| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Ear, nose and throat diseases [C09] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
•To evaluate the relative safety and tolerability of three different dose levels of BM32 compared to placebo.
•To assess the minimum effective dose after three subcutaneous injections of different dose levels of BM32 as compared to placebo. The effects of different dose levels of BM32 compared to placebo are evaluated by the grass pollen-specific Total Nasal Symptom Score (TNSS – nasal obstruction, rhinorrhoea, itchy nose and sneezing) of grass pollen-induced allergic rhinitis provoked by spending 6h in the VCC at screening and 6h in the VCC after the last injection (Visit 8) of the treatment |
|
| E.2.2 | Secondary objectives of the trial |
-To determine the effects of vaccination with BM32 versus placebo on allergen-specific antibody responses and on allergy related immunological parameters
- To evaluate the effects of different dose levels of BM32 compared to placebo by grass pollen spec. TNNSS, (TOSS & OSS) and by evaluating the Global Symptom Score (Total Nasal Symptom Score (TNSS) and Total Non-Nasal Symptom Score (TNNSS) combined) of provoked grass pollen-induced allergic rhinitis
- To determine the effects of vaccination with BM32 versus placebo on allergen-specific skin responses by titrated skin prick testing (SPT)
-To evaluate the effects of different dose levels of BM32 compared to placebo by the mean cross-sectional area (MCA) using anterior rhinomanometry (NAR)
-To evaluate the effects of different dose levels of BM32 compared to placebo by FEV1 and FEV1/FVC |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The subject is 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 deemed by the Investigator or designee.
Male or female between 18 and 60 years of age inclusive, at the time of signing the informed consent. They have a history of seasonal allergic rhinitis (SAR) to grass pollen.
They have a normal electrocardiogram without clinically significant abnormalities deemed by the Investigator or designee.
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 (wheal diameter 3mm) for grass pollen at or within 12 months preceding the screening visit.
They have a positive RAST (class greater/equal 2) for timothy grass pollen (g6) and to rPhl p 1+rPhl p 5 at or within 12 months preceding the screening visit.
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
|
|
| E.4 | Principal exclusion criteria |
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.
The subject has received SIT for grass pollen allergy in the last two years prior to this study.
Past or present disease, which as judged by the investigator, may affect the outcome of this study.
autoimmune diseases, immune defects including immuno-suppression, immune-complex-induced immunopathies
Suspected hypersensitivity to any ingredients of the study medication
Use of prohibited medication prior to Screening and throughout the study:
o Depot corticosteroids – 12 weeks
o Oral corticosteroids – 8 weeks
o Inhaled corticosteroids – 4 weeks
The subject is at risk of non-compliance with the study procedures/restrictions.
Allergic symptoms at the time of screening
Any other reason that the Investigator considers makes the subject unsuitable to participate.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Difference in the total Nasal Symptom Score (TNSS) (nasal obstruction, rhinorrhoea, itchy nose and sneezing) between spending 6h in the VCC at screening and spending 6h in the VCC 4 weeks after the last injection of the treatment (Visit 8).
•Frequency of AEs concerning occurrence, seriousness, intensity and drug-relationship.
•Frequency of local reactions (injection site reactions) and systemic reactions classified by a grading scheme according to the Position Paper of the German Society for Allergology and Clinical Immunology
|
|
| E.5.2 | Secondary end point(s) |
•Difference in the Total Non-Nasal Symptom Score TNNSS (TOSS and OSS) between the 6h spent in the VCC at screening and the 0-6h period spent in the VCC 4 weeks after the last injection of the treatment (Visit 8).
•Difference in the Global Symptom Score (TNSS and TNNSS) between the 6h spent in the VCC at screening and the 0-6h period spent in the VCC 4 weeks after the last injection of the treatment (Visit 8).
• Difference in the nasal airflow resistance (NAR) (measured using active anterior rhinomanometry) between the 6h spent in the VCC at screening and the 0-6h period spent in the VCC 4 weeks after the last injection of the treatment (Visit 8).
•Change in skin reaction to grass pollen allergens (SPT) before (screening) and after the treatment (visit 7) by dose titration of the grass pollen extract measuring the difference in the sum of wheal areas between these two visits and evaluating the change in the threshold concentration of grass pollen extract necessary to provoke a positive skin reaction (SPT)
•Difference in the FEV1 and FEV1/FVC between Screening and Visit 8
•Administration of rescue medication via total amount of rescue medication needed
•Vital signs and physical examination
• Laboratory : haematology, biochemistry, and urinalysis at screening, medication phase and at the follow-up examination.
Immunogenicity:
•Change in allergen specific total IgG levels after 3 s.c. injection with BM32, as measured at screening and visit 7
•Change in allergen specific IgE levels after 3 s.c. injection with BM32, as measured at screening and visit 7
•Change in allergy related immunological parameters (T-cell responses and cytokine responses to recombinant allergens, grass pollen extract, BM32 components, and the carrier (PreS), as well as the sensitivity to recombinant grass pollen allergens and timothy grass pollen extract in allergen-induced basophile activation and in the CD203c assay) levels after 3 s.c. injection with BM32, as measured in blood or serum samples collected at screening (Baseline) and after the last injection of the treatment (visit 7) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of the trial is defined as data base lock. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
Print
