Safety and Immunogenicity of the RSV D46cpΔM2-2 Vaccine in RSV-Seropositive Children and RSV-Seronegative Infants and Children

A Phase I Study of the Safety and Immunogenicity of a Single Dose of the Live Recombinant RSV D46cpΔM2-2 Vero Grown Virus Vaccine (Lot RSV #008A), Delivered as Nose Drops to RSV-Seropositive Children 12 to 59 Months of Age and RSV-Seronegative Infants and Children 6 to 24 Months of Age

The purpose of this study is to evaluate the safety and immunogenicity of the RSV D46cpΔM2-2 vaccine in RSV-seropositive children and RSV-seronegative infants and children.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Biological: Placebo; Biological: D46cpΔM2-2 vaccine

Detailed Description

Human RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age worldwide. This study will evaluate the safety and immunogenicity of the RSV D46cpΔM2-2 vaccine in RSV-seropositive children and RSV-seronegative infants and children. The vaccine will be evaluated in a stepwise fashion beginning in RSV-seropositive children (Group 1), and then in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of D46cpΔM2-2 vaccine or placebo at study entry (day 0).

Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 (RSV-seropositive children) will attend several study visits and will be followed for 28 days. Group 2 (RSV-seronegative infants and children) 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 in Group 2 will also attend several study visits during the time they are enrolled in the study. Study visits for all participants may include clinical assessments, blood collection, and nasal washes.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Bloomberg School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

RSV-Seropositive Children:

Inclusion Criteria:

• Greater than or equal to 12 months of age and less than 60 months of age
• Received routine immunizations appropriate for age
• Serum RSV neutralizing antibody titer greater than or equal to 1:40
• Serum RSV neutralizing antibody result obtained this calendar year
• Pre-inoculation serum RSV neutralizing antibody specimen obtained less than or equal to 56 days prior to inoculation
• Parent/guardian has completed the study comprehension assessment
• Parent/guardian has signed the study informed consent document (ICD)
• Subject is expected to be available for the duration of the study

Exclusion Criteria:

• Evidence of chronic disease
• Within the past 6 months had a decline in height or weight growth that crosses two major growth percentiles (e.g., from above the 75th to below the 25th)
• Known or suspected impairment of immune function
• Maternal history of positive HIV test
• Bone marrow/solid organ transplant recipient
• Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
• Current or unresolved suspected or documented developmental disorder, delay, or other developmental problem
• Cardiac abnormality requiring treatment
• Lung disease or reactive airway disease
• More than one episode of wheezing in the first year of life
• Wheezing episode or received bronchodilator therapy within the past 12 months
• Previous immunization with an experimental RSV vaccine
• Previous receipt or planned administration of anti-RSV antibody product
• Previous serious vaccine-associated AE or anaphylactic reaction
• Known hypersensitivity to any vaccine component
• Previous receipt of immunoglobulin or any antibody products
• Previous receipt of any other blood products within the past 6 months
• Member of a household that contains an infant who is less than 12 months of age during study days 0 to 10
• Member of a household that includes an immunocompromised individual
• Member of a household that includes a person who has received chemotherapy within the past 12 months
• Will attend a daycare facility that does not separate children by age and contains an infant who is greater than 12 months of age during study days 0 to 10

RSV-Seronegative Infants and Children:

Inclusion Criteria:

• Greater than or equal to 6 months of age and less than 25 months of age
• Received routine immunizations appropriate for age
• Serum RSV neutralizing antibody titer is less than 1:40
• Screening and pre-inoculation serum RSV neutralizing antibody specimen obtained less than or equal to 42 days prior to inoculation
• Parent/guardian has completed the study comprehension assessment
• Parent/guardian has signed the study ICD
• Subject is expected to be available for the duration of the study
• Born at greater than or equal to 37 weeks gestation or is currently greater than 1 year of age

Exclusion Criteria:

• Evidence of chronic disease
• Within the past 6 months had a decline in height or weight growth that crosses two major growth percentiles (e.g., from above the 75th to below the 25th)
• Known or suspected impairment of immune function
• Maternal history of positive HIV test
• Bone marrow/solid organ transplant recipient
• Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
• Current or unresolved suspected or documented developmental disorder, delay, or other developmental problem
• Cardiac abnormality requiring treatment
• Lung disease or reactive airway disease
• More than one episode of wheezing in the first year of life
• Wheezing episode or received bronchodilator therapy within the past 12 months
• Previous immunization with an experimental RSV vaccine
• Previous receipt or planned administration of anti-RSV antibody product
• Previous receipt of immunoglobulin or any antibody products
• Previous receipt of any other blood products within the past 6 months
• Previous serious vaccine-associated AE or anaphylactic reaction
• Known hypersensitivity to any vaccine component
• Member of a household which contains an infant who is less than 6 months of age during study days 0 to 28
• Member of a household that includes an immunocompromised individual
• Member of a household that includes a person who has received chemotherapy within the past 12 months
• Will attend a daycare facility that does not separate children by age and contains an infant who is less than 6 months of age during study days 0 to 28

Temporary Exclusion Criteria for RSV-Seropositive and RSV-Seronegative Children:

To be eligible to participate, RSV-seropositive and RSV-seronegative infants and children must satisfy none of the temporary exclusion criteria. The following conditions are temporary or self-limiting. Once the condition is resolved and the subject is otherwise eligible, the subject may be enrolled or rescreened, if necessary.

• Any of the following events at the time of inoculation:

  • fever (rectal temperature of greater than or equal to 100.4°F),
  • upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis)
  • nasal congestion significant enough to interfere with successful inoculation
  • otitis media
• Receipt of any killed vaccine or live-attenuated rotavirus vaccine less than 14 days prior to inoculation

• Receipt of the following medications less than 28 days prior to inoculation:

  • any live vaccine other than rotavirus
  • another investigational vaccine or investigational drug,
  • systemic corticosteroids administered for greater than 14 days at a dosage equivalent to prednisone at greater than 2 mg/kg or 20 mg daily
  • salicylate (aspirin) or salicylate-containing products

• Receipt of a non-permitted concomitant medication or any of the following medications less than 3 days prior to inoculation:

  • systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis,
  • intranasal medications

• Scheduled administration of the following in relation to planned inoculation:

  • killed vaccine within the 14 days following,
  • any live vaccine other than rotavirus within the 28 days following,
  • another investigational vaccine or drug within the 28 days following for RSV-seropositive children and the 56 days following for RSV-seronegative infants and children

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: D46cpΔM2-2 Vaccine; RSV-seropositive children will receive a single dose of 10^6 PFU D46cpΔM2-2 vaccine at study entry (day 0).	Biological: D46cpΔM2-2 vaccine; Delivered as nose drops
Placebo Comparator: Group 1: Placebo; RSV-seropositive children will receive a single dose of placebo at study entry (day 0).	Biological: Placebo; Delivered as nose drops
Experimental: Group 2: D46cpΔM2-2 Vaccine; RSV-seronegative infants and children will receive a single dose of 10^5 PFU D46cpΔM2-2 vaccine at study entry (day 0).	Biological: D46cpΔM2-2 vaccine; Delivered as nose drops
Placebo Comparator: Group 2: Placebo; RSV-seronegative infants and children will receive a single dose of placebo at study entry (day 0).	Biological: Placebo; Delivered as nose drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study	Measured at days 0-10 for seropositive and days 0-28 for seronegative
Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study	Measured at days 0-10 for seropositive and days 0-28 for seronegative
Frequency of vaccine-related lower respiratory illness	Measured during study days 0-28 for seropositive subjects and study days 0-56 for seronegative subjects
Proportion of subjects shedding vaccine virus	Measured during study days 0-28 for seropositive subjects and study days 0-56 for seronegative subjects
Proportion of subjects that develop 4-fold or greater increases in RSV neutralizing antibody titer following vaccination	Measured during study days 0-28 for seropositive subjects and study days 0-56 for seronegative subjects

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Ruth A. Karron, MD, Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): April 26, 2018
• Study Completion (Actual): April 26, 2018

Study Registration Dates

• First Submitted: November 9, 2015
• First Submitted That Met QC Criteria: November 9, 2015
• First Posted (Estimate): November 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: CIR 308