Safety Study of a Human Metapneumovirus Challenge Virus in Healthy Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01109329
First received: April 21, 2010
Last updated: December 31, 2012
Last verified: December 2012
  Purpose

Human metapneumovirus (HMPV) is a virus that can cause respiratory illness. In older adults, those with asthma, infants, and children, illness can be severe, but in healthy adults the virus frequently causes no symptoms. The National Institute of Allergy and Infectious Diseases (NIAID) is working to develop a vaccine for HMPV that could be given to infants. Before potential vaccines can be tested, information about how HMPV affects healthy adults is needed. This study will examine the effects of exposure to HMPV in healthy adults.


Condition Intervention Phase
Human Metapneumovirus
Biological: HMPV challenge virus
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase 1 Inpatient Study of rHMPV-SHs, a Human Metapneumovirus Challenge Strain, Administered to Healthy Adults in Isolation

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of challenge virus (rHMPV-SHs) infection, defined as virus shedding in respiratory secretions or serological evidence of HMPV infection [ Time Frame: Measured at baseline and on Days 1 to 9 ] [ Designated as safety issue: No ]
  • rHMPV-SHs shedding, as measured by peak virus titer, mean sum of daily virus titers, and total duration of shedding [ Time Frame: Measured at baseline and on Days 1 to 9 ] [ Designated as safety issue: No ]
  • Frequency and severity of respiratory illness [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Magnitude, frequency, and duration of serum and nasal wash antibody responses induced by rHMPV-SHs [ Time Frame: Measured at baseline and on Days 28, 120, and 180 ] [ Designated as safety issue: No ]
  • Correlation between virus shedding and severity of clinical illness [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • Cytokine and chemokine concentrations in nasal wash samples and relationships between cytokine/chemokine induction, viral replication, and illness [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
  • T-cell mediated and innate immune responses [ Time Frame: Measured at baseline and on Days 8, 28, and 180 ] [ Designated as safety issue: No ]
  • Whether HMPV infection induces characteristic gene expression patterns in cells obtained from blood or nasal wash [ Time Frame: Measured at baseline and Days 3, 5, 7, 8, 28, and 180 ] [ Designated as safety issue: No ]
  • Relationship between the development of immune responses and clearance of rHMPV-SHs [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: June 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HMPV challenge virus
Participants will receive the HMPV challenge virus.
Biological: HMPV challenge virus
Single dose of 10^6 plaque forming units (PFU) of recombinant HMPV small hydrophobic genes (rHMPV-SHs)

Detailed Description:

Human metapneumovirus (HMPV), a virus that causes respiratory illness, was first discovered in 2001, although humans have been infected with it for at least 50 years. HMPV may cause upper respiratory illness or no symptoms at all in healthy adults, but older adults, adults with asthma, and children may be at risk of more serious illness. HMPV is a leading cause of viral lower respiratory infection (LRI) in children, so finding a vaccine for this virus could substantially reduce the instances of childhood respiratory illnesses.

The National Institute of Allergy and Infectious Diseases (NIAID) is developing a vaccine for HMPV for use in infants, but before starting clinical trials with potential HMPV vaccines, researchers need to study how wild HMPV affects healthy adults. This study will expose healthy adults to a dose of the HMPV virus to assess its ability to infect, cause disease, and create an immune system response.

Participation in this study will last approximately 6 months. Participants will be admitted to an inpatient unit, where they will stay for 10 full days. On their second day in the unit, participants will receive a single dose of the virus, delivered via nose drops. Twice each day while participants are inpatients, they will undergo physical exams and have their vital signs recorded. Nasal washes and blood samples will be collected before participants receive the virus, and then daily nasal washes will be collected until they are discharged from the inpatient unit. Participants will be discharged from the unit on the 9th day after receiving virus if their nasal wash from Day 8 was free of virus. Follow-up visits will occur 28, 120, and 180 days after participants receive the virus. During follow-up visits nasal washes and blood samples will be collected.

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator
  • Available for the duration of the trial
  • Female subjects must agree to use effective birth control methods for the duration of the study

Exclusion Criteria:

  • Pregnant
  • Currently breastfeeding
  • Evidence of clinically significant diseases in the nervous system, heart, lungs, liver, autoimmune system, or kidney or involving rheumatism, as determined by medical history, physical examination, or laboratory studies, including urine testing.
  • Clinically significant alanine aminotransferase (ALT) levels, as determined by the principal investigator (PI)
  • Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, affects the ability to understand and cooperate with the study protocol
  • Human metapneumovirus (HMPV) specific serum immunoglobulin A (IgA) titer greater than 1:50
  • HMPV-specific nasal wash IgA titer greater than 1:50
  • Positive urine drug toxicology test indicating narcotic use
  • Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months
  • Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol
  • History of hypersensitivity reactions
  • Diagnosis of asthma or reactive airway disease within the past 2 years
  • Positive result on test for HIV
  • Positive result on test for hepatitis C virus (HCV)
  • Positive result on test for hepatitis B virus surface antigen (HBsAg)
  • Known immunodeficiency syndrome
  • Use of corticosteroids (excluding topical or nasal preparations) or immunosuppressive drugs within 30 days prior to inoculation
  • Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to inoculation with challenge virus, rHMPV-SHs
  • History of a surgical removal of the spleen
  • Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study inoculation
  • Current smoker unwilling to stop smoking for the duration of the study
  • Receipt of another investigational vaccine or drug within 30 days prior to study inoculation
  • Body mass index (BMI) greater than 35
  • Shares household with a child younger than 60 months of age or an immunocompromised individual
  • Unwillingness to have nasal wash or blood samples saved for future respiratory virus research
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01109329

Locations
United States, Maryland
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Investigators
Principal Investigator: Ruth Karron, MD Johns Hopkins University, Bloomberg School of Public Health
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01109329     History of Changes
Other Study ID Numbers: CIR 270
Study First Received: April 21, 2010
Last Updated: December 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccine

ClinicalTrials.gov processed this record on July 22, 2014