Immune Response of Individuals Vaccinated With Hypoallergenic Derivatives of the Major Birch Pollen Allergen, Bet v 1

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Medical University of Vienna.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Allergy Centre Vienna West
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01353924
First received: May 9, 2011
Last updated: May 12, 2011
Last verified: April 2011
  Purpose

The only disease-modifying treatment for allergic disorders nowadays is allergen-specific immunotherapy (SIT). To induce hyporesponsiveness increasing doses of the disease-eliciting allergens are applied. One major problem of this treatment is, that it has to combat with an already established immune response against the disease-eliciting allergen. To circumvent this problem the investigators want to perform the proof of principle study towards prophylactic treatment. Prophylactic vaccination is used since many years for many infectious diseases. The investigators want to adopt this successful principle for the treatment of type I allergies.

For this purpose non-allergic healthy individuals will be immunized with adjuvant-bound hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. As usual for allergen-specific immunotherapy, injections will be applied subcutaneously. Three injections in one-monthly intervals will be given to establish the immune response and a further injection after one year will determine how the vaccine-induced immune response can be boosted.

The vaccine will be composed of an equimolar mixture of two adjuvant-bound hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. The first investigational product (IP) designated as Bet v 1aF1 is a protein of 73 amino acid residues and represents the first half (1-73aa) of the Bet v 1 molecule. The second IP, Bet v 1aF2, is a protein of 86 amino acid residues and represents the second half (74-160aa) of Bet v 1. Both proteins are expressed in Escherichia coli. The hypoallergenic derivatives lost their IgE binding capacities by the disruption of the conformational IgE epitopes of the Bet v 1 molecule.

In several preclinical and clinical studies it has been shown that the two hypoallergenic fragments, Bet v 1aF1 and Bet v 1aF2 have a strongly reduced allergenic reactivity and almost no sensitization potential, requisite for a prophylactic treatment. In a multi-centre placebo-controlled double blind clinical trial including 124 allergic patients no relevant sensitization against new epitopes could be observed after vaccination of the Alum-bound Bet v 1 derivatives.

In contrast, the vaccine induced a strong IgG response in animals as well as in clinical studies. Vaccine-induced antibodies showed protective properties as they could inhibit the binding of allergic patients' IgE. An improvement of clinical symptoms and a reduction of the skin reactivity was correlated with an increase of IgG antibodies and could be shown only in actively treated patients in a multi-centre placebo-controlled double blind clinical trial.

The investigational products will be tested in a Phase I clinical trial for prophylactic allergy vaccination in healthy non-allergic subjects. The two IPs will be coupled either to Alum and an equimolar mixture will be injected subcutaneously. The immune responses will be compared to placebo. In total 20 non-allergic healthy male subjects (10 per group) will be included in this clinical trial. For safety precautions the subjects will be monitored by skin prick testing using the two uncoupled IPs and commercial birch pollen extract in short intervals to recognize possible vaccine-induced sensitizations. The primary endpoint of phase I clinical trial is the evolution of Bet v 1-specific and Bet v 1 fragment-specific IgG1-4, IgE and IgM antibody levels in serum and in nasal fluids after vaccination of rBet v 1 derivatives.


Condition Intervention Phase
Allergy
Biological: Bet v 1aF1-Alum + Bet v 1aF2-Alum
Biological: Alum-Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Immune Response of Individuals Vaccinated With Hypoallergenic Derivatives of the Major Birch Pollen Allergen, Bet v 1

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Evolution of Bet v 1-, and Bet v 1- fragments -specific total serum IgG antibody levels after vaccination with the Bet v 1-derivatives. [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: No ]
    Measurement of vaccination-induced Bet v 1-, and Bet v 1- fragments -specific serum IgG antibody


Secondary Outcome Measures:
  • Evolution of Bet v 1-, and Bet v 1- fragments -specific serum IgM, IgA, IgE and IgG1-4 antibody levels after vaccination with the Bet v 1-derivatives [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: Yes ]
    Measurement of vaccination-induced Bet v 1-, and Bet v 1- fragments -specific serum IgM, IgA, IgE and IgG1-4 antibody levels

  • Evolution of Bet v 1-, and Bet v 1- fragments -specific IgM, IgA, IgE and IgG1-4 antibody levels after vaccination with the Bet v 1-derivatives in nasal fluids [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: Yes ]
    Measurement of vaccination-induced Bet v 1-, and Bet v 1- fragments -specific IgM, IgA, IgE and IgG1-4 antibody levels in nasal fluids

  • Identification of epitope-specificity and magnitude of the immune response and its possible dependence on the subjects' HLA background [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: No ]
  • Determination of the capacity of treatment-induced antibodies to inhibit the binding of IgE from Bet v 1-sensitized patient to Bet v 1 wildtype. [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: No ]
  • Determination if vaccination with hypoallergenic Bet v 1 derivatives induces skin reactivity to natural, birch pollen-derived Bet v 1 by skin prick testing [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: Yes ]
  • Identification of the type and epitope specificity of the cellular immune responses (Th1/Th2/T regulatory cell development) and the cytokine profile in vaccinated individuals [ Time Frame: after 12 months and after 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: August 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bet v 1aF1 + Bet v 1aF2 -Alum Biological: Bet v 1aF1-Alum + Bet v 1aF2-Alum
subcutaneous injection of equimolar mixture (20µg each) of Bet v 1aF1-Alum and Bet v 1aF2-Alum, three times in monthly intervals and a booster injection after one year
Placebo Comparator: Alum-Placebo Biological: Alum-Placebo
subcutaneous injection of Alum-Placebo, three times in monthly intervals and a booster injection after one year

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age: 18 to 50 years
  2. Male
  3. No history of allergy
  4. Negative skin prick tests for birch pollen and Bet v 1-fragments
  5. Negative IgE for birch pollen and rBet v 1, mugwort pollen house dust mite, cat, alder pollen, hazel pollen, timothy grass pollen
  6. Healthy individuals according to history, physical examination and routine laboratory findings
  7. Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form
  8. Available to complete the study

Exclusion Criteria:

  1. History of drug or other allergy
  2. Autoimmune disease, immune-defects including immuno-suppression, immune complex-induced immunopathies
  3. Contra-indication for adrenaline
  4. Long-term treatment with systemic corticosteroids, immunosuppressive drugs, tranquilizers or psychoactive drugs
  5. Active tuberculosis
  6. Multiple sclerosis
  7. Severe psychological disorders
  8. The subject has participated in a study involving an investigational drug within 90 days prior to visit 1
  9. The subject is concurrently and within 6 months participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug
  10. The subject has donated a unit of blood (450ml) within the previous three months
  11. Has a positive history for human immunodeficiency virus (HIV) antibodies or active hepatitis B or C
  12. The subject is at risk of non-compliance with the study procedures/restrictions
  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: NCT01353924

Contacts
Contact: Katharina Marth, MD +43140400 ext 5111 katharina.marth@meduniwien.ac.at

Locations
Austria
Allergiezentrum Wien West Not yet recruiting
Vienna, Austria, 1150
Contact: Friedrich Horak, MD    +43676842135219      
Principal Investigator: Friedrich Horak, MD         
Medical University of Vienna, Department of Pathophysiology Not yet recruiting
Vienna, Austria, 1090
Contact: Katharina Marth, MD    +43140400 ext 5111    katharina.marth@meduniwien.ac.at   
Sub-Investigator: Katharina Marth, MD         
Principal Investigator: Rudolf Valenta, MD         
Sponsors and Collaborators
Medical University of Vienna
Allergy Centre Vienna West
Investigators
Principal Investigator: Friedrich Horak, MD Allergiezentrum Wien West
Study Director: Rudolf Valenta, MD Medical University of Vienna
  More Information

Publications:
Responsible Party: Friedrich Horak, MD, Allergiezentrum Wien West
ClinicalTrials.gov Identifier: NCT01353924     History of Changes
Other Study ID Numbers: 2411.V2.2009, 2009-015611-40
Study First Received: May 9, 2011
Last Updated: May 12, 2011
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
Allergy
Vaccine
rBet v 1
Prevention

ClinicalTrials.gov processed this record on October 30, 2014