Phase II Study to Investigate the Kinetics of the Immune Response Generated by Influenza Virus Vaccine.

Influenza Clinical Trial

Official title:

A Randomized, Open-Label, Placebo-Controlled Trial to Investigate the Kinetics of the Immune Responses Elicited by a Liquid Formulation of Influenza Virus Vaccine, Trivalent,Types A & B, Live, Cold-Adapted (CAIV-T) in Healthy Adults Aged 18 to <65 Years.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00192309
• Other study ID #: D153 P004
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: February 13, 2012
• Start date: September 2001
• Est. completion date: December 2001

Study information

• Verified date: February 2012
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to perform a variety of assays on blood, serum, nasal wash and cell samples obtained from healthy adult subjects for the purposes of developing assays for application in the further investigation of immune responses generated by influenza virus vaccine, trivalent, types A & B, live, cold-adapted (liquid formulation CAIV-T; Wyeth, Marietta, PA).

Description:

This was a randomized, open-label, placebo-controlled, outpatient study carried out in healthy adults 18 to < 65 years of age. The study was designed to evaluate the kinetics of the immune responses generated by each of the study products in order to determine the best sampling time for future studies. Subjects were randomized in a 1:1:1 ratio to receive a single dose of either CAIV-T, inactivated influenza virus vaccine (TIV), or placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2001
• Est. primary completion date: December 2001
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subjects had to have been at least 18 years of age and less than 65 years of age at the time informed consent was obtained;

• Women of child-bearing potential had to use reliable methods of hormonal and/or nonhormonal contraception (which includes cervical cap, diaphragm, condoms with spermicide or IUD) during sexual intercourse throughout the entire study period; a negative urine pregnancy test (with detection limit of less than or equal to 25mIU/mL) no more than 24 hours prior to vaccine administration; and agreed to avoid pregnancy during participation in the study. A urine pregnancy test was also conducted at the completion of study participation. Females who were surgically sterile at time of enrollment were not required to undergo pregnancy testing.

• who were determined by medical history, physical examination and clinical judgement to be eligible for the study.

• who provided written informed consent after the nature of the study has been explained;

• who were available for one month duration of the trial (from enrollment to study completion);

• who could be reached by study staff for the post-vaccination contact [telephone, clinic or home visit].

Exclusion Criteria:

• who were perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;

• with a known or suspected disease of the immune system or those receiving immunosuppressive therapy, including systemic corticosteroids and intranasal steroids; or cytotoxic agents;

• who had an immunosuppressed or an immunocompromised individual living in the same household;

• who had a documented history of hypersensitivity to egg or egg protein or any other component of the study vaccine or placebo;

• who received any commercially-available or investigational injected influenza vaccine in the 6 months prior to enrollment, or a non-study influenza vaccine since enrollment;

• who previously received an intranasally administered influenza vaccine;

• who had any medical conditions that, in the opinion of the investigator, might interfere with interpretation of the study results;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• CAIV-T
Liquid CAIV-T vaccine for this study consisted of three cold-adapted, attenuated, reassortant strains representing the hemagglutinin (HA) and neuraminidase (NA) antigens of the A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) and B/Yamanashi/166/98 influenza virus strains. The reassortant vaccine strains were grown in specific pathogen-free (SPF) eggs and the allantoic fluid, which contained virus, was harvested, concentrated and purified. Each dose of CAIV-T used in this study was formulated to contain approximately 107 FFU of each of the 6:2 influenza reassortant vaccine strains.
• TIV
TIV in this study consisted of Flushield™, manufactured by Wyeth Vaccines, Marietta, PA, USA. Each 0.5 mL dose contained no less than 15 ug of the hemagglutinin antigens from each of the A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Yamanashi/166/98 strains, making TIV in this study antigenically matched to the influenza strains contained in CAIV-T.
• Placebo
Placebo in this study consisted of physiological saline. The total volume of 0.2 mL was administered intranasally with a spray applicator (approximately 0.1 mL into each nostril).

Locations

Country	Name	City	State
United States	David M. Radin, MD	Stamford	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
MedImmune LLC	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kinetics of the hemagglutination inhibition antibody response to each vaccine strain	The geometric mean titers for each strain between Day 0 and 28 were examined.	Day 0-28	No
Secondary	Expression of IgA in nasal wash and saliva swab samples	Nasal wash and saliva swab IgA antibody titers were expressed as the ratio of specific to total IgA.	Days 0-28	No
Secondary	Expression of B-cells in peripheral blood	The B-cell ELISPOT assays are designed to detect B-cells in the peripheral blood that are actively secreting influenza strain-specific IgG or IgA antibody.	Days 0-28	No
Secondary	Number of CD3+ peripheral blood mononuclear cells secreting interferon gamma	The number of CD3+ peripheral blood mononuclear cells (PBMCs), i.e., T-cells, secreting IFN-? prior to and after vaccination following in vitro stimulation of these cells using the IFN-? ELISPOT assay.	Days 0-28	No
Secondary	Number of subjects with local reactions	Local injection site reactions were collected from subjects in the TIV treatment group only.	Days 0-7	Yes
Secondary	Number of subjects with systemic reactions	Each study subject collected prompted reactogenicity events on a diary card worksheet for 7 days (study days 0 - 6) following vaccination.	Days 0-7	Yes
Secondary	Number of subjects with adverse events	An Adverse Event (or Adverse Experience, AE) was any untoward, undesired or unexpected clinical event in the form of signs, symptoms, disease or laboratory or physiological observations occurring (in a human being) in a temporal relationship to the use of a WLV product, regardless of causal relationship.	Days 0-7	Yes