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

NCT04912076 | Completed Phase 1 DMC

• 1 other identifier: 2018-001486-17
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Birch Pollen Allergy; Allergic Rhinoconjunctivitis

Outcome Measures

Primary Outcomes (1)

• 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

  Safety/tolerability of subcutaneous treatment with BM41 compared to placebo (double-blind) and to a conventional standardized birch pollen extract. Number and character of all adverse events will be evaluated.

  Through study completion, an average of 4 months

Secondary Outcomes (4)

• Changes in serum immunoglobulin E (IgE), immunoglobulin G (IgG) and immunoglobulin G4 (IgG4) levels.

  Day 7, 42 and 126

• Epigenetic changes induced by BM41 and Alutard compared to placebo

  Day 7, 42 and 126

• Changes in wheal sizes upon titrated skin prick test with BM41.

  Day 7, 42 and 112

• Changes in the capacity to block IgE facilitated allergen binding and histamine release.

  Day 7, 42 and 126

Study Arms (3)

BM41

EXPERIMENTAL

9 treatment visits where subcutaneous injections with solution of the test drug BM41 (adsorbed to aluminium hydroxide) in a blinded fashion starting with 12.5 nanogram increasing to 20 microgram which is maintenance dose. Subsequently 3 maintenance doses will be given. Please look at the results in the original article.

Drug: BM41

Placebo

PLACEBO COMPARATOR

Placebo consisting of only aluminium hydroxide will be administered blinded in amounts according to BM41.

Other: Placebo

Alutard

ACTIVE COMPARATOR

Alutard SQ (ALK) will serve as the comparator and administration is open. Up-dosing is performed according to the official cluster scheme, reaching maintenance of 100.000 SQ-E

Drug: ALK Alutard SQ Betula verrucosa

Interventions

BM41 DRUG

Subcutaneous injection of increasing doses of BM41

BM41

Placebo OTHER

Subcutaneous injections of placebo containing aluminium hydroxide.

Placebo

ALK Alutard SQ Betula verrucosa DRUG

Subcutaneous injections with increasing doses of Alutard according to cluster up-dosing scheme.

Alutard

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Age ≥18 ≤ 65 years
• 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
• 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
• 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
• Specific IgE against birch pollen extract ≥ 0.7 kU/L and against Bet v 1 ≥ 0.35 kU/L as determined by ImmunoCAP

You may not qualify if:

• Chronic asthma with an FEV1\<70 % of predicted value.
• 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
• Ongoing AIT (SCIT or SLIT) with any allergen(s) during the study period
• Vaccination within one week before or during the treatment phase.
• Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
• Uncontrolled asthma or other active respiratory diseases.
• Active malignancies or any malignant disease during the previous 5 years.
• 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.
• Renal insufficiency
• Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study.
• Diseases with a contraindication for the use of adrenaline (e.g. hyperthyroidism, glaucoma).
• Use of systemic steroids within 4 weeks before start of the study and during the study.
• Treatment with systemic and local β-blockers.
• Known allergy towards constituents of the vaccine
• Alcohol, drug or medication abuse within the past year.

Sponsors & Collaborators

• Odense University Hospital: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Biomay AG: collaborator
• European Commission: collaborator
• University of Salzburg: collaborator

Study Sites (1)

Odense Research Center for Anaphylaxis, Odense University Hospital

Odense, 5000, Denmark

Location

Study Officials

• Carsten Bindslev-Jensen, Professor

  Odense research Center for Anaphylaxis, Odense University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A randomized, double-blind, placebo-controlled, single centre Phase I study with an open comparator group

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 3, 2021
• Study Start: September 17, 2018
• Primary Completion: March 22, 2019
• Study Completion: March 22, 2019
• Last Updated: December 11, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)