A Phase I Randomized, Double-Blind Trial of the Safety and Immunogenicity of FluMist® A Live, Intranasal Influenza Virus Vaccine vs. Placebo in Immunocompromised Children Ages 5 Through 17 Years of Age
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 10
- 主要终点
- Number of Participants Who Had Reactogenicity Events (REs)
研究概览
简要总结
The main purpose of this study is to get information about the safety of a flu vaccine spray, called FluMist, in children with cancer. The study is also being done to find out how much and how long the vaccine spray can be found in the nose.
详细描述
This study is a randomized, double-blind Phase 1 study of FluMist vs. placebo in mild to moderately immunocompromised children 5 to 17 years of age with cancer. The primary objective of this study is to describe the safety of FluMist compared with placebo in mild to moderately immunocompromised children with cancer. The secondary objectives of this study are to describe the immune responses following vaccination with FluMist and to determine the incidence and duration of viral replication following vaccination with FluMist.
The standard 0.5 mL dose of vaccine or placebo was administered intranasally. Patients were evaluated at four visits scheduled between days 3-5, days 7-10, days 14-28, and days 35-42 for viral shedding via nasal swabs. Safety outcomes were collected at study clinic visits or by telephone contact through 42 days post dose. Serious adverse events and significant new medical conditions were collected through 180 days after receipt of investigational product.
Immune responses were measured by detection of influenza-specific antibodies as measured by the standard hemagglutination inhibition (HAI) assay. Influenza-specific serum antibody isotype levels were determined and nasal swab specimens were analyzed for the expression of influenza-specific immunoglobulin A (IgA). Serum was analyzed for its ability to neutralize viral particles from infecting Madin-Darby canine kidney cells (microneutralization). Baseline immunosuppression as measured by expression of T- and B-lymphocyte subsets was compared to immunosuppression at time points after vaccination. The duration of viral replication and the titers of live-attenuated influenza virus shed was evaluated from nasal swab specimens collected at scheduled time points after administration of FluMist.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 5 through 17 years of age (not yet reached their 18th birthday) at the time of entry into the study;
- •Patient's parent or legal guardian available by telephone during the course of the study;
- •Written informed consent (assent if applicable) and Health Insurance Portability and Accountability Act (HIPAA) authorization (if applicable) obtained from the patient's parent or legal guardian;
- •Ability of the patient or patient's parent/guardian to comply with the requirements of the protocol;
- •Currently receiving chemotherapy and/or radiation therapy for the treatment of cancer or have received chemotherapy in the past 12 weeks;
- •If the subject's underlying cancer is a solid tumor, current status must be stable disease, partial response, or complete response to therapy; if the subject's underlying disease is a hematologic malignancy, current status must be in remission;
- •Estimated life expectancy of >1 year; and
- •Currently has no worse than mild to moderate immunosuppression (meets none of the exclusion criteria).
排除标准
- •History of hypersensitivity to any component of FluMist, including egg or egg products, or monosodium glutamate;
- •History of hypersensitivity to gentamicin;
- •Close contact with a severely immunocompromised patient (e.g., a hematopoietic stem cell transplant patient, during those periods in which the immunocompromised patient requires care in a protective environment);
- •History of Guillain-Barré syndrome;
- •History of asthma;
- •Use of aspirin or salicylate-containing products in the 30 days prior to study vaccination or expected receipt within the study duration;
- •Use of anti-influenza medications (including amantadine, rimantadine, oseltamivir, and zanamivir) within 14 days prior to enrollment or expected receipt (unless medically indicated) during this study;
- •Currently receiving inhaled steroid therapy;
- •Receipt of immunoglobulin within the past 90 days;
- •Receipt of stem cell transplant;
- •Acute febrile [>100.0°F (37.8°C) oral] illness or acute respiratory illness, e.g., cough or sore throat, within three days prior to enrollment;
- •Administration of any live vaccine within 30 days prior to enrollment or if receipt of another live vaccine is expected within 30 days after the vaccination in this study;
- •Administration of any inactivated vaccine within two weeks prior to enrollment or if receipt of another inactivated vaccine is expected within two weeks after the vaccination in this study;
- •Receipt of an investigational product studied under an investigational new drug (IND) within 10 days prior to study entry or expected receipt of such an investigational product within 10 days after study vaccination (Note: an investigational product not studied under an IND is allowed at the investigator's discretion);
- •Pregnancy or, in biologically capable females (e.g., menses within the last year), not willing to agree to acceptable birth control for three months after study vaccination (for those biologically capable, a urine pregnancy test must be performed on the day of vaccination with a negative result);
- •Female who is breastfeeding or lactating;
- •Any condition or receipt of other medication that, in the opinion of the investigator, might interfere with the evaluation of the vaccine or interpretation of study results;
- •At the study screening visit (within 16 days before study vaccination) a CD4+ T cell percentage of <15%;
- •At study entry, an absolute neutrophil count less than or equal to 500 cells/mm3;
- •Receipt of high-dose systemic corticosteroids (≥ 2 mg/kg total of prednisone or equivalent given daily or on alternating days) for ≥ 14 consecutive days within 30 days prior to or following study vaccination
结局指标
主要结局
Number of Participants Who Had Reactogenicity Events (REs)
时间窗: 0-42 days after study vaccination
Reactogenicity events (REs) are predefined solicited adverse events (AEs) that can potentially occur after vaccine administration. The REs for this study included fever, runny nose/nasal congestion, sore throat, cough, vomiting, headache, muscle aches, chills, tiredness, and irritability.
Number of Participants Who Had Adverse Events (AEs)
时间窗: 0-42 days after study vaccination
An AE is any untoward medical occurrence in a patient or clinical investigations study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Number of Significant New Medical Conditions (SNMCs)
时间窗: 43-180 days after study vaccination
A significant new medical condition is defined as a new diagnosis of a chronic medical condition that does not meet the criteria of a SAE.
Number of Participants Who Had Serious Adverse Events (SAEs)
时间窗: 0-180 days after study vaccination
An SAE is any AE that results in any of the following outcomes: •Death • Life-threatening • Inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant disability or incapacity • Congenital anomaly/birth defect (in the offspring of a study participant) • An important medical event that may may jeopardize the study participant and may require medical or surgical intervention to prevent one of the outcomes listed above.
次要结局
- Number of Participants Shedding Vaccine-like Virus(Unscheduled visits occurring during 0-42 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - CD19(7-10 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Neutrophils(pre-dosing (Day 0))
- T- and B-lymphocyte Subsets by Flow Cytometry - CD3(7-10 days after study vaccination)
- Influenza A/H3N2 IgG(35-42 days after study vaccination)
- INF-Gamma(35-42 days after study vaccination)
- Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza A/H3N2 HAI Titers From Baseline to Day 35-42(Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination)
- Number of Participants Who Experienced a >= 4-fold Rise in Influenza A/H1N1 Microneutralization Titers From Baseline to Day 35-42(Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination)
- Influenza A/H1N1 Immunoglobulin G (IgG)(pre-dosing (Day 0))
- Influenza A/H1N1 Immunoglobulin M (IgM)(pre-dosing (Day 0))
- T- and B-lymphocyte Subsets by Flow Cytometry - CD4(7-10 days after study vaccination)
- Interferon (INF)-Gamma(pre-dosing (Day 0))
- Interleukin (IL)-4(pre-dosing (Day 0))
- Number of Participants Who Experienced a >= 4-fold Rise in Influenza B Microneutralization Titers From Baseline to Day 35-42(Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination)
- Influenza B IgA(35-42 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - Cluster of Differentiation (CD) 19(pre-dosing (Day 0))
- Human Leukocyte Antigen (HLA) Matched Tetramers CD8+(pre-dosing (Day 0))
- Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza A/H1N1 Hemagglutination Inhibition (HAI) Titers From Baseline to Day 35-42(Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination)
- Number of Participants Who Experienced a >= 4-fold Rise in Serum Influenza B HAI Titers From Baseline to Day 35-42(Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination)
- Influenza A/H1N1 Immunoglobulin A (IgA)(pre-dosing (Day 0))
- Influenza A/H1N1 IgA(35-42 days after study vaccination)
- Influenza A/H1N1 IgG(35-42 days after study vaccination)
- Influenza A/H1N1 IgM(35-42 days after study vaccination)
- Influenza A/H3N2 IgM(35-42 days after study vaccination)
- Influenza B IgM(35-42 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - CD8(7-10 days after study vaccination)
- IL-4(35-42 days after study vaccination)
- HLA Matched Tetramers CD8+(35-42 days after study vaccination)
- Number of Participants Who Experienced a >= 4-fold Rise in Influenza A/H3N2 Microneutralization Titers From Baseline to Day 35-42(Baseline (pre-dosing on Day 0) and 35-42 days after study vaccination)
- Influenza A/H3N2 IgA(35-42 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - White Blood Cells(7-10 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - Absolute Lymphocytes(7-10 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - CD56(7-10 days after study vaccination)
- T- and B-lymphocyte Subsets by Flow Cytometry - Lymphocytes(7-10 days after study vaccination)
- Influenza B IgG(35-42 days after study vaccination)