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

NCT02040831 | Completed Phase 1 DMC

• 1 other identifier: CIR 291
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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 IMPAACT 2000.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

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 but less than 25 months of age at the time of inoculation
• Parent or guardian who demonstrates their understanding of the study, signs the informed consent, and agrees to vaccine administration following detailed explanation of the study
• Seronegative for RSV antibody, defined as a serum RSV neutralizing antibody titer less than 1:40 as determined within 42 days prior to inoculation
• Participant's history has been reviewed and participant has undergone a physical examination indicating that s/he is in good health. Permitted concomitant medications include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including topical steroids, topical antibiotics, and topical antifungal agents.
• Participant has received routine immunizations appropriate for age, administered:
• at least 2 weeks prior to study vaccine inoculation (inactivated and subunit vaccines and rotavirus vaccine) OR
• at least 4 weeks prior to study vaccine inoculation (all other live vaccines)
• Participant is expected to be available for the duration of the study

You may not qualify if:

• Known or suspected impairment of immunological functions, including maternal history of positive HIV test
• Receipt of immunosuppressive therapy including systemic corticosteroids within the past 30 days. NOTE: Topical steroids, topical antibiotics, and topical antifungal medications are acceptable.
• Bone marrow/solid organ transplant recipient
• Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
• Previous immunization with an RSV vaccine
• Previous serious vaccine-associated AE or any anaphylactic reaction
• Known hypersensitivity to any vaccine component
• Lung or heart disease, including any wheezing event or reactive airway disease. NOTE: Participants with clinically insignificant cardiac abnormalities requiring no treatment may be enrolled. Participants who had one episode of wheezing or received bronchodilator therapy for a single episode of illness in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months may be enrolled.
• Member of a household that contains an immunocompromised individual
• Member of a household that contains infants less than 6 months of age
• Attends day care with infants less than 6 months of age, and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization. NOTE: Children who attend facilities that separate children by age and minimize opportunities for transmission of virus through direct physical or aerosol contact are acceptable.
• Participant has a rectal temperature of greater than or equal to 100.4°F on the day of planned vaccination, or URI (rhinorrhea, cough, or pharyngitis) or nasal congestion significant enough to interfere with successful vaccination, or otitis media
• Participant has received any killed vaccine or live attenuated rotavirus vaccine within the last 2 weeks, any other live vaccine within the last 4 weeks, or gamma globulin (or other antibody products) within the past 3 months
• Receipt of another investigational vaccine or investigational drug within the prior 28 days of receiving the study inoculation
• Participant has received antibiotics or systemic or nasal steroid therapy for acute illness within the previous 3 days prior to vaccination. NOTE: Permitted concomitant medications include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) topical steroids, topical antibiotics, and topical antifungal agents.

Sponsors & Collaborators

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

Study Sites (1)

Center for Immunization Research, JHU

Baltimore, Maryland, 21205, 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

• Ruth A. Karron, MD

  Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)

  PRINCIPAL INVESTIGATOR

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: January 17, 2014
• First Posted: January 20, 2014
• Study Start: September 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: December 21, 2016

Record last verified: 2016-12

Locations

US (1)