Evaluating the Infectivity, Safety, and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine in RSV-Seronegative Infants and Children 6 to 24 Months of Age

NCT02952339 | Completed Phase 1 DMC

• 1 other identifier: CIR 311
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

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 6 to 24 months of age. This study is a companion study to IMPAACT 2011.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (9)

• Grades of study product-related solicited adverse events (AEs) as defined in the protocol

  Measured through Day 28

• Grades of study product-related unsolicited AEs

  Measured through Day 28

• Grades of study product-related serious adverse events (SAEs)

  Measured through Day 56

• Number of participants with infection with vaccine virus

  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) or 2) greater than or equal to 4-fold rise in RSV neutralizing antibody titer from Study Day 0-56

  Measured through Day 56

• Peak titer of vaccine virus shed

  Measured through Day 28

• Duration of vaccine virus shedding in nasal washes measured by culture

  Measured through Day 28

• Duration of vaccine virus shedding in nasal washes measured by RT-PCR

  Measured through Day 28

• Greater than or equal to 4-fold rise in RSV-neutralizing antibody titer

  Measured through Day 56

• Antibody responses to RSV F glycoprotein as assessed by ELISA

  Measured through Day 56

Secondary Outcomes (3)

• 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

  Measured through 5 months

• Measurement of antibody responses in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season

  Measured at the participant's last study visit, up to a total of 6 to 13 months after study entry depending on when participants enroll in the study

• Changes from baseline in the B cell responses to RSV

  Measured through participant's last study visit, up to a total of 6 to 13 months after study entry depending on when participants enroll in the study

Study Arms (2)

RSV LID ΔM2-2 1030s vaccine

EXPERIMENTAL

Participants will receive a single dose of the RSV LID ΔM2-2 1030s vaccine at Day 0.

Biological: RSV LID ΔM2-2 1030s vaccine

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo vaccine at Day 0.

Biological: Placebo

Interventions

RSV LID ΔM2-2 1030s vaccine BIOLOGICAL

10\^5.0 PFU; administered as nose drops

RSV LID ΔM2-2 1030s vaccine

Placebo BIOLOGICAL

Administered as nose drops

Placebo

Eligibility Criteria

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

You may qualify if:

• Greater than or equal to 6 months (greater than or equal to 180 days) of age at the time of screening and less than 25 months (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
• Parents/guardians are willing and able to provide written informed consent
• 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
• 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 Center for Disease Control Advisory Committee on Immunization Practices \[ACIP\])
• Participant is expected to be available for the duration of the study

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 receipt of placebo in this study or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG)
• 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 documented 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 CIR 311, 312 or 313 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 HIV infected
• a person who has received chemotherapy within the 12 months prior to enrollment
• a person receiving immunosuppressant agents

Sponsors & Collaborators

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

Study Sites (2)

Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

Center for Immunization Research South

Laurel, Maryland, 20708, United States

Location

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

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: October 31, 2016
• First Posted: November 2, 2016
• Study Start: August 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: February 13, 2018

Record last verified: 2018-02

Locations

US (2)