Healthy VolunteersPhase 1MANON-05NCT00261001
Safety Study Comparing a Vaccine Transcutaneous Administration to the Intramuscular Route
A Phase 1 study testing Transcutaneous mode of administration and Intramuscular mode of administration in people with Healthy Volunteers and HIV Infection, run by Objectif Recherche Vaccins SIDA at 2 sites in Germany.
Trial summary
The rationale for transcutaneous vaccination is based on the unique ability of cutaneous immune cells, especially Langerhans cells (LCs), to present antigens to the immune system. DCs can be found at high densities in the epidermis and the dermis of human skin, a fraction of which are the epidermal LCs. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, HIV Infection
- What is being tested?
- Transcutaneous mode of administration and Intramuscular mode of administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesGermany
- Study dates
- Oct 2005to Sep 2009
- Phase
- Phase 1
- 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 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Cohort I
- Healthy male volunteers
- Negative HIV test within the last 3 months Cohort II
- HIV infected males
- Positive HIV-serology
- CD4+ counts > 350 cells/mm3 over the last year
Show all 19Show fewer
- CD4 cells nadir >200/mm3
- Plasma HIV RNA < 400cp/ml over the last 6 months
- Efficient antiretroviral treatment with a minimum of three drugs since at least one year
- In addition Patients from both cohorts must meet the following criteria to be eligible for the study:
- Age between 18 and 45 years,
- BMI between 21 - 26,
- Phototype I to IV
- Clinical examination and an interview on their medical history and possible current therapies
- Subjects able to receive vaccine administration by any of the two administration routes,
- Absence of tetanus vaccination within last 4 years,
- Absence of influenza vaccination in the last year,
- Absence of any psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol schedule.
- Written informed consent
Who cannot join
- In both cohorts, if any of the following apply, the subject cannot enter the study:
- Excessive terminal hair growth on the two investigational skin areas used for the transcutaneous mode of vaccination.
- Phototype V-VI
- Acute illness, e.g. fever, infection at screening and/or D0
- Any acute skin affection which may interfere with the trial assessment on the injection site,
- Any allergy or hypersensibility to one of the components of the Investigational Product (egg products, neomycin),
Show all 14Show fewer
- Medical history of allergy or hypersensitization to any ingredient of colorant used in the transcutaneous mode of administration,
- Medical history of skin cancer,
- Any acute or chronic illness which may expose the subject or interfere with results of the trial,
- Use of any topical treatment on the injection site within the last four weeks,
- Use, within the past 3 months, of any topical and systemic treatment that would interfere with assessment and/or investigational treatment (anti-inflammatory drugs, immunosuppressors or any immune modulator agent),
- Prevision of UV sessions or sun exposure 6 weeks prior to the study or during the study period,
- Subjects with current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations.
- Subject being in the exclusion period of a previous clinical trial (1 month.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 10117
Hospital of the Johann Wolfgang Goethe-University Frankfurt am Main
Frankfurt, Frankfurt Am Main, 60590
About this study
Official title: A Randomized Comparative Phase I Study to Evaluate and to Compare the Safety and Immunogenicity of a Transcutaneous Mode of Administration of a Licensed Tetanus/Influenza Vaccine to the Conventional Intramuscular Route of Vaccine Administration in Healthy Volunteers and HIV-infected Patients
The rationale for transcutaneous vaccination is based on the unique ability of cutaneous immune cells, especially Langerhans cells (LCs), to present antigens to the immune system. DCs can be found at high densities in the epidermis and the dermis of human skin, a fraction of which are the epidermal LCs. It is known that strong and efficient immune responses can be induced by targeting vaccines to skin APCs (Glenn 2003, Partidos 2003), e.g. by epicutaneous application of smallpox vaccine on scarified skin. Several obstacles however prevent vaccines from attaining sufficiently high and free concentrations in these target skin DCs.
In this clinical trial we aim at testing the safety and immunogenicity of this new transcutaneous route of vaccine administration, first with a licensed, well-known, safe and highly immunogenic vaccine i.e. Tetagrip® vaccine, which is licensed for subcutaneous (s.c.) and intra-muscular routes (i.m), and to compare the induced vaccine-specific immune responses to those induced with the conventional (i.m) injection. We hypothesize that the transcutaneous application of Tetagrip® in the commercially available standard preparation of 0.5 ml should be capable to induce at least similar antibody and CD4 and/or CD8 T cell responses to both the tetanus and the flu vaccinal antigens.
This Phase I, open label, randomized study is designed to evaluate and to compare the safety and immunogenicity of a transcutaneous mode of Tetanus / Influenza vaccination to the conventional i.m. route of vaccine administration in two cohorts: The cohort I constituted of healthy volunteers and the cohort II of HIV-infected patients in whom the virus is stably controlled by antiretroviral therapy, ensuring an immune competence and a capacity to respond to vaccines.
Read the detailed description
The proposed study aims to translate our current knowledge about vaccinology, immunology of the skin and on transcutaneous penetration of epicutaneously applied active compounds, into the development of more efficient and well tolerated vaccines, and to progress toward an easy-to-apply patch system for transcutaneous application of vaccines.
To that purpose we aim at testing the safety and immunogenicity of a new transcutaneous route of vaccine administration. We propose to test this new route first with a well-known, safe and highly immunogenic vaccine i.e. anti-influenza and tetanus vaccine which is licensed for sub-cutaneous and intra-muscular routes, and to compare the vaccine-specific immune responses induced after transcutaneous administration to the conventional intramuscular (i.m) injection. Seasonal vaccination against influenza is recommended for all individuals at risk for severe flu, including persons above 60 years of age or suffering from chronic diseases and for medical personal. It is also highly recommended at any age to prevent influenza. In addition vaccination against tetanus is mandatory in childhood and requires recall injections every 5 years to protect against the lethal disease caused by the tetanus toxin.
We hypothesize that the transcutaneous application of a licensed anti-influenza-tetanus vaccine in the commercially available standard preparation of 0.5 ml should be capable to induce at least similar antibody and CD4 and/or CD8 T cell responses to both the tetanus and the flu vaccinal antigens.
Tetagrip® vaccine is an approved and commercially available vaccine manufactured by Sanofi-Pasteur, administered in one injection for preventive vaccination of adults against tetanus and influenza. The Tetagrip® vaccine therefore represents a safe and approved test vaccine to evaluate safety and immunogenicity of the mode of administration under investigation.
The long term goal of this strategy is to improve the efficacy of vaccines that are currently encountering major obstacles such as the HIV vaccines, and to develop a non invasive mode of vaccine administration. Results from this study will help establish a standardized study protocol for the application of HIV-vaccines in future clinical trials.
STUDY DESIGN This Phase I, open label, randomized on the vaccine administration route study is designed to evaluate and to compare the safety and immunogenicity of a transcutaneous mode of Tetanus / Influenza vaccination to the conventional i.m. route of vaccine administration in two cohorts: The cohort I constituted of healthy volunteers and the cohort II of HIV-infected patients in whom the virus is stably controlled by antiretroviral therapy, ensuring an immune competence and a capacity to respond to vaccines.
This is a multisite trial and is being conducted in Germany in two clinical centers:
Cohort I:
Charité - Universitätsmedizin Berlin Clinical Research Center for Hair and Skin Physiology Department of Dermatology and Allergy Schumannstr. 20/21 10117 Berlin, Germany.
Cohort II :
Hospital of the Johann Wolfgang Goethe-University Frankfurt am Main HIV Treatment \& Research Unit Department of Internal Medicine II Theodor-Stern-Kai 7 60590 Frankfurt am Main -Germany
- Conditions
- Healthy Volunteers, HIV Infection
- Being tested
- Transcutaneous mode of administration, Intramuscular mode of administration
- Keywords
- Transcutaneous, Vaccination, Safety, Immunogenicity, HIV, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous mode of administrationBiological
Intramuscular mode of administrationBiological
| Study group | Role | What they receive |
|---|---|---|
| Transcutaneous | Experimental | Not described Receives: Biological: Transcutaneous mode of administration |
| Intramuscular | Active comparator | Not described Receives: Biological: Intramuscular mode of administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical local and systemic tolerance to Tetagrip® vaccine administration for both transcutaneous (TC) and intramuscular (i.m) routes of administration .
Secondary outcomes (5)
The protective tetanus and influenza-specific antibodies GMT titers.
The increase in tetanus and influenza specific antibody titers between baseline and day 14 and day 28.
The tetanus and influenza CD4 and CD8 peripheral blood T cells numbers.
The characteristics of vaccine-specific CD4 and CD8 T cell differentiation.
Proportion of responders with protective specific antibodies GMT titers
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2005 (estimated)
- Study startOct 2005
- Primary completionFeb 2006
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Objectif Recherche Vaccins SIDA
- Sponsor type
- University, hospital or other
- Investigators
- Christine Katlama, Professor/MD, Study chair, Objectif Recherche Vaccin SidaUlrike Blume-Peytavi, Professor/MD, Principal investigator, Charite University, Berlin, GermanyBrigitte Autran, Prof/MD/PhD, Study chair, ORVACS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00261001
- Sponsor's protocol ID
- ORVACS 005
- Acronym
- MANON-05
- Status last verified
- Nov 2009
- First submitted
- 1 Dec 2005
- Last updated
- 25 Nov 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Vogt A, Combadiere B, Hadam S, Stieler KM, Lademann J, Schaefer H, Autran B, Sterry W, Blume-Peytavi U. 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin. J Invest Dermatol. 2006 Jun;126(6):1316-22. doi: 10.1038/sj.jid.5700226.
PubMed 16614727Vogt A, Mahe B, Costagliola D, Bonduelle O, Hadam S, Schaefer G, Schaefer H, Katlama C, Sterry W, Autran B, Blume-Peytavi U, Combadiere B. Transcutaneous anti-influenza vaccination promotes both CD4 and CD8 T cell immune responses in humans. J Immunol. 2008 Feb 1;180(3):1482-9. doi: 10.4049/jimmunol.180.3.1482.
PubMed 18209043Combadiere B, Vogt A, Mahe B, Costagliola D, Hadam S, Bonduelle O, Sterry W, Staszewski S, Schaefer H, van der Werf S, Katlama C, Autran B, Blume-Peytavi U. Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS One. 2010 May 26;5(5):e10818. doi: 10.1371/journal.pone.0010818.
PubMed 20520820
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Comparative Phase I Study to Evaluate and to Compare the Safety and Immunogenicity of a Transcutaneous Mode of Administration of a Licensed Tetanus/Influenza Vaccine to the Conventional Intramuscular Route of Vaccine Administration in Healthy Volunteers and HIV-infected Patients
- ClinicalTrials.gov ID
- NCT00261001
- Acronym / sponsor ID
- MANON-05 / ORVACS 005
- Conditions
- Healthy Volunteers, HIV Infection
- Keywords
- Transcutaneous, Vaccination, Safety, Immunogenicity, HIV, Treatment Experienced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Objectif Recherche Vaccins SIDAUniversity, hospital or other
- Study start
- Oct 2005
- Primary completion
- Feb 2006 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 2 Dec 2005 (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.
The rationale for transcutaneous vaccination is based on the unique ability of cutaneous immune cells, especially Langerhans cells (LCs), to present antigens to the immune system. DCs can be found at high densities in the epidermis and the dermis of human skin, a fraction of which are the epidermal LCs. It is known that strong and efficient immune responses can be induced by targeting vaccines to skin APCs (Glenn 2003, Partidos 2003), e.g. by epicutaneous application of smallpox vaccine on scarified skin. Several obstacles however prevent vaccines from attaining sufficiently high and free concentrations in these target skin DCs.
In this clinical trial we aim at testing the safety and immunogenicity of this new transcutaneous route of vaccine administration, first with a licensed, well-known, safe and highly immunogenic vaccine i.e. Tetagrip® vaccine, which is licensed for subcutaneous (s.c.) and intra-muscular routes (i.m), and to compare the induced vaccine-specific immune responses to those induced with the conventional (i.m) injection. We hypothesize that the transcutaneous application of Tetagrip® in the commercially available standard preparation of 0.5 ml should be capable to induce at least similar antibody and CD4 and/or CD8 T cell responses to both the tetanus and the flu vaccinal antigens.
This Phase I, open label, randomized study is designed to evaluate and to compare the safety and immunogenicity of a transcutaneous mode of Tetanus / Influenza vaccination to the conventional i.m. route of vaccine administration in two cohorts: The cohort I constituted of healthy volunteers and the cohort II of HIV-infected patients in whom the virus is stably controlled by antiretroviral therapy, ensuring an immune competence and a capacity to respond to vaccines.
Detailed description
The proposed study aims to translate our current knowledge about vaccinology, immunology of the skin and on transcutaneous penetration of epicutaneously applied active compounds, into the development of more efficient and well tolerated vaccines, and to progress toward an easy-to-apply patch system for transcutaneous application of vaccines.
To that purpose we aim at testing the safety and immunogenicity of a new transcutaneous route of vaccine administration. We propose to test this new route first with a well-known, safe and highly immunogenic vaccine i.e. anti-influenza and tetanus vaccine which is licensed for sub-cutaneous and intra-muscular routes, and to compare the vaccine-specific immune responses induced after transcutaneous administration to the conventional intramuscular (i.m) injection. Seasonal vaccination against influenza is recommended for all individuals at risk for severe flu, including persons above 60 years of age or suffering from chronic diseases and for medical personal. It is also highly recommended at any age to prevent influenza. In addition vaccination against tetanus is mandatory in childhood and requires recall injections every 5 years to protect against the lethal disease caused by the tetanus toxin.
We hypothesize that the transcutaneous application of a licensed anti-influenza-tetanus vaccine in the commercially available standard preparation of 0.5 ml should be capable to induce at least similar antibody and CD4 and/or CD8 T cell responses to both the tetanus and the flu vaccinal antigens.
Tetagrip® vaccine is an approved and commercially available vaccine manufactured by Sanofi-Pasteur, administered in one injection for preventive vaccination of adults against tetanus and influenza. The Tetagrip® vaccine therefore represents a safe and approved test vaccine to evaluate safety and immunogenicity of the mode of administration under investigation.
The long term goal of this strategy is to improve the efficacy of vaccines that are currently encountering major obstacles such as the HIV vaccines, and to develop a non invasive mode of vaccine administration. Results from this study will help establish a standardized study protocol for the application of HIV-vaccines in future clinical trials.
STUDY DESIGN This Phase I, open label, randomized on the vaccine administration route study is designed to evaluate and to compare the safety and immunogenicity of a transcutaneous mode of Tetanus / Influenza vaccination to the conventional i.m. route of vaccine administration in two cohorts: The cohort I constituted of healthy volunteers and the cohort II of HIV-infected patients in whom the virus is stably controlled by antiretroviral therapy, ensuring an immune competence and a capacity to respond to vaccines.
This is a multisite trial and is being conducted in Germany in two clinical centers:
Cohort I:
Charité - Universitätsmedizin Berlin Clinical Research Center for Hair and Skin Physiology Department of Dermatology and Allergy Schumannstr. 20/21 10117 Berlin, Germany.
Cohort II :
Hospital of the Johann Wolfgang Goethe-University Frankfurt am Main HIV Treatment \& Research Unit Department of Internal Medicine II Theodor-Stern-Kai 7 60590 Frankfurt am Main -Germany
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcutaneous | Experimental | Biological: Transcutaneous mode of administration |
| Intramuscular | Active comparator | Biological: Intramuscular mode of administration |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Cohort I
- Healthy male volunteers
- Negative HIV test within the last 3 months Cohort II
- HIV infected males
- Positive HIV-serology
Key exclusion criteria (14 listed)
- Excessive terminal hair growth on the two investigational skin areas used for the transcutaneous mode of vaccination.
- Phototype V-VI
- Acute illness, e.g. fever, infection at screening and/or D0
- Any acute skin affection which may interfere with the trial assessment on the injection site,
- Any allergy or hypersensibility to one of the components of the Investigational Product (egg products, neomycin),
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 |
|---|---|---|
| Transcutaneous mode of administration | Biological | Transcutaneous |
| Intramuscular mode of administration | Biological | Intramuscular |
Primary outcome
Clinical local and systemic tolerance to Tetagrip® vaccine administration for both transcutaneous (TC) and intramuscular (i.m) routes of administration .
5 secondary outcomes
The protective tetanus and influenza-specific antibodies GMT titers.
The increase in tetanus and influenza specific antibody titers between baseline and day 14 and day 28.
The tetanus and influenza CD4 and CD8 peripheral blood T cells numbers.
The characteristics of vaccine-specific CD4 and CD8 T cell differentiation.
Proportion of responders with protective specific antibodies GMT titers
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2009.
- Background: PubMed 16614727Vogt A, Combadiere B, Hadam S, Stieler KM, Lademann J, Schaefer H, Autran B, Sterry W, Blume-Peytavi U. 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin. J Invest Dermatol. 2006 Jun;126(6):1316-22. doi: 10.1038/sj.jid.5700226.
- Results publication: PubMed 18209043Vogt A, Mahe B, Costagliola D, Bonduelle O, Hadam S, Schaefer G, Schaefer H, Katlama C, Sterry W, Autran B, Blume-Peytavi U, Combadiere B. Transcutaneous anti-influenza vaccination promotes both CD4 and CD8 T cell immune responses in humans. J Immunol. 2008 Feb 1;180(3):1482-9. doi: 10.4049/jimmunol.180.3.1482.
- Derived from this study: PubMed 20520820Combadiere B, Vogt A, Mahe B, Costagliola D, Hadam S, Bonduelle O, Sterry W, Staszewski S, Schaefer H, van der Werf S, Katlama C, Autran B, Blume-Peytavi U. Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS One. 2010 May 26;5(5):e10818. doi: 10.1371/journal.pone.0010818.
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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.
Christine Katlama, Professor/MD study chair
Objectif Recherche Vaccin Sida
Ulrike Blume-Peytavi, Professor/MD principal investigator
Charite University, Berlin, Germany
Brigitte Autran, Prof/MD/PhD study chair
ORVACS
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Transcutaneous mode of administration and Intramuscular mode of administration in people with Healthy Volunteers and HIV Infection, run by Objectif Recherche Vaccins SIDA at 2 sites in Germany.
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 19 inclusion and 14 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: finished, as of the sponsor's last update on 25 Nov 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical local and systemic tolerance to Tetagrip® vaccine administration for both transcutaneous (TC) and intramuscular (i.m) routes of administration .. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00261001, which also lists 3 linked publications.
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 25 Nov 2009.