Trial to Compare the Safety, Tolerability, and Efficacy of Influenza Virus Vaccine, (CAIV-T) With Inactivated, Influenza Vaccine, Trivalent, Types A & B, in Adults Aged 60 Years and Older Against Culture-confirmed Influenza (FluMist)

A Prospective, Randomized, Open-Label, Controlled Trial to Compare the Safety, Tolerability, and Efficacy of Influenza Virus Vaccine, Trivalent, Types A & B, Live Cold-Adapted (CAIV-T) With Inactivated, Influenza Vaccine, Trivalent, Types A & B, in Adults Aged 60 Years and Older

To demonstrate that the efficacy over a defined surveillance period against culture-confirmed influenza-illness caused by community-acquired subtypes antigenically similar to those contained in the vaccine, in adults aged at least 60 years at enrollment, of a single intranasally (IN) -administered dose of a liquid formulation of influenza virus vaccine,(CAIV-T) is non inferior compared with that of a single dose of commercially available influenza vaccine inactivated (TIV) administered intramuscularly (IM) prior to the anticipated commencement of the influenza season.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Cold-adapted influenza vaccine trivalent (CAIV-T); Biological: Trivalent Inactivated Vaccine (TIV)

• Study Type: Interventional
• Enrollment (Actual): 3009
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Amanzimtoti, South Africa
    • Jansen van Rensburg
  • Scottburgh South, South Africa
    • Christiaan Tertius de Villiers
  • Dwazulu Natal
    • Durban North, Dwazulu Natal, South Africa
      • Docnor House
  • Pretoria
    • Hazelwood, Pretoria, South Africa
      • Hazelmed Family Practice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• who are aged at least 60 years or older at the time of enrollment;
• who are determined by medical history, physical examination and clinical judgement to be eligible for this study;
• who have provided written informed consent after the nature of the study has been explained;
• who will be available for duration of the trial (from enrollment to November 30th, 2003);
• who can be reached by study staff for the post-vaccination and weekly surveillance contacts [telephone, clinic or home visit].

Exclusion Criteria:

• who are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;
• who are a resident of a nursing home or long-term care facility or other institution receiving skilled or semi-skilled nursing care (refer to Influenza study specific manual). An ambulatory subject who is a resident of a retirement home or village is eligible for the trial;
• with any signs of renal insufficiency requiring supportive therapy or progressive neurological disease. (Subjects with other stable pre-existing disease, defined as disease not requiring change in therapy or hospitalization within 12 weeks before receipt of study vaccination will be eligible).
• with evidence of dementia or other severe cognitive impairment based on Mini Mental State Examination (MMSE) scores (refer to Influenza study specific manual);
• with a known or suspected disease of the immune system or those receiving immunosuppressive therapy, including systemic corticosteroids; or cytotoxic agents;
• who received any blood products, including immunoglobulin, in the period from six months prior to vaccination through to the conclusion of the study;
• 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 CAIV-T or TIV vaccine;
• who were administered any live virus vaccine within one month prior to vaccination or expected to receive another live virus vaccine within one month of vaccination in this study;
• for whom there is intent to administer any other investigational vaccine or agent from one month prior to enrollment through to the conclusion of the study;
• who received a dose of influenza treatment (commercial or investigational) one month prior to enrollment. The prophylactic use of influenza antivirals is not permitted.
• who receive any influenza vaccine in the 6 months prior to enrollment, or intend to receive a non-study influenza vaccine after enrollment;
• 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: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cold-adapted influenza vaccine trivalent (CAIV-T); A single 0.2 mL dose of 10^7 fluorescent focus units was administered intranasally.	Biological: Cold-adapted influenza vaccine trivalent (CAIV-T); Liquid CAIV-T vaccine for this study consisted of 3 cold-adapted, attenuated, reassortant strains, representing the HA and NA antigens of the A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Victoria/504/2000 influenza strains. The vaccine contained no preservatives and had a pH of 7.2 ± 0.5.; Other Names: FluMist
Active Comparator: Trivalent Inactivated Vaccine (TIV); A single dose was administered by intramuscular injection.	Biological: Trivalent Inactivated Vaccine (TIV); Commercially available TIV, inactivated influenza vaccine (Split Virion) BP (Aventis Pasteur MSD, Lyon, France) was administered IM according to the manufacturer's dosing instructions (one 0.5-mL IM dose for adults).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The first episode of a culture-confirmed influenza-illness, caused by community-acquired subtypes antigenically similar to those contained in the vaccine, which occurs at least 15 days following receipt of a dose of study vaccine.	The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.	Dosing through 30Nov2002

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The first episode of a culture-confirmed influenza-illness, caused by any community-acquired subtype, which occurs at least 15 days following receipt of a dose of study vaccine.	The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.	15 days after dosing through 30Nov2002
The first episode in a study subject of a culture-confirmed influenza illness caused by community-acquired virus of each of the subtypes antigenically similar to those contained in the vaccine	The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.	15 days after dosing through 30Nov2002
The first episode in a study subject of a culture-confirmed influenza illness caused by any community-acquired virus of each of the subtypes.	The criteria for obtaining nasal and throat swabs for viral culture were any one of the following: A feeling of "feverishness", An oral temperature ≥37.2ºC, Sore throat, New or increased cough, Malaise, Myalgia. Swabs for viral cultures were also obtained, if, in the opinion of the investigator, the symptom complex so warranted.	15 days after dosing through 30Nov2002
The first episode of influenza-like illness		15 days after dosing through 30Nov2002
Incidence of clinic visits	A possibility of multiple visits per subject; each visit will be counted once in the analysis.	15 days after dosing through 30Nov2002
Incidence of hospitalization		15 days after dosing through 30Nov2002
Incidence of confirmed pneumonia	Pneumonia means one or more areas of acute interstitial or alveolar infiltrates documented radiographically	15 days after dosing through 30Nov2002
Incidence of death due to influenza-like illness	With or without confirmation by viral culture or PCR analysis	15 days after dosing through 30Nov2002
Incidence of seroconversion	Seroconversion is defined as at least a 4-fold increase in titer from baseline to the sample 35 plus or minus 7 days after vaccination. all subjects were to provide serum samples at 2 time points: at study visit 1 prior to vaccination with CAIV-T or TIV, and 35 days ± 7 days following vaccination (study visit 2).	Day 0-35
Incidence of systemic reactogenicity events	The 12 systemic reactions were fever with 3 grades defined as ≥37.2°C, ≥38.6°C, and ≥40°C based on the temperature reported on the diary card in addition to the 9 events reported on the diary card.	Day 0-10
Incidence of local reactions	The local reactions were pain, redness (2 grades: any and significant), and swelling (also 2 grades).	Days 0-10
Incidence of adverse events		Days 0-10

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer

Publications and helpful links

General Publications

• Forrest BD, Steele AD, Hiemstra L, Rappaport R, Ambrose CS, Gruber WC. A prospective, randomized, open-label trial comparing the safety and efficacy of trivalent live attenuated and inactivated influenza vaccines in adults 60 years of age and older. Vaccine. 2011 May 9;29(20):3633-9. doi: 10.1016/j.vaccine.2011.03.029. Epub 2011 Apr 5.

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): November 1, 2002

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): March 14, 2012
• Last Update Submitted That Met QC Criteria: March 13, 2012
• Last Verified: March 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; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: D153-P516