Clinical Trial of Safety (Reactogenicity) and Immunogenicity of Needle-free Jet Injection of Reduced-dose, Intradermal Influenza Vaccine (INF) Administered to >= 6 to < 24 Month-old Infants and Toddlers in the Dominican Republic
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Rates of seroconversion (SC) on HI assay 1 month after dose 2. SC defined as titer >= 40 among initial-seronegatives (titer < 8 on day 0); OR, a followup titer which rises >= 4-fold.
研究概览
简要总结
This is a sequential phase I and II, controlled, double-blinded study to determine whether immune responses suggesting protection against influenza can safely be induced in young children by two reduced doses one month apart of 0.1 mL of a trivalent inactivated influenza vaccine (INF) administered by the intradermal (ID) route with an investigational ID spacer on a United States (U.S.)-licensed needle-free jet injector (JI), compared to two standard intramuscular (IM) 0.25 mL doses by needle-syringe (N-S) in this age group. The locale is a developing country where financial restraints for the use of full-dose influenza vaccine would limit protection from an influenza pandemic threat, where N-Ss pose dangers and drawbacks in clinical use, and where Mantoux-type N-S ID injections are difficult to administer during mass campaigns.
详细描述
Randomized, observer-blinded, clinical pilot (phase I) trial of safety, followed by a clinical (phase II) trial of safety and non-inferiority of immune response to the standard route and dose for the merged subjects from both phases.
Phase I - Influenza-vaccine naïve children (n = 48) aged >= 6 to < 24 months will be randomized in a 1:1:1 ratio to the following three study arms, each to receive two doses on days 0 and 28 of trivalent inactivated influenza (INF) vaccine (Vaxigrip®, Sanofi Pasteur, Lyon, France) into the left thigh (< 12 months) or left deltoid (≥ 12 months):
- Group "ID-JI-0.1" (n = 16) - reduced 0.1 mL INF doses administered intradermally (ID) by needle-free jet injector (JI) (Biojector® 2000 subcutaneous syringe no. 2 [green color code], with 2 cm investigational spacer, Bioject Medical Technologies, Inc., Portland, OR, USA)
- Group "IM-NS-0.1" (n = 16) - reduced 0.1 mL INF doses administered intramuscularly (IM) needle-syringe (NS) (via 22-25 gauge needle, minimum 25 mm/1-inch length)
- Group "IM-NS-0.25" (controls) (n = 16) - full 0.25 mL INF doses administered intramuscularly (IM) by needle-syringe (NS) (22-25 gauge needle, minimum 25 mm/1-inch length)
Phase II - Upon assessment of the safety profile from phase I by the unblinded Data Safety Monitoring Board (DSMB), with its approval an additional 402 children will be recruited and randomized (134 per group) as in phase I above. Total subjects in phase I and II = 450 (150 in each of three study arms).
Adverse Event Diaries: Parents will be trained to complete a diary form to observe, measure, and record solicited local reactions for the injection site and systemic signs and symptoms for the child for days 0 through 7 after vaccination, plus unsolicited symptoms, illness, and medications for days 0 through 28.
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
- 6 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age from > = 6 to < 24 months (not having reached 2nd birthday).
- •Born after a full-term (≥ 37 weeks), and birth weight of >= 2.5 kg (>= 5 pounds, 8 ounces)
- •History of prior or first attendance as a patient, or as a sibling of a patient, seeking routine immunization or other clinical care at the Hospital Infantíl Robert Reid Cabral (HIRRC)
- •The parent(s) or legal guardian(s) provide(s) written informed consent and agree(s) to bring the infant back to the clinic for all visits scheduled in the study
- •Up-to-date for routine doses of vaccines officially recommended for the patient's age in the Dominican Republic to prevent tuberculosis, polio, diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae B
- •In good health, as determined by medical history and physical examination collected in accordance with the Case Report Form (CRF), and by the clinical judgment of the investigators.
排除标准
- •Infants WHOSE PARENT(S)/LEGAL GUARDIAN(S):
- •Are unable or unwilling to give written informed consent for their infant to participate in the study
- •Cannot be contacted by telephone (family's own or a neighbor's) if necessary for adverse events if scheduled followup return appointments are missed
- •Are unable to complete the diary for adverse events; are unable to measure and record temperatures or maximal diameter of local reactions or limb circumference; or have difficulty understanding written instructions; or other factors which indicate exclusion in the judgement of the study staff.
- •INFANTS who:
- •Have fever (by parental report or by rectal temperature ≥ 38.5° C or axillary ≥ 38.0° C) currently or within the past 3 days, or who are currently suffering from an acute or chronic infectious disease (including known HIV)
- •Have had an acute or chronic infection requiring systemic antimicrobial therapy (antibiotic or antiviral) or other prescribed treatment within the past 21 days. This includes any underlying illness that may limit their response to vaccination, such as those receiving intravenous immunoglobulin for agammaglobulinemia, or systemic steroid therapy.
- •Are malnourished, defined by weight less than two standard deviations below the median weight for their age
- •Are allergic to eggs, or have a history of any anaphylactic shock, asthma, urticaria, or other allergic reaction after previous vaccinations, or have allergy or hypersensitivity to any component of the study vaccine
- •Have ever previously received any influenza vaccine
- •Have received within the prior 28 days, or for whom there is the indication to receive in the next 56 days, any non-study vaccination or investigational agent outside of the study
- •Have a known bleeding diathesis, or any condition with a prolonged bleeding time
- •Currently have any serious confirmed or suspected disease, such as metabolic, cardiac, or autoimmune disease, or diabetes
- •Have a history of epilepsy or a seizure disorder, or neurodevelopmental disorders such as autism
- •Have a genetic anomaly or known cytogenic disorder (e.g., Down's syndrome)
- •Have leukemia, lymphoma, or any other cancer/neoplasm
- •Have known or suspected immune dysfunction, including HIV infection, or receives(ed) immunosuppressive therapy, including systemic corticosteroids
- •Have ever received blood, blood products, or parenteral preparations of immunoglobulin
- •Have any other serious disease (e.g., with signs of cardiac or renal failure), including progressive neurologic disease
- •Have any condition which, in the opinion of the investigator, may interfere in the evaluation of the objectives of the study
结局指标
主要结局
Rates of seroconversion (SC) on HI assay 1 month after dose 2. SC defined as titer >= 40 among initial-seronegatives (titer < 8 on day 0); OR, a followup titer which rises >= 4-fold.
时间窗: One month after each of doses 1 and 2.
seroconversion and safety assessed through occurrence of local and systemic reactions
次要结局
- Geometric mean titers (GMT) on HI(One month after each of doses 1 and 2.)
- Rates of local and systemic reactions(Up to 42 days for prompted symptoms after investigational doses 1 and 2. Up to 6 months for unsolicited ones.)
- Seroprotection (SP) on HI assay, defined as >= 40 regardless of baseline(One month after each of doses 1 and 2.)
- Geometric mean increase (GMI) on HI(One month after each of doses 1 and 2.)
研究者
Pedro Moro
epidemiologist
Centers for Disease Control and Prevention