Effect of the Interferon Alpha Citizen by Sub-Lingual Way on the Humoral Immunizing Answer

NCT ID: NCT00647465

Last Updated: 2008-03-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2008-03-31

Brief Summary

Influenza vaccination reduces the morbidity and mortality associated with influenza infection in at risk groups including the elderly and individuals with an impaired immune response, but is not totally protective in all recipient. Cytokines including type I interferons are known to play a key role in the innate immune response to virus infection and in the induction of the primary adaptive-immune response. Thus, we evaluated the safety of sublingual administration of IFNa and its effect on immune response to influenza vaccination in a randomized double-blind placebo controlled study in elderly institutionalized individuals.

Detailed Description

The protection afforded by the commonly used influenza sub-unit vaccines is thought to be due principally to the production of antibodies to viral haemagglutinin. The haemagglutination inhibitory (HAI) antibody titer is generally used as a surrogate marker of protection and a HAI antibody titer of 1:40 or greater is considered to confer protection. This is attained, however, in only 50% of elderly subject. Thus, there is an unmet need for an effective non-toxic adjuvant capable of enhancing the antibody response to influenza and other vaccines. Type I IFNs have been shown to induce B-lymphocytes to differentiate into antibody producing plasma cells and to be necessary for the production of both specific and polyclonal IgGs in response to influenza infection. Furthermore, type I IFNs increase the primary antibody response to a soluble antigen in vivo, and increase the production of all IgG sub-classes. Type I IFNs play a key role in adjuvant-induced Th1 responses. Thus, we evaluated the safety of sublingual administration of IFNa and its effect on immune response to influenza vaccination.Institutionalized subjects, aged 75 or more, were randomly assigned to two groups to receive in a double-blind fashion either 107 IU of Intron ATM in 1 ml of isotonic saline or 1 ml of saline alone (placebo) administered sublingually. Interferon or placebo were retained in the mouth for at least 30 seconds prior to ejection. All subjects were then vaccinated, within 30 minutes, with a single intramuscular injection (im) of influenza vaccine (InfluvacTM, Solvay Pharma, France).

The primary objective of this study is to compare the immunogenicity percentage of subjects who increased up to 4 fold their HAI antibody titer at day 21) obtained in the IFN treated group relative to the placebo treated group.

The secondary objectives are to compare mean HAI antibodies titers obtained in the two groups at day 21 ; specific IgG, IgG2a, IgG2a/IgG1 ratio and secretory IgA titers in the 2 groups; specific secretory IgA titers in saliva; durability of protective HAI antibodies titers 3 and 6 months after the vaccination and the safety of sublingual administration of IFNa.

Conditions

Influenza Infection

Keywords

Influenza vaccine; interferon; adjuvant; the elderly

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

1

IFNalpha 2b

Group Type: ACTIVE_COMPARATOR

vaccine

Intervention Type: DRUG

IFNalpha 2b

2

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

vaccine

IFNalpha 2b

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Influenza vaccination

Eligibility Criteria

Inclusion Criteria

• Subjects aged 75 or more, -institutionalized-
• Subjects who were informed of the objectives of the study and who have given their written consent.
• Subjects who have received at least one prior influenza vaccination in the previous 5 years.
• Subjects who should be vaccinated against influenza during the 2005 vaccination campaign.

Exclusion Criteria

• Individuals with severe disease, including neoplasia, autoimmune disease, or type I diabetes
• concomitant treatment with glucocorticoid or immunosuppressive drugs splenectomy or tonsillectomy
• or incapacity to open the mouth

• Minimum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Orakine Ltd, Dublin, Ireland

UNKNOWN

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Department Clinical Research of Developpement

Principal Investigators

Frederic Bloch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1 AP-HP

Locations

Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1

Paris, , France

Countries

France

Other Identifiers

P050601

Identifier Type: -

Identifier Source: org_study_id