Safety and Dose Finding Trial of BM32 in Subjects Suffering From Grass Pollen Allergy

Safety and Dose Finding Study Based on the Effects of Three Subcutaneous Injections of BM32, a Recombinant Hypoallergenic Grass Pollen Vaccine, on Responses to Allergen Challenge by Skin Testing and in the Vienna Challenge Chamber (VCC) as Well as Immunological Response in Subjects Know to Suffer From Grass-pollen Induced Allergic Rhinitis

The study will evaluate the dose response of immunotherapy against grass pollen allergy using the recombinant grass pollen vaccine BM32. Efficacy will be analyzed by:

• skin prick testing
• grass pollen inhalation challenge
• antibody responses. In addition, the safety of subcutaneous application of BM32 will be evaluated.

Study Overview

• Status: Completed
• Conditions: Grass Pollen Allergy
• Intervention / Treatment: Biological: BM32; Biological: BM32; Biological: BM32; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1150
    • Allergy Center Vienna West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• History of seasonal allergic rhinitis from grass pollen
• Normal electrocardiogram
• Moderate to severe response to approx. 1500 grass pollen grains/m3 after 2 hrs of exposure in challenge chamber
• Positive skin prick test for grass pollen at or within 12 months preceding screening visit
• Positive RAST (class 2 or higher) for timothy grass pollen and to rPhl p 1 + rPhl p 5 at or within 12 months preceding screening visit

Exclusion Criteria:

• Pregnant or lactating females
• Females with childbearing potential not using medically acceptable birth control
• Structural nasal abnormalities, nasal polyposis, history of frequent nosebleeds, recent nasal surgery or ongoing upper respiratory tract infection
• Any respiratory disease other than mild asthma controlled with occasional short acting beta agonists and normal lung function
• Current or recent participation in another clinical trial
• SIT for grass pollen allergy in the last two years prior to study
• Past or present disease, which may affect outcome of the trial, judged by investigator
• Autoimmune diseases, immune defects including immunosuppression, immune- complex immunopathies
• Suspected hypersensitivity to any ingredients of study medication
• Use of prohibited medication prior to screening and throughout study
• depot corticosteroids (12 weeks)
• oral corticosteroids (8 weeks)
• inhaled corticosteroids (4 weeks)
• Allergic symptoms at the time of screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BM32 low dose; 3 subcutaneous injections of 10 micrograms in a time span of 8 weeks	Biological: BM32; Subcutaneous injection of 10 micrograms each of the BM32 components adsorbed on 0.3 mg of aluminum hydroxide every 4 week for a total of 3 injections; Biological: BM32; Subcutaneous injection of 20 micrograms of each of the BM32 components adsorbed on 0.6 mg of aluminum hydroxide every 4 weeks for a total of 3 injections; Biological: BM32; Subcutaneous injection of 40 micrograms of each of the BM32 components adsorbed on 1.2 mg of aluminum hydroxide every 4 weeks until a total of 3 injections
Experimental: BM32 medium dose; 3 subcutaneous injections of 20 micrograms in a time span of 8 weeks	Biological: BM32; Subcutaneous injection of 10 micrograms each of the BM32 components adsorbed on 0.3 mg of aluminum hydroxide every 4 week for a total of 3 injections; Biological: BM32; Subcutaneous injection of 20 micrograms of each of the BM32 components adsorbed on 0.6 mg of aluminum hydroxide every 4 weeks for a total of 3 injections; Biological: BM32; Subcutaneous injection of 40 micrograms of each of the BM32 components adsorbed on 1.2 mg of aluminum hydroxide every 4 weeks until a total of 3 injections
Experimental: BM32 high dose; 3 subcutaneous injections of BM32 over a time span of 8 weeks	Biological: BM32; Subcutaneous injection of 10 micrograms each of the BM32 components adsorbed on 0.3 mg of aluminum hydroxide every 4 week for a total of 3 injections; Biological: BM32; Subcutaneous injection of 20 micrograms of each of the BM32 components adsorbed on 0.6 mg of aluminum hydroxide every 4 weeks for a total of 3 injections; Biological: BM32; Subcutaneous injection of 40 micrograms of each of the BM32 components adsorbed on 1.2 mg of aluminum hydroxide every 4 weeks until a total of 3 injections
Placebo Comparator: Placebo; 3 subcutaneous injections over a time span of 8 weeks	Biological: Placebo; Subcutaneous injection of 1.2 mg of aluminum hydroxide suspension every 4 weeks until 3 injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum effective dose for reduction of total nasal symptom score (TNSS) after inhalation challenge with grass pollen	Difference in the total Nasal Symptom Score (TNSS) between spending 6 hrs in the Vienna Challenge Chamber (VCC) at screening and spending 6 hrs in the VCC four weeks after the last subcutaneous injection of BM32.	Baseline and 14 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Minimum Effective dose for reduction of Total Non-Nasal Symptom Score (TNNSS) following inhalation challenge with grass pollen	Baseline and 14 weeks
Minimum effective dose for reduction of Global symptom Score upon inhalation challenge with grass pollen	Baseline and 4 weeks after final s.c. injection
Minimum effective dose for reduction of nasal airflow resistance after inhalation challenge with grass pollen	Baseline and 14 weeks
Minimum effective dose to reduce skin reaction to grass pollen allergen upon skin prick testing	Baseline and 14 weeks
Difference in FEV1 and FEV/FVC between screening and completion of vaccination	Baseline and 14 weeks
Frequency of local reactions to treatment	average of 8 weeks from 1st to last injection
Change in allergy specific total IgG	Baseline and average of 12 weeks after randomization
Change in allergy specific IgE	Baseline and average of 12 weeks after randomization
Frequency of systemic reactions to treatment	average of 8 weeks from 1st to last injection
Severity of local reactions to treatment	Average of 8 weeks from 1st to last injection
Severity of systemic reactions to treatment	Average of 8 weeks from 1st to last injection
Frequency of adverse events	average of 14 weeks from 1st injection

Collaborators and Investigators

• Sponsor: Biomay AG

Publications and helpful links

General Publications

• Zieglmayer P, Focke-Tejkl M, Schmutz R, Lemell P, Zieglmayer R, Weber M, Kiss R, Blatt K, Valent P, Stolz F, Huber H, Neubauer A, Knoll A, Horak F, Henning R, Valenta R. Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy. EBioMedicine. 2016 Sep;11:43-57. doi: 10.1016/j.ebiom.2016.08.022. Epub 2016 Aug 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 26, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 3, 2011

Study Record Updates

• Last Update Posted (Estimate): January 14, 2013
• Last Update Submitted That Met QC Criteria: January 10, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: immunotherapy; grass pollen allergy; recombinant vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Nose Diseases; Rhinitis, Allergic; Rhinitis; Hypersensitivity; Rhinitis, Allergic, Seasonal
• Other Study ID Numbers: CS-BM32-002; 2011-003368-64 (EudraCT Number)