Effect of the Interferon Alpha Citizen by Sub-Lingual Way on the Humoral Immunizing Answer (GP-INFA)

This study has been terminated.
(End of the study)
Sponsor:
Collaborator:
Orakine Ltd, Dublin, Ireland
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00647465
First received: March 26, 2008
Last updated: March 28, 2008
Last verified: November 2005
  Purpose

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.


Condition Intervention Phase
Influenza Infection
Drug: vaccine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Randomized Double-Blind Placebo Controlled Study Evaluating the Effect of Sublingual Administration of IFNa on the Immune Response to Influenza Vaccination in Subjects Aged 75 or More.

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Percentage of subjects presenting an increase > 4 fold of antiH1N1 or antiH3N2 or anti-B haemagglutination inhibition antibody titer, 3 weeks following influenza vaccination. [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • geometric mean of haemagglutination antibody titer obtained at day 21 with or without IFNa [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • influenza virus strain-specific IgG total, IgG2a, IgG2a/IgG1 ratio, secretory IgA responses at day 21 in each group . [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • influenza virus strain-specific secretory IgA anti-influenza antibody titers in saliva 14 and 21 days following vaccination. [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • evaluation of individual response to IFNa treatment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • levels of serologic alpha interferon and of anti- alpha -interferon at day 21. [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Percentage of patients maintaining protective antibody titers 3 and 6 months following vaccination. [ Time Frame: 3 months and 6 months after ] [ Designated as safety issue: No ]
  • Predictive factors of vaccine response (age, total lymphocyte cell count, CD4 cell count…) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Evaluation of cellular vaccine response in a subgroup of subjects. [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Enrollment: 140
Study Start Date: October 2005
Study Completion Date: March 2008
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
IFNalpha 2b
Drug: vaccine
IFNalpha 2b
Other Name: Influenza vaccination
Placebo Comparator: 2
Placebo
Drug: Placebo
Placebo
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   75 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00647465

Locations
France
Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1
Paris, France, 75005
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Orakine Ltd, Dublin, Ireland
Investigators
Principal Investigator: Frederic Bloch, MD, PhD Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1 AP-HP
  More Information

No publications provided

Responsible Party: Mathieu QUINTIN, Department Clinical Research of Developpement
ClinicalTrials.gov Identifier: NCT00647465     History of Changes
Other Study ID Numbers: P050601
Study First Received: March 26, 2008
Last Updated: March 28, 2008
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Influenza vaccine
interferon
adjuvant
the elderly

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
Respiratory Tract Diseases
Respiratory Tract Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014