Safety and Immune Response to a Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children

NCT02237209 | Completed Phase 1 DMC

• 2 other identifiers: IMPAACT 2000DAIDS ES
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 7

Brief Summary

Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around the world. This study will evaluate the safety and immune response to an RSV vaccine in RSV-seronegative infants and children. This study is a companion study to CIR 291.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (4)

• Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study, the first 28 days after inoculation

  Measured through Day 28

• Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study, the first 28 days after inoculation

  Measured through Day 28

• Frequency of vaccine-related lower respiratory illness

  Measured through Day 56

• Proportion of participants that develop 4-fold or greater rises in RSV-neutralizing antibody titer following vaccination

  Antibody responses to the RSV F glycoprotein will also be assessed by enzyme-linked immunosorbent assay (ELISA).

  Measured through Day 56

Study Arms (2)

RSV LID ΔM2-2 Vaccine

EXPERIMENTAL

Participants will receive one dose of the RSV LID ΔM2-2 vaccine at study entry, delivered as nose drops.

Biological: RSV LID ΔM2-2 Vaccine

Placebo Vaccine

PLACEBO COMPARATOR

Participants will receive one dose of placebo at study entry, delivered as nose drops.

Biological: Placebo Vaccine

Interventions

RSV LID ΔM2-2 Vaccine BIOLOGICAL

10\^5.0 plaque forming units (PFU); 0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)

RSV LID ΔM2-2 Vaccine

Placebo Vaccine BIOLOGICAL

0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)

Placebo Vaccine

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participant is at least 6 months (defined as at least 180 days) of age at the time of screening and less than 25 months (defined as less than 750 days) of age
• Participant is in good health based on review of the medical record, history, and physical examination, without evidence of chronic disease. Note: any questions regarding interpretation of this criterion should be forwarded to the team.
• Parents/guardians demonstrate their understanding of the study, sign the informed consent, and agree to administration of study product following a detailed explanation of the study
• Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening obtained no more than 42 days prior to scheduled inoculation
• Has a current height and weight above the 5th percentile for age
• Participant has received routine immunizations appropriate for age. Prior vaccines were administered at least:
• weeks prior to enrollment for inactivated and subunit vaccines and rotavirus vaccine, and
• weeks prior to enrollment for all other live vaccines.
• Participant is expected to be available for the duration of the study
• If born to an HIV-infected woman, participant must be non-breastfeeding with documentation of two negative HIV nucleic acid (RNA or DNA) tests with both collected when at least 1 month of age and at least one collected when at least 4 months of age, and no positive HIV nucleic acid (RNA or DNA) test; or two negative HIV antibody tests, both collected at less than or equal to 6 months of age

You may not qualify if:

• Known or suspected HIV infection or impairment of immunological functions
• 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) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG)
• Previous vaccine-associated anaphylactic or other severe adverse vaccine reaction
• 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 wheezing or reactive airway disease
• 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 2000, 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 5 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count less than 300/mcL. CD4 T lymphocyte count must have been measured within 6 months prior to enrollment; or
• a person less than 5 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 15. CD4 T lymphocyte percentage 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.
• Verbal report of CD4 T cell lymphocyte is sufficient documentation if the parent/guardian is confident of history.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

Usc La Nichd Crs

Alhambra, California, 91803, United States

Location

University of California, UC San Diego CRS

La Jolla, California, 92093-0672, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, 60614-3393, United States

Location

Johns Hopkins University Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, 38105-3678, United States

Location

Related Publications (1)

• McFarland EJ, Karron RA, Muresan P, Cunningham CK, Valentine ME, Perlowski C, Thumar B, Gnanashanmugam D, Siberry GK, Schappell E, Barr E, Rexroad V, Yogev R, Spector SA, Aziz M, Patel N, Cielo M, Luongo C, Collins PL, Buchholz UJ; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2000 Study Team. Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children. J Infect Dis. 2018 Apr 11;217(9):1347-1355. doi: 10.1093/infdis/jiy040.

  PMID: 29509911 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Elizabeth McFarland, MD

  Children's Hospital Colorado

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2014
• First Posted: September 11, 2014
• Study Start: September 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: October 8, 2015

Record last verified: 2015-10

Locations

US (7)