Clinical trial NCT04912076: S.C. Immunotherapy With BM41 in Patients With Allergic Rhino-conjunctivitis Caused by Birch Pollen
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Birch Pollen Allergy
Allergic Rhinoconjunctivitis
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Biomay AG
name: European Commission
name: University of Salzburg
First posted: 2021-06-03
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled, single centre Phase I study with an open comparator group
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Please see original article.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events with emphasis on allergic reactions. Safety/tolerability of subcutaneous treatment with BM41 compared to placebo (double-blind) and to a conventional standardized birch pollen extract in patients with birch pollen allergy
timeFrame: Through study completion, an average of 4 months
Secondary outcomes:
measure: Changes in serum immunoglobulin E (IgE), immunoglobulin G (IgG) and immunoglobulin G4 (IgG4) levels.
timeFrame: Day 7, 42 and 126
measure: Epigenetic changes induced by BM41 and Alutard compared to placebo
timeFrame: Day 7, 42 and 126
measure: Changes in wheal sizes upon titrated skin prick test with BM41.
timeFrame: Day 7, 42 and 112
measure: Changes in the capacity to block IgE facilitated allergen binding and histamine release.
timeFrame: Day 7, 42 and 126
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense Research Center for Anaphylaxis, Odense University Hospital
Study officials:
affiliation: Odense research Center for Anaphylaxis, Odense University Hospital, Denmark
name: Carsten Bindslev-Jensen, Professor
role: PRINCIPAL_INVESTIGATOR
References: