Safety Study of a Human Metapneumovirus Challenge Virus in Healthy Adults

NCT01109329 | Completed Phase 1

• 1 other identifier: CIR 270
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Human Metapneumovirus

Keywords

Vaccine

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Frequency and severity of respiratory illness

  Measured at study completion

Secondary Outcomes (6)

• 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

• Correlation between virus shedding and severity of clinical illness

  Measured at study completion

• Cytokine and chemokine concentrations in nasal wash samples and relationships between cytokine/chemokine induction, viral replication, and illness

  Measured at study completion

• T-cell mediated and innate immune responses

  Measured at baseline and on Days 8, 28, and 180

• 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

Study Arms (1)

HMPV challenge virus

EXPERIMENTAL

Participants will receive the HMPV challenge virus.

Biological: HMPV challenge virus

Interventions

HMPV challenge virus BIOLOGICAL

Single dose of 10\^6 plaque forming units (PFU) of recombinant HMPV small hydrophobic genes (rHMPV-SHs)

HMPV challenge virus

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

Related Publications (4)

• 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.

  PMID: 19845113 BACKGROUND

• 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. doi: 10.1056/NEJMoa025472.

  PMID: 14749452 BACKGROUND

• Talaat KR, Luke CJ, Khurana S, Manischewitz J, King LR, McMahon BA, Karron RA, Lewis KD, Qin J, Follmann DA, Golding H, Neuzil KM, Subbarao K. A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response. J Infect Dis. 2014 Jun 15;209(12):1860-9. doi: 10.1093/infdis/jiu123. Epub 2014 Mar 5.

  PMID: 24604819 DERIVED

• Talaat KR, Karron RA, Thumar B, McMahon BA, Schmidt AC, Collins PL, Buchholz UJ. Experimental infection of adults with recombinant wild-type human metapneumovirus. J Infect Dis. 2013 Nov 15;208(10):1669-78. doi: 10.1093/infdis/jit356. Epub 2013 Aug 1.

  PMID: 23908489 DERIVED

Study Officials

• Ruth Karron, MD

  Johns Hopkins University, Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2010
• First Posted: April 23, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 3, 2013

Record last verified: 2012-12

Locations

US (1)