Evaluating the Safety and Immune Response to a Respiratory Syncytial Virus (RSV) Vaccine in Adults, RSV-Seropositive Children, and RSV-Seronegative Infants and Children

NCT ID: NCT01459198

Last Updated: 2015-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2015-08-31

Brief Summary

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Human respiratory syncytial virus (RSV) is a common cause of upper respiratory tract illnesses as well as more severe lower respiratory illnesses, including bronchiolitis and pneumonia. RSV affects almost all children within the first 2 years of life. This study will evaluate the safety and immune response to the RSV MEDI ΔM2-2 vaccine among adults, RSV-seropositive children, and RSV-seronegative infants and children.

Detailed Description

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The purpose of this study is to evaluate the safety and immune response of the RSV MEDI ΔM2-2 vaccine in the four groups of participants. The study vaccine will be evaluated in adults, in RSV-seropositive children, and in a dose-ranging study in two groups of RSV-seronegative infants and children.

Conditions

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Respiratory Syncytial Virus Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Seronegative Infants and Children: Placebo Vaccine (Group 4)

Seronegative infants and children will receive one dose of the placebo vaccine intranasally.

Group Type PLACEBO_COMPARATOR

Placebo vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit

Adults: Vaccine (Group 1)

Adult participants will receive one dose of the 10\^6 RSV MEDI ΔM2-2 vaccine intranasally.

Group Type EXPERIMENTAL

RSV MEDI ΔM2-2 vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit, at a dose of 10\^5 or 10\^6 plaque-forming units (PFU), depending on study arm.

Seropositive Children: Vaccine (Group 2)

Seropositive children will receive one dose of the 10\^6 RSV MEDI ΔM2-2 vaccine intranasally.

Group Type EXPERIMENTAL

RSV MEDI ΔM2-2 vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit, at a dose of 10\^5 or 10\^6 plaque-forming units (PFU), depending on study arm.

Seropositive Children: Placebo Vaccine (Group 2)

Seropositive children will receive one dose of the placebo vaccine intranasally.

Group Type PLACEBO_COMPARATOR

Placebo vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit

Seronegative Infants and Children: Vaccine (Group 3)

Seronegative infants and children will receive one dose of the 10\^5 RSV MEDI ΔM2-2 vaccine intranasally.

Group Type EXPERIMENTAL

RSV MEDI ΔM2-2 vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit, at a dose of 10\^5 or 10\^6 plaque-forming units (PFU), depending on study arm.

Seronegative Infants and Children: Placebo Vaccine (Group 3)

Seronegative infants and children will receive one dose of the placebo vaccine intranasally.

Group Type PLACEBO_COMPARATOR

Placebo vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit

Seronegative Infants and Children: Vaccine (Group 4)

Seronegative infants and children will receive one dose of the 10\^6 RSV MEDI ΔM2-2 vaccine intranasally.

Group Type EXPERIMENTAL

RSV MEDI ΔM2-2 vaccine

Intervention Type BIOLOGICAL

Given intranasally once at a baseline study visit, at a dose of 10\^5 or 10\^6 plaque-forming units (PFU), depending on study arm.

Interventions

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RSV MEDI ΔM2-2 vaccine

Given intranasally once at a baseline study visit, at a dose of 10\^5 or 10\^6 plaque-forming units (PFU), depending on study arm.

Intervention Type BIOLOGICAL

Placebo vaccine

Given intranasally once at a baseline study visit

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Adult males and nonpregnant, 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 a study physician, physician assistant, or nurse practitioner
* 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


* Healthy children 12 to 59 months of age, whose parent/guardian understands and signs the study informed consent and agrees to vaccine administration following a detailed explanation of the study
* Seropositive for RSV, defined by serum RSV neutralizing antibody titer greater than 1:40
* Person'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


* Healthy children 6 to 24 months of age whose parents/guardians can understand and sign the informed consent and agree to vaccine administration following detailed explanation of the study
* Seronegative for RSV antibody, defined by serum RSV neutralizing antibody titer less than 1:40 determined within 30 days prior to inoculation
* Person'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

* Pregnant, as determined by a positive urine human chorionic gonadotropin (beta-HCG) test
* Breastfeeding
* Females of childbearing potential who are unwilling to practice effective birth control
* 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 person 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 person 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 prior to study entry
* History of a severe allergic reaction or anaphylaxis
* History of splenectomy
* Current diagnosis of asthma within 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 virus (HCV)
* Positive ELISA hepatitis B surface antigen (HBsAg)
* Abnormal urinalysis/urine dip
* Known immunodeficiency syndrome
* Receipt of blood products (including immunoglobulin) within the 3 months prior to study entry
* Current smoker unwilling to stop smoking for the duration of the study
* Previous enrollment in an RSV vaccine study
* Known hypersensitivity to any vaccine component
* Has professional and/or personal responsibilities that involve caring for children younger 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


* 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 RSV vaccine
* Previous serious vaccine-associated adverse event (AE) 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 had one episode of wheezing or received bronchodilator therapy for a single episode of illness in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months may also be enrolled.
* Member of a household that includes an immunocompromised individual or infants younger than 6 months of age, other than a study participant
* Attends day care with infants younger than 6 months of age, and whose parent/guardian is unable or unwilling to suspend daycare for 14 days following immunization. Note: children who attend facilities that separate children by age and minimize opportunities for transmission of virus through direct physical or aerosol contact are acceptable.


* 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 RSV vaccine
* Previous serious vaccine-associated AE 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 had one episode of wheezing or received bronchodilator therapy for a single episode of illness in the first year of life but who have not had any additional wheezing episodes or bronchodilator therapy for at least 12 months may also be enrolled.
* Member of a household that includes an immunocompromised individual or infants younger than 6 months of age, other than a study participant
* Attends day care with infants less than 6 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.


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 more than 30 days for RSV-seronegative children, the person will need to be rescreened. If the period of temporary exclusion is more than 56 days for RSV-seropositive children, a pre-inoculation serum antibody will need to be collected.

* 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 \[38°C\]), or upper respiratory illness (rhinorrhea, cough, or pharyngitis), or nasal congestion significant enough to interfere with successful vaccination, or otitis media
* Has received any killed vaccine or live attenuated rotavirus vaccine within the 2 weeks prior to study entry, any other live vaccine within the 4 weeks prior to study entry, or gamma globulin (or other antibody products) within the 3 months prior to study entry
* Has received another investigational vaccine or investigational drug within 28 days of receiving this investigational RSV vaccine
* Has received antibiotics or systemic or nasal steroid therapy for acute illness within the 3 days prior to vaccination (steroid skin creams or lotions and topical antibiotics or antifungal preparations are permitted)
* Infant or child participant has received salicylate (aspirin) or salicylate-containing products within the 1 month prior to study entry
* Infants born at less than 37 weeks gestation and less than 1 year of age
Minimum Eligible Age

6 Months

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ruth A. Karron, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Bloomberg School of Public Health

Locations

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John Hopkins Center for Immunization Research

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Simoes EA, Rudan I, Weber MW, Campbell H. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010 May 1;375(9725):1545-55. doi: 10.1016/S0140-6736(10)60206-1.

Reference Type BACKGROUND
PMID: 20399493 (View on PubMed)

Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, Grijalva CG, Zhu Y, Szilagyi P. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009 Feb 5;360(6):588-98. doi: 10.1056/NEJMoa0804877.

Reference Type BACKGROUND
PMID: 19196675 (View on PubMed)

Other Identifiers

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CIR 275

Identifier Type: -

Identifier Source: org_study_id