S.C. Immunotherapy With BM41 in Patients With Allergic Rhino-conjunctivitis Caused by Birch Pollen

A Randomized, DBPC Study to Determine the Safety, Tolerability and Immunological Effects of BM41 Compared to Placebo and to Treatment With Standard s.c. Immunotherapy in Patients Allergic to Birch Pollen

The aim of this clinical phase I single centre, randomized, double-blind, placebo-controlled study with open comparator is to investigate tolerability and safety as well as the immunological effects of BM41 in comparison to placebo (double blind) and to a standard subcutaneous immunotherapy Alutard SQ (open) in birch allergic patients.

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Inclusion Criteria:

1. Signed informed consent
2. Age ≥18 ≤ 65 years
3. Moderate to severe birch-pollen-induced allergic rhinitis/rhinoconjunctivitis of at least 2 years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines (Appendix 1, see the manual of procedures) with or without concomitant mild to moderate persistent asthma
4. Forced expiratory volume (FEV1) >70% for patients with a history of asthma, FEV1>70% or peak flow (PEF) >80% for patients without a history of asthma
5. A positive skin prick test (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. Specific IgE against birch pollen extract ≥ 0.7 kU/L and against Bet v 1 ≥ 0.35 kU/L as determined by ImmunoCAP

Exclusion Criteria:

1. Chronic asthma with an FEV1<70 % of predicted value.
2. History of allergen immunotherapy (AIT) (subcutaneous (SCIT) or sublingual (SLIT)) with birch pollen or tree pollen mix including birch pollen within the past 5 years
3. Ongoing AIT (SCIT or SLIT) with any allergen(s) during the study period
4. Vaccination within one week before or during the treatment phase.
5. 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).
6. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
7. Uncontrolled asthma or other active respiratory diseases.
8. Active malignancies or any malignant disease during the previous 5 years.
9. 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.
10. Renal insufficiency
11. Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study.
12. Diseases with a contraindication for the use of adrenaline (e.g. hyperthyroidism, glaucoma).
13. Use of systemic steroids within 4 weeks before start of the study and during the study.
14. Treatment with systemic and local β-blockers.
15. Known allergy towards constituents of the vaccine
16. Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be intrauterine device or hormonal contraception (birth control pill, implant, transdermal patch, vaginal ring or depot injection). It is also accepted, if the female patient is permanently sterile or infertile, if her sole partner is permanently sterile, or if they use both condom and diaphragm, The definition of sterile or infertile is surgically sterilized (vasectomy/bilateral salpingectomy, hysterectomy and/or bilateral ovariectomy) or post menopause defined as a non-menstrual period of at least 12 months before inclusion in the study.
17. Alcohol, drug or medication abuse within the past year.
18. Any clinically significant abnormal laboratory parameter at screening.
19. Lack of cooperation or compliance.
20. Any physical or mental condition that precludes administration of SCIT, compliance or participation in a clinical trial.
21. Patients who are students or employees of the institution or 1st grade relatives or partners of the investigators
22. Participation in a clinical trial within 3 months prior to the current trial.