Influenza InfectionPhase 3GP-INFANCT00647465
Effect of the Interferon Alpha Citizen by Sub-Lingual Way on the Humoral Immunizing Answer
A Phase 3 study testing vaccine in people with Influenza Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 75 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza Infection
- What is being tested?
- vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2005to Mar 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 75 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1
Paris, 75005
About this study
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.
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.
Read the 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
- Being tested
- vaccine, Placebo
- Keywords
- Influenza vaccine, interferon, adjuvant, the elderly
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vaccineDrug
Also called Influenza vaccination
IFNalpha 2b
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | IFNalpha 2b Receives: Drug: vaccine |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects presenting an increase > 4 fold of antiH1N1 or antiH3N2 or anti-B haemagglutination inhibition antibody titer, 3 weeks following influenza vaccination.
Measured: 21 days
Secondary outcomes (8)
geometric mean of haemagglutination antibody titer obtained at day 21 with or without IFNa
Measured: 21 days
influenza virus strain-specific IgG total, IgG2a, IgG2a/IgG1 ratio, secretory IgA responses at day 21 in each group .
Measured: 21 days
influenza virus strain-specific secretory IgA anti-influenza antibody titers in saliva 14 and 21 days following vaccination.
Measured: 21 days
evaluation of individual response to IFNa treatment
Measured: 21 days
levels of serologic alpha interferon and of anti- alpha -interferon at day 21.
Measured: 21 days
Percentage of patients maintaining protective antibody titers 3 and 6 months following vaccination.
Measured: 3 months and 6 months after
Predictive factors of vaccine response (age, total lymphocyte cell count, CD4 cell count…)
Measured: 21 days
Evaluation of cellular vaccine response in a subgroup of subjects.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2008 (estimated)
- Study startOct 2005
- Primary completionMay 2006
- Study completionMar 2008
Why it stopped: End of the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza InfectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Orakine Ltd, Dublin, Ireland
- Investigators
- Frederic Bloch, MD, PhD, Principal investigator, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1 AP-HP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00647465
- Sponsor's protocol ID
- P050601
- Acronym
- GP-INFA
- Status last verified
- Nov 2005
- First submitted
- 26 Mar 2008
- Last updated
- 31 Mar 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00647465
- Acronym / sponsor ID
- GP-INFA / P050601
- Conditions
- Influenza Infection
- Keywords
- Influenza vaccine, interferon, adjuvant, the elderly
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End of the study
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Orakine Ltd, Dublin, Ireland
- Study start
- Oct 2005
- Primary completion
- May 2006 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 31 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: vaccineIFNalpha 2b |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| vaccineAlso: Influenza vaccinationIFNalpha 2b | Drug | 1 |
| PlaceboPlacebo | Drug | 2 |
Primary outcome
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
8 secondary outcomes
geometric mean of haemagglutination antibody titer obtained at day 21 with or without IFNa
Time frame: 21 days
influenza virus strain-specific IgG total, IgG2a, IgG2a/IgG1 ratio, secretory IgA responses at day 21 in each group .
Time frame: 21 days
influenza virus strain-specific secretory IgA anti-influenza antibody titers in saliva 14 and 21 days following vaccination.
Time frame: 21 days
evaluation of individual response to IFNa treatment
Time frame: 21 days
levels of serologic alpha interferon and of anti- alpha -interferon at day 21.
Time frame: 21 days
Percentage of patients maintaining protective antibody titers 3 and 6 months following vaccination.
Time frame: 3 months and 6 months after
Predictive factors of vaccine response (age, total lymphocyte cell count, CD4 cell count…)
Time frame: 21 days
Evaluation of cellular vaccine response in a subgroup of subjects.
Time frame: 21 days
Results and safety
The study was stopped early (reason given: End of the study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frederic Bloch, MD, PhD principal investigator
Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Broca-La Rochefoucauld, Service de Gérontologie 1 AP-HP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing vaccine in people with Influenza Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: End of the study). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2008.