Safety Study of a Human Metapneumovirus Challenge Virus in Healthy Adults

Human Metapneumovirus Clinical Trial

Official title:

Phase 1 Inpatient Study of rHMPV-SHs, a Human Metapneumovirus Challenge Strain, Administered to Healthy Adults in Isolation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109329
• Other study ID #: CIR 270
• Status: Completed
• Phase: Phase 1
• First received: April 21, 2010
• Last updated: December 31, 2012
• Start date: June 2010
• Est. completion date: December 2010

Study information

• Verified date: December 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Human Metapneumovirus

Intervention

Biological:
• HMPV challenge virus
Single dose of 10^6 plaque forming units (PFU) of recombinant HMPV small hydrophobic genes (rHMPV-SHs)

Locations

Country	Name	City	State
United States	Johns Hopkins Bloomberg School of Public Health	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bruno R, Marsico S, Minini C, Apostoli P, Fiorentini S, Caruso A. Human metapneumovirus infection in a cohort of young asymptomatic subjects. New Microbiol. 2009 Jul;32(3):297-301. — View Citation

Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards KM, Wright PF, Crowe JE Jr. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. 2004 Jan 29;350(5):443-50. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of challenge virus (rHMPV-SHs) infection, defined as virus shedding in respiratory secretions or serological evidence of HMPV infection		Measured at baseline and on Days 1 to 9	No
Primary	rHMPV-SHs shedding, as measured by peak virus titer, mean sum of daily virus titers, and total duration of shedding		Measured at baseline and on Days 1 to 9	No
Primary	Frequency and severity of respiratory illness		Measured at study completion	Yes
Secondary	Magnitude, frequency, and duration of serum and nasal wash antibody responses induced by rHMPV-SHs		Measured at baseline and on Days 28, 120, and 180	No
Secondary	Correlation between virus shedding and severity of clinical illness		Measured at study completion	No
Secondary	Cytokine and chemokine concentrations in nasal wash samples and relationships between cytokine/chemokine induction, viral replication, and illness		Measured at study completion	No
Secondary	T-cell mediated and innate immune responses		Measured at baseline and on Days 8, 28, and 180	No
Secondary	Whether HMPV infection induces characteristic gene expression patterns in cells obtained from blood or nasal wash		Measured at baseline and Days 3, 5, 7, 8, 28, and 180	No
Secondary	Relationship between the development of immune responses and clearance of rHMPV-SHs		Measured at study completion	No