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

NCT ID: NCT02040831

Last Updated: 2016-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2015-04-30

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.

Detailed Description

RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age in the world. RSV illness can range from mild upper respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia. Severe RSV disease in infancy may also predispose children to develop reactive airway disease during childhood. The purpose of this study is to evaluate the safety and immunogenicity of an RSV vaccine (RSV LID ΔM2-2) in RSV-seronegative infants and children at least 6 months and through 24 months of age.

To determine study eligibility, the screening process will include a blood collection. At study entry, eligible participants will be randomly assigned to receive one dose of either the RSV vaccine or placebo, which will be delivered as nose drops. Participants will also undergo a review of medical history, clinical assessment, and a nasal wash. They will then receive their assigned vaccine and will remain under observation for monitoring for 30 minutes after receiving the vaccine. Additional study visits will occur at Days 3, 5, 7, 10, 12, 14, 17, 19, 21, 28, and 56. These visits will include clinical assessments and nasal washes; on Day 56, a blood collection will also occur. On days where no study visit is scheduled (through Day 27), participants' parents or guardians will report participants' temperatures and signs of illness to researchers by e-mail or phone.

In October following vaccination, participants may have a pre-RSV season blood collection visit. During RSV season, November through March following vaccination, researchers will contact participants' parents or guardians on a weekly basis for follow-up monitoring. During this time frame, participants seen by a medical provider for fever, respiratory illness, or otitis media will have a study visit, which will include a nasal wash and clinical assessment. In April following vaccination, participants will undergo a final blood collection.

Conditions

Respiratory Syncytial Virus Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

RSV LID ΔM2-2 Vaccine

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

Group Type: EXPERIMENTAL

RSV LID ΔM2-2 Vaccine

Intervention Type: BIOLOGICAL

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

Placebo Vaccine

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

Group Type: PLACEBO_COMPARATOR

Placebo Vaccine

Intervention Type: BIOLOGICAL

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

Interventions

RSV LID ΔM2-2 Vaccine

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

Intervention Type: BIOLOGICAL

Placebo Vaccine

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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:

1. at least 2 weeks prior to study vaccine inoculation (inactivated and subunit vaccines and rotavirus vaccine) OR

2. 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

Exclusion Criteria

• 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.

The following are temporary or self-limiting conditions. Once resolved, the participant may be enrolled, if otherwise eligible, and if the period of temporary exclusion has been less than 42 days from screening. Otherwise, the participant will need to be rescreened.

• 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.
• Participant has received salicylate (aspirin) or salicylate-containing products within the past month
• Participant born at less than 37 weeks gestation and is currently less than 1 year of age

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ruth A. Karron, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Center for Immunization Research, JHU

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29509911 (View on PubMed)

Other Identifiers

CIR 291

Identifier Type: -

Identifier Source: org_study_id