Study of the Infectivity, Safety and Immunogenicity of Two Recombinant, Live-Attenuated, B/HPIV3 Vectored Vaccines Expressing the Fusion Glycoprotein of HMPV Delivered by Nasal Spray to HPIV3-Seropositive Children 24 to <60 Months of Age

NCT06546423 | Completed Phase 1 FDA Drug

• 1 other identifier: CIR363
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

HPIV3 and HMPV are viruses that can cause breathing problems in children. The goal of this clinical trial is to look at the safety of 2 experimental HPIV3/HMPV vaccines in HPIV3-seropositive children ≥ 24 months to \< 60 months of age. Children will receive B/HPIV3/HMPV-PreF-A vaccine, B/HPIV3/HMPV-F-B365 vaccine, or placebo, and participants will not know which study product they have received. The main goals of the study are to find out whether these vaccines are well-tolerated and infectious in HPIV3-seropositive children. The general procedures include daily temperature measurements and daily contact with the participant for the first 28 days, giving a single dose of one of the 2 study vaccines or placebo delivered by nasal sprayer, about 9 in-person visits, a physical examination, 7 clinical assessments, 2 blood samples, 9 nasal swabs and monthly contacts with the participant between Days 29-180. Additional visits may occur if the child has a respiratory illness, fever, or ear infections. The illness visit will include a nasal swab and a clinical assessment.

Conditions

Human Metapneumovirus; Human Parainfluenza Virus Type 3

Outcome Measures

Primary Outcomes (5)

• Number of Grade 1 or higher solicited AEs; any lower respiratory infections

  Day 0 through Day 28

• Percentages of vaccinees with a ≥4-fold rise in HPIV3 neutralizing serum antibody titers

  Day 28

• Percentages of vaccinees with a ≥4-fold rise in HMPV-neutralizing serum antibody titers

  Day 28

• Peak titers of vaccine virus shed

  Study Days 0-28

• Proportion of vaccinees shedding of vaccine virus

  Detected by immunoplaque assay and/or RT-qPCR, and/or ≥4 fold rise in HPIV3 or HMPV-specific serum antibodies, detected by neutralizing antibody assay or ELISA

  Day 28

Secondary Outcomes (1)

• Number of MAAEs and SAEs

  Day 0 through Day 180

Study Arms (3)

B/HPIV3/HMPV-PreF-A vaccine

ACTIVE COMPARATOR

A single dose of intranasal B/HPIV3/HMPV-PreF-A will be administered by a Vax300 VaxINator atomization device.

Biological: B/HPIV3/HMPV-PreF-A vaccine

B/HPIV3/HMPV-F-B365 vaccine

ACTIVE COMPARATOR

A single dose of intranasal B/HPIV3/HMPV-F-B365 will be administered by a Vax300 VaxINator atomization device.

Biological: B/HPIV3/HMPV-F-B365 vaccine

Placebo

PLACEBO COMPARATOR

A single dose of intranasal Lactated Ringer's Solution for Injection will be administered by a Vax300 VaxINator atomization device.

Drug: Placebo

Interventions

B/HPIV3/HMPV-PreF-A vaccine BIOLOGICAL

B/HPIV3/HMPV-PreF-A is a live-attenuated vaccine candidate. The B/HPIV3/HMPV-PreF-A vaccine is provided in a sterile 2.0-mL cryovial, each containing 0.6 mL of vaccine with a titer of approximately 10\^6.7 PFU/mL. The vaccine virus concentrate is diluted with Lactated Ringer's Solution for Injection to a dose of approximately 10\^5.6 PFU in a 0.2 mL volume.

B/HPIV3/HMPV-PreF-A vaccine

B/HPIV3/HMPV-F-B365 vaccine BIOLOGICAL

B/HPIV3/HMPV-F-B365 is a live-attenuated vaccine candidate. The B/HPIV3/HMPV-F-B365 vaccine is provided in a sterile 2.0-mL cryovial, each containing 0.6 mL of vaccine with a titer of approximately 10\^6.3 PFU/mL. The vaccine virus concentrate is diluted with Lactated Ringer's Solution for Injection to a dose of approximately 10\^5.6 PFU in a 0.2 mL volume.

B/HPIV3/HMPV-F-B365 vaccine

Placebo DRUG

Lactated Ringer's Injection, USP is a sterile, nonpyrogenic solution for fluid and electrolyte replenishment. It will be drawn up in a sterile syringe to a volume of 0.2 mL.

Also known as: Lactated Ringer's Solution for Injection

Placebo

Eligibility Criteria

• Age: 24 Months - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• ≥24 months of age and \<60 months of age at the time of inoculation
• HAI Screening for HPIV3-neutralizing antibody is obtained within the calendar year of inoculation
• Seropositive for HPIV3 antibody, defined as serum HPIV3 HAI titer \>1:8
• Pre-inoculation serum sample for HPIV3-neutralizing antibody specimen is obtained no more than 42 days prior to inoculation
• In good health based on review of the medical record, history, and physical examination at the time of inoculation
• Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
• Growing normally for age as demonstrated on a World Health Organization (WHO) growth chart, AND has a current height and weight above the 3rd percentile for age
• Expected to be available for the duration of the study
• Parent/guardian is willing and able to provide written informed consent

You may not qualify if:

• \<24 months of age and \>60 months of age at the time of inoculation.
• Born at less than 34 weeks gestation
• Maternal history of a positive HIV test before or during pregnancy.
• Evidence of chronic disease
• Known or suspected infection or impairment of immunological functions
• Bone marrow/solid organ transplant recipient
• Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
• 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 medically diagnosed wheezing in the first year of life
• Wheezing episode or received bronchodilator therapy or racemic epinephrine within the past 12 months
• Wheezing episode or received bronchodilator therapy after the age of 12 months
• Previous receipt of supplemental oxygen therapy in a home setting
• Previous receipt of an investigational HPIV3 or HMPV vaccine

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Johns Hopkins Bloomberg School of Public Health: collaborator
• Vanderbilt University Medical Center: collaborator
• University of Rochester: collaborator

Study Sites (4)

CIR - Rangos, Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

CIR South

Columbia, Maryland, 21045, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

Ringer's Lactate; Injections

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Ruth Karron, M.D.

  Center for Immunization Research, JHBSPH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To ensure the unbiased clinical evaluation of subjects, all participants' parents/guardians and all staff involved in clinical assessment will remain blinded through completion. To assess the magnitude and duration of vaccine virus replication and ensure continued suitability of these vaccines for this population in this Phase 1 trial, a Scientific Investigator who is not involved in clinical assessment of trial participants, will be unblinded once the final participant in each randomization block has completed the assessment phase on Day 28. Should any concerns arise from this review, these will be shared in a blinded fashion with the Medical Monitor and Sponsor Clinical Safety Office for guidance and assistance. Additionally, this information will be reviewed unblinded by the DSMB in collaboration with the Scientific Investigator and any involved non-study-team consultants before any additional dosing or enrollments proceed.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive B/HPIV3/HMPV-PreF-A vaccine, B/HPIV3/HMPV-F-B365 vaccine or placebo in a 2:2:1 ratio.

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 9, 2024
• Study Start: July 12, 2024
• Primary Completion: June 4, 2025
• Study Completion: June 4, 2025
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: After publication
• Access Criteria: Qualified researchers

Locations

US (4)