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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: CAIVT 10^5; Biological: CAIV-T 10^7; Biological: Placebo; Biological: TIV

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Division of Allergy Immunology and Infectious Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 3 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Robert Walker, MD, MedImmune LLC

Publications and helpful links

General Publications

• Mendelman PM, Rappaport R, Cho I, Block S, Gruber W, August M, Dawson D, Cordova J, Kemble G, Mahmood K, Palladino G, Lee MS, Razmpour A, Stoddard J, Forrest BD. Live attenuated influenza vaccine induces cross-reactive antibody responses in children against an a/Fujian/411/2002-like H3N2 antigenic variant strain. Pediatr Infect Dis J. 2004 Nov;23(11):1053-5. doi: 10.1097/01.inf.0000143643.44463.b1.

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): December 1, 2001
• Study Completion (Actual): December 1, 2001

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): February 17, 2012
• Last Update Submitted That Met QC Criteria: February 15, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: D153-P002