Metapneumovirus Clinical Trial
Official title:
A Phase I Study of the Safety and Immunogenicity of the Recombinant Live-Attenuated Human Metapneumovirus Vaccine, rHMPV-Pa Lot HMPV #101A, Delivered as Nose Drops to Adults 18 to 49 Years of Age, HMPV-Seropositive Children 12 to 59 Months of Age, and HMPV-Seronegative Infants and Children 6 to 59 Months of Age
People who are infected with human metapneumovirus (HMPV) may develop upper and lower respiratory illnesses. Children are particularly sensitive to HMPV infection. This study will evaluate the safety and immune response of an HMPV vaccine in healthy adults, HMPV-seropositive children, and HMPV-seronegative infants and children.
| Status | Completed |
| Enrollment | 60 |
| Est. completion date | January 2015 |
| Est. primary completion date | October 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 6 Months to 49 Years |
| Eligibility |
Inclusion Criteria for Adults: - Adult males and non-pregnant, non-nursing females 18 to 49 years old - In good health without significant medical illness, physical examination findings, or significant laboratory abnormalities in urinalysis, complete blood count (CBC), alanine aminotransferase (ALT), or creatinine as determined by the investigator - Available for the duration of the study - Willing to participate in the study as evidenced by signing the informed consent document - Female participants of childbearing potential must have negative urine pregnancy tests and must agree to use effective birth control methods (e.g., birth control pills, diaphragm and foam, condoms with spermicide, Depo-Provera) until 28 days after vaccination Exclusion Criteria for Adults: - Pregnant, as determined by a positive urine beta-human chorionic gonadotropin (HCG) test - Breastfeeding - Females of childbearing potential who are unwilling to practice effective birth control as described in the inclusion criteria - Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis - Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the participant to understand and cooperate with the study protocol - Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a participant in the study or would render the participant unable to comply with the protocol - Has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the 12 months before study entry - History of a severe allergic reaction or anaphylaxis - History of splenectomy - Current diagnosis of asthma in the 2 years prior to study entry - Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blot tests for HIV-1 - Positive ELISA and confirmatory immunoblot tests for hepatitis C (HCV) - Positive ELISA HBsAg - Abnormal urinalysis/urine dip - Known immunodeficiency syndrome - Current use of nasal or systemic steroid medications - Receipt of blood products (including immunoglobulin) in the 3 months before study entry - Current smoker unwilling to stop smoking for the duration of the study. More information on this criterion can be found in the protocol. - Receipt of another investigational vaccine or investigational drug within 28 days of receiving this investigational HMPV vaccine - Receipt of a live vaccine in the 4 weeks before study entry, a killed vaccine in the 2 weeks before study entry, or immune globulin within the 3 months prior to receiving the investigational vaccine - Previous enrollment in an HMPV vaccine or viral challenge study - Known hypersensitivity to any vaccine component - Adults whose professional and/or personal responsibilities involve caring for children less than 59 months of age or for immunosuppressed individuals - Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg - Body mass index (BMI) greater than 35 Inclusion Criteria for Seropositive Children: - Healthy children 12 to 59 months of age, whose parent/guardian understands and signs the informed consent and who agrees to vaccine administration following a detailed explanation of the study - Seropositive for HMPV as defined by serum neutralizing antibody titer greater than or equal to 1:40. If a child between 12 and 59 months of age is determined to be HMPV seropositive prior to Day 56, s/he does not need an additional screening serum specimen, but a prevaccination serum specimen must be obtained. - Participant's history has been reviewed and they have undergone a physical examination indicating that s/he is in good health - Available for the duration of the study Exclusion Criteria for Seropositive Children: - Known or suspected impairment of immunological functions, including maternal history of positive HIV test, receiving immunosuppressive therapy including systemic corticosteroids, or bone marrow/solid organ transplant recipients (topical steroids, topical antibiotics, and topical antifungal medications are acceptable) - Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders - Previous immunization with an HMPV vaccine - Current use of nasal or systemic steroid medications - Previous serious vaccine-associated adverse event or anaphylactic reaction - Known hypersensitivity to any vaccine component - Lung or heart disease, including any wheezing event or reactive airway disease. People with clinically insignificant cardiac abnormalities requiring no treatment may be enrolled. People who wheezed once or received bronchodilator therapy once in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months before study entry may also be enrolled. - Member of a household that includes an immunocompromised individual or infants less than 12 months of age, other than a study participant - Attends day care with infants less than 12 months of age, or immunosuppressed individuals, and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization. Children who attend facilities that separate children by age and minimize opportunities for transmission of virus through direct physical or aerosol contact are acceptable. - Receipt of another investigational vaccine or investigational drug within 28 days of receiving this investigational HMPV vaccine Inclusion Criteria for Seronegative Infants and Children: - Healthy children 6 to 59 months of age whose parents/guardians can understand and sign the informed consent and who agree to vaccine administration following detailed explanation of the study - Seronegative for HMPV antibody as defined by serum neutralizing antibody titer less than 1:40 as determined within 42 days prior to inoculation - Participant's history has been reviewed and they have undergone a physical examination indicating that s/he is in good health - Available for the duration of the study Exclusion Criteria for Seronegative Infants and Children: - Known or suspected impairment of immunological functions, including maternal history of positive HIV test, receiving immunosuppressive therapy including systemic corticosteroids, or bone marrow/solid organ transplant recipients (topical steroids, topical antibiotics, and topical antifungal medications are acceptable) - Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders - Previous immunization with an HMPV vaccine - Current use of nasal or systemic steroid medications - Previous serious vaccine-associated adverse event or anaphylactic reaction - Known hypersensitivity to any vaccine component - Lung or heart disease, including any wheezing event or reactive airway disease. People with clinically insignificant cardiac abnormalities requiring no treatment may be enrolled. People who wheezed once or received bronchodilator therapy once in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months before study entry may also be enrolled. - Member of a household that includes an immunocompromised individual or infants less than 12 months of age, other than a study participant - Attends day care with infants less than 12 months of age and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization. Children who attend facilities that separate children by age and minimize opportunities for transmission of virus through direct physical or aerosol contact are acceptable. - Receipt of another investigational vaccine or investigational drug within 28 days of receiving this investigational HMPV vaccine Temporary Exclusion Criteria for All Age Groups: The following are temporary or self-limiting conditions, and once resolved, the person may be enrolled, if otherwise eligible. If the period of temporary exclusion is more than 56 days for adults or HMPV-seropositive children, or more than 42 days for HMPV-seronegative children, participants will need to be rescreened. - Fever (adult oral temperature of greater than or equal to 100.4°F [38°C], or pediatric rectal temperature of greater than or equal to 100.4°F [38.0°C]), acute upper respiratory illness (including nasal congestion significant enough to interfere with successful vaccination), or acute otitis media - Received any killed vaccine or live attenuated rotavirus vaccine within the 2 weeks before study entry, any other live vaccine within the 4 weeks before study entry, or gamma globulin (or other antibody products) within the 3 months before study entry - Received antibiotics or systemic or nasal steroid therapy for acute illness within the previous 3 days prior to vaccination (topical steroids and topical antibiotics or antifungal preparations are permitted) - Infant or child participant has received salicylate (aspirin) or salicylate-containing products within the 1 month before study entry - Children born at less than 37 weeks gestation will be deferred from participation until they are at least 1 year of age |
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| United States | Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health | Baltimore | Maryland |
| United States | Seattle Children's Hospital | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Herfst S, Fouchier RA. Vaccination approaches to combat human metapneumovirus lower respiratory tract infections. J Clin Virol. 2008 Jan;41(1):49-52. Epub 2007 Dec 4. Review. — 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
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Frequency of vaccine-related reactogenicity events that occur during the acute monitoring phase of the study | Measured at Days 0-12 for adult and seropositive participants, Days 0-28 for seronegative participants | Yes | |
| Primary | Proportion of participants that develop 4-fold or greater rises in human metapneumovirus (HMPV) neutralizing antibody titer following vaccination. | Measured following the vaccination | No | |
| Secondary | The number of vaccinated children and infants infected with rHMPV-Pa | Measured at study completion | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Withdrawn |
NCT03502694 -
Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Oral Lumicitabine Regimens in Hospitalized Adult Participants Infected With Human Metapneumovirus
|
Phase 2 |