Effect of Different Pre-seasonal BM32 Dosings on the Induction of a Protective Immune Response

Study to Evaluate the Effect of Different Pre-seasonal BM32 Dosing Schedules on the Rapid Induction of a Protective IgG Immune Response

BM32 is a product for immunotherapy of grass pollen allergies. It consists of 4 different recombinant proteins (BM321, BM322, BM325 and BM326) adsorbed on alhydrogel. This prospective, double-blind. placebo controlled, mono-centric trial investigates the levels of allergen specific IgG antibodies following 3, 4 or 5 subcutaneous injections before the grass pollen season.

Study Overview

• Status: Completed
• Conditions: Hypersensitivity
• Intervention / Treatment: Biological: BM32; Biological: Placebo

Detailed Description

The aim of this study is to further optimize the immunization schedule by

• moving the last injection into beginning of the grass pollen season for all study arms in order to ensure highest possible IgG4 levels when they are needed - i.e. at the peak of the grass pollen season,
• administration of more than 3 pre-seasonal injections in order to build up sufficiently high levels of IgG4 already in the first year of treatment , and
• dosing during the beginning of the grass pollen season to establish safety in this setting The effect of such optimized immunization schedule on the induction of an IgG4 immune response as a surrogate parameter for efficacy will be studied. The Total Nasal Symptom Score (TNSS) before and after the treatment and Combined Symptom-Medication Score (SMS) during the grass pollen season will be evaluated as secondary endpoints. This will allow intra-individual comparison of seasonal symptom data and responsiveness in the chamber setting.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1150
    • Vienna Challenge Chamber

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subjects are grass pollen allergic but otherwise healthy. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, laboratory studies, and other tests.
• They are aged 18 to 60 years inclusive.
• They have a history of seasonal allergic rhinitis (SAR) to grass pollen.
• They have a normal electrocardiogram without clinically significant abnormalities.
• They exhibit a moderate to severe response to approximately 1500 grass pollen grains/m3 after the first 2h in the Vienna Challenge Chamber, which is defined as a nasal symptom score (TNSS) of at least 6. (Nasal symptom score is the sum of nasal obstruction, rhinorrhoea, itchy nose and sneezing, each of which have been scored on a scale from 0 to 3).
• They have a positive skin prick test with a wheal diameter >5mm for grass pollen extract at the screening visit.
• They have a positive serum IgE test for timothy grass pollen and to rPhl p 1+rPhl p 5 at the screening visit (ImmunoCAP ≥3.5 kUA/l; i.e ≥ class 2)..
• There are no conditions or factors which would make the subject unlikely to be able to stay in the chamber for 6 hours.
• They are capable of giving informed consent which includes compliance with the requirements and restrictions listed in the consent form.
• They are available to complete all study measurements

Exclusion Criteria:

• Sensitization to Phl p 7
• Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method (pregnancy to be controlled by a pregnancy dipstick test).
• On examination the subject is found to have any structural nasal abnormalities or nasal polyposis, a history of frequent nosebleeds, recent nasal surgery or ongoing upper respiratory tract infection which in the Responsible Physician's opinion renders the subject unsuitable for participation in the study.
• Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.
• The subject is concurrently participating or has participated in any clinical study in the previous month.
• Participation in a SIT trial for grass pollen allergy in the three years prior to this study.
• Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BM32-3; 2 placebo injections will be given followed by 3 injections with 20 micrograms each of BM321, BM322, BM325 and BM326	Biological: BM32; BM32 is a mixture of 4 different recombinant proteins directed at the major grass pollen allergens, adsorbed on aluminum hydroxide
Experimental: BM32-4; 1 placebo injections will be given followed by 4 injections with 20 micrograms each of BM321, BM322, BM325 and BM326	Biological: BM32; BM32 is a mixture of 4 different recombinant proteins directed at the major grass pollen allergens, adsorbed on aluminum hydroxide
Experimental: BM32-5; 5 injections with 20 micrograms each of BM321, BM322, BM325 and BM326 will be given	Biological: BM32; BM32 is a mixture of 4 different recombinant proteins directed at the major grass pollen allergens, adsorbed on aluminum hydroxide
Placebo Comparator: Placebo; 5 placebo injections (alhydrogel only) will be given	Biological: Placebo; Placebo contains aluminum hydroxide only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Titer of allergen specific IgG4 antibodies	approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total nasal symptom score upon pollen challenge (TNSS)	Sensitivity to a grass pollen challenge in an environmental exposure chamber	Change from baseline at 9 months
Mean daily combined symptom and medication score (SMS)		2 weeks
Well-being via visual analog scale		2 weeks
Titers of allergen specific IgG antibodies		Up to 9 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emerging adverse events	Frequency and severity of IMP related adverse events	up to 9 months

Collaborators and Investigators

• Sponsor: Biomay AG
• Investigators: Principal Investigator: Petra Zieglmayer, MD, Vienna Challenge Chamber GmbH

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: December 17, 2015
• First Submitted That Met QC Criteria: December 30, 2015
• First Posted (Estimate): December 31, 2015

Study Record Updates

• Last Update Posted (Estimate): January 19, 2017
• Last Update Submitted That Met QC Criteria: January 18, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: subcutaneous immunotherapy; Grass pollen allergy; allergy vaccine; dose regimen
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity
• Other Study ID Numbers: CS-BM32-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes