Trial to Investigate Immune Responses Elicited by a Liquid Formulation of Influenza Virus Vaccine (CAIV-T) in Healthy Children

Study Overview
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Brief Summary
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To perform a variety of assays on blood, nasal washes, and cells obtained from healthy children for the purposes of further investigation of immune responses generated by influenza virus vaccine, trivalent, types A and B, live, cold-adapted (liquid CAIV-T; Wyeth Lederle Vaccines, Marietta, PA). • To assess nasal swab specimens to detect vaccine virus shedding.

Detailed Description
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This was a phase II, prospective, randomized, partially-blinded, placebo-controlled, outpatient study conducted at multiple sites throughout the US in healthy children aged 6 months to less than 36 months. Parents/guardians of subjects were asked to read and sign the informed consent before any study-related procedures were performed. Subjects at each study site were sequentially assigned to 1 of 2 separate blood sample groups referred to as cellular immunity or antibody secreting cell. Subjects within each blood sample group were then randomized 1:1:1:1 to receive a single intranasal dose of CAIV-T 10^7 FFU per dose, CAIV-T 10^5 FFU per dose, placebo or a commercially-available injectable trivalent influenza vaccine (TIV).

Official Title
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A Randomized, Partially-Blinded, Placebo-Controlled Trial to Investigate Immune Responses Elicited by a Liquid Formulation of Influenza Virus Vaccine, Trivalent,Types A & B, Live Cold Adapted (CAIV-T) in Healthy Children Aged 6 to Less Than 36 Months

Conditions
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Influenza

Intervention / Treatment
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* Biological: CAIV-T 10^7
* Biological: CAIVT 10^5
* Biological: Placebo
* Biological: TIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: children at least 6 months of age and less than 36 months of age at the time of enrollment, and in good health as determined by medical history, physical examination and clinical judgement; whose parent/legal guardian has provided written informed consent after the nature of the study has been explained; who, along with their parent or guardian, will be available for the one month duration of the trial (from enrollment to study completion); Exclusion Criteria: whose parents or guardians are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period; with any serious chronic disease (e.g., with signs of cardiac or renal failure or severe malnutrition), including progressive neurological disease; with Down's syndrome or other known cytogenetic disorders; with a known or suspected disease of the immune system or those receiving immunosuppressive therapy, including systemic corticosteroids, or cytotoxic agents (see Section 4.2.2); have an immunosuppressed or an immunocompromised individual living in the same household; with a documented history of hypersensitivity to egg or egg protein or any other component of the study vaccine, placebo or TIV; who, at anytime prior to study enrollment, receives any influenza vaccine (commercial or investigational); with any medical conditions that in the opinion of the investigator might interfere with interpretation of the study results. Note: A pregnant household member is not considered a contraindication to enrollment.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAIV-T 10^5<br>a single intranasal 0.2 mL dose of liquid CAIV-T 10^5 (approximately 0.1 mL into each nostril) | Biological: CAIVT 10^5<br>* a single intranasal 0.2 mL dose of CAIV-T <10^5<br>|
| Experimental: CAIVT 10^7<br>A single intranasal 0.2 mL dose of liquid CAIV-T 10^7 (approximately 0.1 mL into each nostril) | Biological: CAIV-T 10^7<br>* a single intranasal 0.2 mL dose of liquid CAIV-T 107 (approximately 0.1 mL into each nostril)<br>|
| Placebo Comparator: Placebo<br>A single intranasal 0.2 mL dose of placebo | Biological: Placebo<br>* a single intranasal 0.2 mL dose of placebo<br>|
| Active Comparator: Trivalent inactivated vaccine (TIV)<br>A single intramuscular injection of commercially available vaccine | Biological: TIV<br>* commercially available TIV injected intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of influenza-specific immune response following receipt of CAIV-T. | The immune responses were evaluated by hemagglutination inhibition assay (HAI) on serum samples. | Day 0 and Day 27 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine virus shedding | The number of subjects who shed influenza virus vaccine subtypes following vaccination. | Days 2, 6, and 13 | 
| Measurement of influenza-specific immune response following receipt of CAIVT. | The immune responses were evaluated by mucosal IgA ELISA on nasal wash samples. | Day 0 and Day 27 | 
| Measurement of influenza-specific immune responses following receipt of CAIVT | The immune responses were evaluated by assays of cellular immunity (IFN-gamma ELISPOT) and assays that measured the number of antibody secreting cells (B-cell ELISPOT). | Day 0, Day 6, and Day 13 | 
| Assess the safety and tolerability of CAIV-T vaccine in healthy children. | Adverse events and serious adverse events were collect from Day 0 till the end of the study Day 27. | Day 0-27 |