moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen (with or without concomitant mild to moderate persistent asthma)
Conditions
Interventions
Product Name: BM41 160µg/ml
Pharmaceutical Form: Suspension for injection
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use
Trade N
Sponsors
Academic Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent 2. Age =18 = 65 years 3. Moderate to severe birch-pollen-induced AR/ARC of at least 2 years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (Appendix 1) with or without concomitant mild to moderate persistent asthma 4. FEV1>70% for patients with a history of asthma, FEV1>70% or PEF>80% for patients without a history of asthma 5. A positive SPT (mean wheal diameter = 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization 6. A positive TNPT for birch pollen at screening (Lebel score =6) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Clinically relevant co-sensitization (others than hazel, alder and elm) expected during the birch-pollen season. 2. Chronic asthma with an FEV1<70 % of predicted value. 3. History of AIT (SCIT or SLIT) with any allergen within the past 5 years 4. Ongoing AIT (SCIT or SLIT) with any allergen(s) during the study period 5. Current Treatment with VD3 analogue. 6. Vaccination within one week before or during the treatment phase. 7. Immunosuppressive or biological medication (e.g. IL-5, anti-IgE therapy) within the last six months prior to inclusion and up to end of trial (EoT). 8. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs. 9. Uncontrolled asthma or other active respiratory diseases. 10. Active malignancies or any malignant disease during the previous 5 years. 11. Severe uncontrolled diseases that could increase the risk for patients participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders. 12. Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study. 13. Moderate to severe nasal obstructive diseases that preclude a TNPT (e.g., septal deviation, nasal polyps) or nasal/sinus surgery in the last 3 months. 14. Diseases with a contraindication for the use of adrenaline (e.g. hyperthyroidism, glaucoma). 15. Use of systemic steroids within 4 weeks before start of the study and during the study. 16. Treatment with systemic and local ß-blockers. 17. Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or oral contraceptive pill). 18. Alcohol, drug or medication abuse within the past year. 19. Any clinically significant abnormal laboratory parameter at screening. 20. Lack of cooperation or compliance. 21. Any physical or mental condition that precludes administration of SCIT, compliance or participation in a clinical trial. 22. Patients who are students or employees of the institution or 1st grade relatives or partners of the investigators 23. Participation in a clinical trial within 3 months prior to the current trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate safety/tolerability of subcutaneous treatment with BM41 alone, VD3 alone and a simultaneous subcutaneous treatment with BM41 and VD3 in comparison to placebo in patients with moderate to severe allergic rhinitis/rhino-conjunctivitis caused by birch pollen in a pre-seasonal short-term course of SCIT.;Secondary Objective: The secondary objectives include demonstration of clinical efficacy of SCIT with BM41, with BM41+VD3, and with VD3, all three compared to placebo. Efficacy will be analysed for the upper airways by TNPT and PNIF. Moreover, the clinical efficacy of SCIT with BM41, with BM41+VD3, and with VD3, is evaluated on birch seasonal allergic symptoms and medication use, by control of rhinitis symptoms, Health-Related Quality of Life and “well-days/severe days”, compared to placebo. The assessment of serological and cellular immunological changes induced by SCIT with BM41, BM41+VD3, and VD3, compared to placebo, the onset of clinical and immunological changes induced by SCIT with BM41 compared to BM41+VD3, the indentification of predictive and efficacy-associated biomarkers by transcriptomics on nasal brushing, the assessment of the hypoallergenicity of BM41 and possible de-novo sensitization to BM41 by tSPT. In a subset of patients, asthma control will be evaluated during birch pollen season.;Primary end point(s): The primary endpoint is the number of treatment-related systemic reactions (classified in accordance with the WAO-grading system) in the BM41/VD3 treatment group compared to BM41/Placebo2, VD3/Placebo1 and Placebo1/Placebo2 throughout the pre-seasonal treatment course. This will be determined at every visit according to the reports of the patient.;Timepoint(s) of evaluation of this end point: This will be determined at every visit according to the reports of the patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) Visit (V1),V6, V10 and at V12 (after grass/weed pollen seasons). 2) V1,V6, V10 and a at V12 (after grass/weed pollen seasons). 3) Patients will be asked to keep a daily e-diary to collect the CSMS during the birch pollen season 4) The standardized 5 questions will be assessed at baseline V1, during birch pollen-season 2018 at V11 and at the end of the trial (V12). 5) The mini-RQLQ at baseline,during birch pollen-season 2018 and at the end of the trial. The Quality of Life Total Score at baseline, during birch pollen-season 2018 at V11 and at the end of the trial (V12). 6) Daily Diary 7) At V6, V10, V11 and V12 compared to baseline evaluation (V1). 8) At V1, V11 and V12 9) At V1, V6, V10 and V12 ;Secondary end point(s): 1) Reduction of upper airway response to allergen compared to baseline evaluation as assessed by a TNPT after the first maintenance shot. 2) Improvement in nasal patency compared to baseline evaluation (Visit 1) as assessed by Peak Nasal Inspiratory Flow (PNIF) after TNPT after the first maintenance shot. 3) Furthermore, clinical efficacy will be investigated by analyzing the reduction in a combined symptom and medication score (CSMS) in the BM41/VD3 treatment group compared to BM41/Placebo2, VD3/Placebo1 and Placebo1/Placebo2 as assessed during the birch pollen season. The following definition will be used to calculate the CSMS: CSMS = (daily) Symptom Score (dSS) + (daily) Medication Score (dMS) The dSS comprises of six individual symptom scores: four nasal symptoms (Itchy Nose, Sneezing, Runny Nose, Blocked Nose) and two ocular symptoms (Itchy/red eyes, Watery eyes), all daily scored (by patients in e-diaries in the birch pollen season) on a scale from 0-3. The dSS will be calculated as mean of all non-missing daily SS during the birch pollen season (range 0-18) divided by the number of individual symptoms (6 symptoms). As such the dSS has a range from 0-3. The dMS is based on the following score | — |
Countries
Netherlands
Contacts
Public ContactLaurian Jongejan
Academic Medical Center
Outcome results
None listed