Phase II Study of Grass Pollen Allergy Vaccine BM32

Study Overview
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Brief Summary
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The study will evaluate the efficacy and safety of BM32 in grass pollen allergic subjects. It will test the hypothesis that either of two doses of BM32 will lead to a sustained relief off allergy symptoms over a two year study period.

Detailed Description
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The present study is designed to evaluate the efficacy and safety of a treatment with the recombinant vaccine BM32 during two consecutive grass pollen seasons. Efficacy evaluation will be performed on the basis of allergy symptoms and use of relief medication as well as based on immunological parameters. After patient assessment during a screening season, patients will be randomized to one of two doses of BM32 or placebo. Patients will receive three injections of BM32 pre-season and one post-season boost injection to maintain optimal allergen specific IgG responses. Outcome will be measured after both seasons individually.

Official Title
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Phase IIb Study on the Safety and Efficacy of BM32, a Recombinant Hypoallergenic Vaccine for Immunotherapy of Grass Pollen Allergy

Conditions
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Grass Pollen Allergy

Intervention / Treatment
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* Biological: BM32
* Biological: BM32
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive history of grass pollen allergy Positive skin prick test reaction to grass pollen extract Grass pollen specific IgE and rPhl p 1/rPhl p 5 specific IgE (>3 kUA/L) Moderate to severe symptoms of grass pollen allergy during pollen peak Exclusion Criteria: Symptomatic perennial allergies Atopic dermatitis Pregnancy or breast feeding Women with childbearing potential not using medically accepted birth control Autoimmune diseases, immune defects, immune suppression Immune complex induced immunopathies Contra indications for adrenaline Severe general maladies, malignancies Patients on long-term systematic corticosteroids, immune suppressive drugs, tranquilizers or psychoactive drugs Contra indication for skin prick testing Bronchial asthma not controlled by low dose inhaled corticosteroids Chronic use of beta blockers Participation in another clinical trial within one month prior to study Participation in SIT trial in 2 years prio to study Patients who had a previous grass pollen SIT Risk of non-compliance with study procedures Use of prohibited medications Depot corticosteroids - 12 weeks prior to enrolment Oral corticosteroids - 8 weeks prior to enrolment High dose inhaled corticosteroids - 4 weeks prior to enrolment Use of H1 antihistamines 3 days prior to enrolment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BM32 low dose<br>7 subcutaneous injections of 20 micrograms over two grass pollen seasons | Biological: BM32<br>* Subcutaneous injection of 20 micrograms of each of the protein components of BM32 adsorbed on 0.6 mg of aluminum hydroxide every 4 weeks for a total of 3 injections before each pollen season and one boost injection after pollen season<br>|
| Experimental: BM32 high dose<br>7 subcutaneous injections of 40 micrograms over two grass pollen seasons | Biological: BM32<br>* Subcutaneous injection of 40 micrograms of each of the protein components of BM32 adsorbed on 1.2 mg of aluminum hydroxide every 4 weeks for a total of 3 injections before each pollen season and one boost injection after pollen season<br>|
| Placebo Comparator: Placebo<br>7 subcutaneous injections over a time span of two pollen seasons | Biological: Placebo<br>* Subcutaneous injection of 1.2 mg of aluminum hydroxide suspension every four weeks before each pollen season and one injection after pollen season for a total of 7 injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean daily combined symptom medication score (SMS)during the peak of the pollen season. | The score will be recorded daily for the 30-45 days with the highest pollen count in each center | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital functions |  | Up to 22 months | 
| Safety laboratory hematology |  | up to 22 months | 
| Meal level of well-being measured by a visual analog scale (VAS) during grass pollen season | The VAS will be recorded daily during the grass pollen seasons of 2013 and 2014 | Up to 8 months | 
| Number of bad days during the peak pollen season and the whole pollen season | The number of bad days will be recorded daily during the grass pollen seasons of 2013 and 2014 | Up to 8 months | 
| Number of symptom-free days during the peak pollen season and the whole pollen season | The mesure will be recorded daily during the grass pollen seasons of 2013 and 2014 | Up to 8 months | 
| Rhinoconjunctivitis quality of life evaluation by RQLQ questionnaire during pollen season | The questionnaire will be completed on a weekly basis during the pollen seasons of 2013 and 2014. | Approx. 22 months | 
| Mean asthma score during pollen season | The score will be recorded on a daily basis duirng the pollen seasons of 2013 and 2014 | Up to 8 months | 
| Mean allergy specific IgG and IgE antibodies before and after vaccination | These antibody levels will be recorded a total of five times (01/2013, 04/2013, 09/2013, 01/2014 and 04/2014) | Up to 16 months | 
| Mean daily symptom and medication score during the whole pollen season | The score will be recorded daily approximately during May 2013 - August 2013 and May 2014 - August 2014 | Up to 8 months | 
| Mean daily symptom score (SS) and medication score (MS) during the peak pollen season and the whole pollen season | The scores will be recorded daily during the pollen seasons of 2013 and 2014 | Up to 8 months | 
| Skin reactivity to grass pollen extract by titrated skin prick testing | The titrated skin prick testing will be applied a total of 4 times before and after the pollen seasons of 2013 and 2014. | Up to 15 months | 
| Results of physical examination |  | up to 22 months | 
| Safety Laboratory: Blood biochemistry |  | Up to 22 months | 
| Safety laboratory: Urine analysis |  | up to 22 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Grass pollen allergy, Immunotherapy, Recombinant vaccine, Rhinitis, allergic, seasonal