Testing two vaccines for respiratory viruses in young children

Phase I Study of the Infectivity, Safety and Immunogenicity of Two Recombinant, Live-Attenuated, Bovine/Human, Parainfluenza Virus Type 3 (B/HPIV3) Vectored Vaccines Expressing the Fusion Glycoprotein of Human Metapneumovirus (HMPV), Delivered by Nasal Spray to HPIV3-Seropositive Children 24 to <60 Months of Age

This study is testing two new vaccines for respiratory viruses in young children to see if they are safe and effective.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 24 Months to 59 Months
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Drugs / interventions: nirsevimab, chemotherapy
• Locations: 4 sites (Baltimore, Maryland and 3 other locations)
• Trial ID: NCT06546423 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and immunogenicity of two experimental vaccines targeting Human Metapneumovirus (HMPV) and Human Parainfluenza Virus Type 3 (HPIV3) in children aged 24 to 59 months who are seropositive for HPIV3. Participants will receive either one of the two vaccines or a placebo via nasal spray, with a focus on monitoring their health and any adverse effects for 180 days. The study employs a randomized, blinded, and placebo-controlled design, ensuring that neither the participants nor the researchers know which treatment is being administered. Daily contact with participants will occur during the first 28 days to assess safety and health outcomes.

Who should consider this trial

Good fit: Ideal candidates are children aged 24 to 59 months who are seropositive for HPIV3 and in good health.

Not a fit: Patients who are not seropositive for HPIV3 or who have underlying health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to effective vaccines that protect young children from serious respiratory infections caused by HMPV and HPIV3.

How similar studies have performed: Other studies have shown promise in using similar vaccine approaches, but this specific combination is novel.

Eligibility criteria

Inclusion Criteria:

* ≥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

Exclusion Criteria:

* \<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
* Previous receipt or planned administration of human immunoglobulin within the past 6 months. Receipt of licensed monoclonal antibody products for passive prophylaxis against RSV (e.g., nirsevimab) within the past 6 months is not a cause for exclusion
* Previous receipt of any blood products within the past 6 months.
* Previous anaphylactic reaction
* Previous vaccine-associated adverse reaction that was Grade 3 or above.
* Known hypersensitivity to any study product component
* Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
* Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:

  * a person who is HIV-infected
  * a person who has cancer and has received chemotherapy within the 12 months prior to enrollment
  * a person living with a solid organ or bone marrow transplant
* Attends a daycare facility that does not separate children by age and contains a child \<12 months of age at the date of inoculation through the 10th day after inoculation
* Receipt of any of the following prior to enrollment:

  * inactivated influenza vaccine within 3 days prior, or
  * any other inactivated vaccine, messenger RNA (mRNA) vaccine, or live-attenuated rotavirus vaccine within the 14 days prior, or
  * any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
  * another investigational vaccine or investigational drug within 28 days prior, or
  * salicylate (aspirin) or salicylate-containing products within the past 28 days
* Scheduled administration of any of the following after planned inoculation:

  * inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
  * any live vaccine other than rotavirus within the 28 days after, or
  * any salicylate or salicylate-containing products within the 28 days after, or
  * another investigational vaccine or investigational drug in the 56 days after
* Receipt of any of the following medications within 3 days prior to study enrollment:

  * systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
  * intranasal medications, or
  * other prescription medications except the permitted concomitant medications listed below
  * Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents
* Any of the following events at the time of enrollment:

  * fever (temporal or rectal temperature of ≥100.4°F), or
  * upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis), or
  * nasal congestion significant enough to interfere with successful inoculation, or
  * otitis media, or
  * contact with a person diagnosed with COVID-19 disease or active SARS-CoV-2 infection within the preceding 10 days

Where this trial is running

Baltimore, Maryland and 3 other locations

• CIR - Rangos, Johns Hopkins Bloomberg School of Public Health — Baltimore, Maryland, United States (Recruiting)
• CIR South — Columbia, Maryland, United States (Recruiting)
• University of Rochester Medical Center — Rochester, New York, United States (Recruiting)
• Vanderbilt University Medical Center — Nashville, Tennessee, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Ruth Karron, M.D. — Center for Immunization Research, JHBSPH
• Study coordinator: Suzanne Woods, CCRP, CRNP-P

Conditions Human Metapneumovirus; Human Parainfluenza Virus Type 3