Safety Study Comparing a Vaccine Transcutaneous Administration to the Intramuscular Route

NCT00261001 | Completed Phase 1

• 1 other identifier: ORVACS 005
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Healthy Volunteers; HIV Infection

Keywords

Transcutaneous; Vaccination; Safety; Immunogenicity; HIV; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Transcutaneous

EXPERIMENTAL

Biological: Transcutaneous mode of administration

Intramuscular

ACTIVE COMPARATOR

Biological: Intramuscular mode of administration

Interventions

Transcutaneous mode of administration BIOLOGICAL

Transcutaneous

Intramuscular mode of administration BIOLOGICAL

Intramuscular

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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,

You may not qualify if:

• 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),
• 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.

Sponsors & Collaborators

• Objectif Recherche Vaccins SIDA: lead

Study Sites (2)

Hospital of the Johann Wolfgang Goethe-University Frankfurt am Main

Frankfurt, Frankfurt Am Main, 60590, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

Location

Related Publications (3)

• 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.

  PMID: 16614727 BACKGROUND

• Vogt 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.

  PMID: 18209043 RESULT

• Combadiere 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.

  PMID: 20520820 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Christine Katlama, Professor/MD

  Objectif Recherche Vaccin Sida

  STUDY CHAIR

• Ulrike Blume-Peytavi, Professor/MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Brigitte Autran, Prof/MD/PhD

  ORVACS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 1, 2005
• First Posted: December 2, 2005
• Study Start: October 1, 2005
• Primary Completion: February 1, 2006
• Study Completion: September 1, 2009
• Last Updated: November 25, 2009

Record last verified: 2009-11

Locations

DE (2)