314L Vaccine
Participants will receive a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine at study entry (Day 0).
Biological: RSV ΔNS2/Δ1313/I1314L Vaccine
10^6 plaque-forming units (PFU); administered as nose drops

Experimental: RSV 6120/ΔNS2/1030s Vaccine
Participants will receive a single dose of the RSV 6120/ΔNS2/1030s vaccine at study entry (Day 0).
Biological: RSV 6120/ΔNS2/1030s Vaccine
10^5 plaque-forming units (PFU); administered as nose drops

Experimental: RSV 276 Vaccine
Participants will receive a single dose of the RSV 276 vaccine at study entry (Day 0).
Biological: RSV 276 Vaccine
10^5 plaque-forming units (PFU); 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. Frequency of Grade 1 or higher solicited adverse events (AEs) [ Time Frame: Measured through Day 28 ]
    Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and are graded following a protocol-defined grading system for solicited events.

  2. Frequency of Grade 2 or higher lower respiratory illnesses (LRIs) [ Time Frame: Measured through Day 28 ]
    Graded following a protocol-defined grading system for solicited events

  3. Frequency of serious AEs [ Time Frame: Measured through Day 56 ]
    Serious adverse events are defined according to Version 2.0 of the DAIDS EAE Manual.

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


Secondary Outcome Measures :
  1. Frequency of a greater than or equal to 4-fold rise in serum RSV F immunoglobulin G (IgG) [ Time Frame: Measured through Day 56 ]
    Determined from immunologic assays

  2. Titer of serum RSV F IgG [ Time Frame: Measured at the Day 56 Visit ]
    Determined from immunologic assays

  3. Titer of serum RSV-neutralizing antibodies [ Time Frame: Measured at the Day 56 Visit ]
    Determined from immunologic assays

  4. Frequency of RSV-associated medically attended acute respiratory illness (RSV-MAARI) [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
    Graded following a protocol-defined grading system for solicited events

  5. Maximum grade (if more than one illness within a participant) of RSV-MAARI [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
    Graded following a protocol-defined grading system for solicited events

  6. Frequency of RSV-associated medically attended acute lower respiratory illness (RSV-MAALRI) [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
    Graded following a protocol-defined grading system for solicited events

  7. Maximum grade (if more than one illness within a participant) of RSV-MAALRI [ Time Frame: Measured through the last day of the RSV season, which will occur between 5 and 12 months after study entry, depending on when the participant enrolls in the study ]
    Graded following a protocol-defined grading system for solicited events



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.


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Ages Eligible for Study:   6 Months to 25 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.
  • 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 study 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 study product administration.

    • Note: results from specimens collected during screening for any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (National Institute of Allergy and Infectious Diseases [NIAID], National Institutes of Health [NIH]) are acceptable. If study product will not be administered the same day as randomization (see the study protocol), it must be administered no more than 42 days after the screening sample is collected.
  • Growing normally for age in the opinion of the site clinician in the six months prior to enrollment AND has a current height and weight above the 3rd percentile for age and sex per Centers for Disease Control and Prevention (CDC) World Health Organization (WHO) growth standards.
  • Has received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices [ACIP]).
  • Is expected to be available for the duration of the study.
  • If born to an HIV-infected woman, potential participant 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. If potential participant was breastfed by an HIV-infected woman, each of the sampling times noted above must be measured in weeks after the last exposure to breast milk, rather than weeks of age.

Exclusion Criteria:

  • Prior laboratory-confirmed RSV infection.
  • Known or suspected HIV infection or impairment of immunological functions.
  • Receipt of immunosuppressive therapy, including any systemic, 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 enrollment in this trial, previous maternal or pediatric receipt of a licensed or investigational RSV vaccine, or previous maternal or pediatric receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG or RSV monoclonal antibody [mAb]).
  • Any previous anaphylactic reaction.
  • Any known hypersensitivity to any study product component.
  • Heart disease. Note: Potential 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 a person with chronic lung disease, including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, home oxygen use, reactive airway disease or asthma
  • Member of a household that contains, or will contain, an infant who is less than 4 months of age at the enrollment date through Day 14.
  • Member of a household that contains another child/other children who is/are enrolled or is/are scheduled to be enrolled in IMPAACT 2021 on a different date in the same calendar year (i.e., all eligible children from the same household must be enrolled/receive study product on the same date or in different years).
  • 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 Day 0 to 14 of that other child's participation in the study.
  • Member of a household that contains an immunocompromised individual, including, but not limited to:

    • a person who has been diagnosed with cancer and who has received chemotherapy within the 12 months prior to enrollment; or
    • a person living with a solid organ, cord blood, or bone marrow transplant.
  • Shares a daycare room with infants less than 4 months of age, and parent/guardian is unable or unwilling to suspend daycare for 14 days following study product administration.
  • 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 (including but not limited to rhinorrhea, cough, or pharyngitis) or
    • nasal congestion significant enough to interfere with successful study product administration, or
    • otitis media.
    • Note: if participant is randomized and subsequently noted to have any of the above, study product administration must be deferred per the study protocol.
  • Receipt of the following prior to enrollment (start counting backwards with '1' as the day of planned study product administration):

    • 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 study product administration (start counting with '1' as the day of planned study product administration):

    • 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.
  • Born at less than 34 weeks gestation.
  • Born between 34 weeks gestation and 36 weeks and 6 days 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.

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): NCT03916185


Locations
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United States, California
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program Recruiting
La Jolla, California, United States, 92093-0672
Contact: Megan Loughran, B.A.    858-534-9218    meloughran@ucsd.edu   
Usc La Nichd Crs Recruiting
Los Angeles, California, United States, 90089
Contact: Eva A. Operskalski, Ph.D.    323-865-1554    eva@usc.edu   
United States, Colorado
Univ. of Colorado Denver NICHD CRS Recruiting
Aurora, Colorado, United States, 80045
Contact: Emily Barr, C.P.N.P., C.N.M., M.S.N.    720-777-6752    emily.barr@childrenscolorado.org   
United States, Georgia
Emory University School of Medicine NICHD CRS Recruiting
Atlanta, Georgia, United States, 30322
Contact: LaTeshia Thomas-Seaton    404-616-5936    lseaton@emory.edu   
United States, Illinois
Rush Univ. Cook County Hosp. Chicago NICHD CRS Recruiting
Chicago, Illinois, United States, 60612
Contact: Maureen McNichols, R.N., M.S.N., C.C.R.C.    312-572-4541    maureen_mcnichols@rush.edu   
Lurie Children's Hospital of Chicago (LCH) CRS Recruiting
Chicago, Illinois, United States, 60614-3393
Contact: Margaret Ann Sanders, M.P.H.    312-227-8275    msanders@luriechildrens.org   
United States, Maryland
University of Maryland School of Medicine Center for Vaccine Development CRS Recruiting
Baltimore, Maryland, United States, 21201
Contact: Linda Wadsworth    410-706-6156    lwadswor@som.umaryland.edu   
Jhu Cir Crs Recruiting
Baltimore, Maryland, United States, 21205
Contact: Elizabeth Schappell, C.C.R.P., M.S.N., R.N.    410-614-9114    eschappell@jhu.edu   
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS Recruiting
Boston, Massachusetts, United States, 02118
Contact: Debra McLaud, R.N.    617-414-5813    demclaud@bmc.org   
United States, Missouri
The Children's Mercy Hospital CRS Recruiting
Kansas City, Missouri, United States, 64108-4619
Contact: Joanne Thurber, R.N., C.C.R.C.    1-816-234-3076    jthurber@cmh.edu   
Center for Vaccine Development CRS Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Janice M. Tennant, R.N., M.P.H.    314-977-7540    janice.tennant@health.slu.edu   
United States, New York
Jacobi Med. Ctr. Bronx NICHD CRS Recruiting
Bronx, New York, United States, 10461
Contact: Marlene Burey, R.N., M.S.N., P.N.P.    718-918-4783    marlene.burey@nychhc.org   
SUNY Stony Brook NICHD CRS Recruiting
Stony Brook, New York, United States, 11794
Contact: Erin Infanzon    631-444-8832    Erin.Infanzon@stonybrookmedicine.edu   
United States, North Carolina
Duke Vaccine and Trials Unit CRS Recruiting
Durham, North Carolina, United States, 27705
Contact: Lynn S. Harrington, R.N., B.S.N., CCRP    919-620-5353    lynn.harrington@duke.edu   
United States, Ohio
Gamble Center for Clinical Studies CRS Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Michelle P. Dickey, R.N., FNP    513-636-4105    michelle.dickey@cchmc.org   
United States, Texas
Texas Children's Hospital CRS Recruiting
Houston, Texas, United States, 77030-2399
Contact: Chivon D. McMullen-Jackson, B.S.N., A.D.N., R.N.    832-824-1339    cdmcmull@texaschildrens.org   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Chair: Coleen Cunningham, MD Duke University Medical Center (DUMC) Children's Health Center
Study Chair: 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: NCT03916185    
Other Study ID Numbers: IMPAACT 2021
38530 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: April 16, 2019    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie results in the publication, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
Access Criteria:
  • With whom?

    • Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.
  • For what types of analyses?

    • To achieve aims in the proposal approved by the IMPAACT Network.
  • By what mechanism will data be made available?

    • Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

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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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Virus Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs