Clinical trial NCT02231307: SUBLIVAC FIX Birch Phase III Short-term Efficacy
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Clinical Efficacy and Safety of SUBLIVAC FIX Birch Immunotherapy in Patients Suffering From Allergic Rhinitis/Rhinoconjunctivitis Caused by Birch Pollen.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Birch Pollen Induced Rhinitis/Rhinoconjunctivitis
Keywords: sublingual immunotherapy
birch pollen
allergic rhinitis / rhinoconjunctivitis
efficacy
Lead sponsor: HAL Allergy
Sponsor class: INDUSTRY
First posted: 2014-09-04
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this phase III study is to asses if SUBLIVAC FIX Birch is safe and effective in reducing birch allergy induced symptoms and birch allergy medication usage.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Age ≥ 18 and ≤65 years
* Moderate-to-severe birch pollen induced allergic rhinitis/rhinoconjunctivitis based on ARIA classification for at least 2 consecutive years
* FEV1 (forced expiratory volume at one second) \> 70% (of predicted value) for patients with a history of asthma, FEV1 \> 70% or PEF (peak expiratory flow) \> 80% (of predicted value) for patients without a history of asthma
* Positive SPT (skin prick test) for birch pollen (mean wheal diameter ≥ 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter ≥ 3mm)) assessed during screening.
* Serum specific anti-birch IgE (immunoglobulin E) concentration \>0.7 U/ml
* Patients should be willing and capable to complete an e-diary daily during the birch pollen season (≥ 60% compliance in completion between Visit 1 and 2).
* A positive Nasal Provocation Test to birch pollen at Visit 2 (Lebel score ≥ 6) or a documented positive test within 1 year before start of treatment

Exclusion Criteria:

* Patients sensitized and symptomatic to pets should not be included if they are regularly exposed to pets
* Specific immunotherapy (SCIT or SLIT) with birch pollen or a cross-reacting allergen within the last 5 years
* SPT positive (mean wheal diameter ≥ 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter ≥ 3mm)) patients to allergen(s) other than birch pollen, in the absence of a negative provocation test for this allergen(s) (within 1 year), who are expected to have clinically relevant symptoms during the birch pollen season
* Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the last 5 years
* (Ongoing) allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) during the study period
* Vaccination one week before start of treatment and/or during the up-dosing phase
* Treatment with experimental products within the last 3 months or biologicals (including anti-IgE or TNF (tumor necrosis factor) - α treatment) within the last 6 months or during the study
* Uncontrolled asthma or other active respiratory diseases
* Clinically significant chronic sinusitis, ocular infection or severe inflammation of the oral mucosa
* Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
* Active malignancies or any malignant disease in the last 5 years
* Acute or chronic disease that in the opinion of the investigator is an additional risk for the patients, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, or haematological disorders
* Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma)
* Use of systemic corticosteroids 4 weeks before the study
* Treatment with systemic or local β-blockers
* Known hypersensitivity to any of the excipients (Disodium phosphate dihydrate, Sodium dihydrogen phosphate dehydrate, aminocaproic acid, Peppermint oil, Caramel Colorant or Glycerol)
* A positive urine pregnancy test, lactation or inadequate contraceptive methods (adequate methods: oral contraceptives, IUD (intrauterine device), condom use and having no sexual relationship with a man)
* Alcohol-, drug or medication abuse
* Lack of co-operation or compliance
* Severe psychiatric, psychological, or neurological disorders
* Any physical or mental condition that precludes administration or allergen-specific immunotherapy, compliance or participation in a clinical trial
* Patients who are employees of the department, 1st grade relatives, or partners of the investigator
* Patients who have planned holidays outside the country for more than 7 continuous days during the defined pollen season (1st of March till 31st of May)

Primary outcomes:
measure: combined symptom medication score
timeFrame: 3 months
Secondary outcomes:
measure: symptom score
timeFrame: 3 months
measure: Quality of Life questionnaires
timeFrame: 3 months
measure: Serum specific immunoglobulin levels
timeFrame: up to 9 months
measure: local and systemic reactions
timeFrame: up to 9 months
measure: (serious) adverse events
timeFrame: up to 9 months
measure: blood safety parameters
timeFrame: up to 9 months
measure: urinalysis
timeFrame: up to 9 months
measure: medication score
timeFrame: up to 3 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques universitaire St. Luc
city: Gent
country: Belgium
facility: University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: CHR Citadelle
city: Liege
country: Belgium
facility: CHU de Liege
city: Breclav
country: Czech Republic
facility: Alergologicka ambulance
city: Brno
country: Czech Republic
facility: AKI spol. s.r.o.
city: Liberec
country: Czech Republic
facility: Alergologicka ambulance
city: Most
country: Czech Republic
facility: Ordinace Alergologie
city: Plzen
country: Czech Republic
facility: Respiral s.r.o.
city: Plzen
country: Czech Republic
facility: Ustav imunologie a alergologie
city: Tabor
country: Czech Republic
facility: Kasmed s.r.o.
city: Bamberg
country: Germany
facility: CIMS Studienzentrum Bamberg
city: Berlin
country: Germany
facility: Charite Universitatsmedizin
city: Hamburg
country: Germany
facility: Dermatologikum Hamburg
city: Heidelberg
country: Germany
facility: HNO Gemeinschaftspraxis
city: Hildesheim
country: Germany
facility: Hautarztpraxis fur Dermatologie & asthetische medizin
city: Leipzig
country: Germany
facility: Praxis fur Atemwegserkrankungen
city: Saalfeld/Saale
country: Germany
facility: FA HNOW Allergologie
city: Schwabach
country: Germany
facility: Praxis Dr. Jager
city: Stuttgart
country: Germany
facility: Klinik fur Dermatologie & Allergologie
city: Wiesbaden
country: Germany
facility: HNO Wiesbaden Institute for Allergology and Rhinology
city: Bialystok
country: Poland
facility: Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny
city: Bielsko-Biala
country: Poland
facility: NZOZ ZLS Medex Sp. z o.o. Poradnia Alergologiczna
city: Bienkowka
country: Poland
facility: SP-ZOZ Osrodek Zdrowia w Bienkowce
city: Gdansk
country: Poland
facility: NZOZ Clinica Vitae
city: Krakow
country: Poland
facility: Grazyna Pulka Specjalistyczny Osrodek 'All-Med'
city: Lodz
country: Poland
facility: NZOZ Centrum Alergologii Krzysztof Buczylko
city: Lodz
country: Poland
facility: Poradnia Alergologii i Chorob Pluc Uniwersytecki Szpital Kliniczny
city: Lublin
country: Poland
facility: NZOZ Centrum Alergologii
city: Lublin
country: Poland
facility: Przychodnia Alergologiczno-Pulmonologiczna ALERGOPNEUMA
city: Poznan
country: Poland
facility: Centrum Alergologii Teresa Hofman
city: Strzelce Opolskie
country: Poland
facility: Centrumk Medyczne Lucyna i Andrzej Dymek
city: Tarnow
country: Poland
facility: ALERGOMED Specjalistyczna Przychodnia Lekarska
city: Wroclaw
country: Poland
facility: EMC Intytut Medyczny S.A. Przychodnia przy Lowieckiej
city: Bardejov
country: Slovakia
facility: ALIAN s.r.o. Ambulancia alergologie a klinickej imunologie
city: Kosice
country: Slovakia
facility: Alerso s.r.o. Imunoalergologicka ambulancie
city: Kosice
country: Slovakia
facility: STALERG s.r.o. Imunoalergologicka ambulancia
city: Levice
country: Slovakia
facility: DANIMED, spol. s.r.o. Ambulancia klinkckej imunologie a alergologie
city: Presov
country: Slovakia
facility: EMED s.r.o. Alergoimunologicke centrum
Study officials:
affiliation: Zentrum für Rhinologie und Allergologie, An-den-Quellen-10, 65189 Wiesbaden, Germany
name: Oliver Pfaar, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fortescue R, Kew KM, Leung MST. Sublingual immunotherapy for asthma. Cochrane Database Syst Rev. 2020 Sep 14;9(9):CD011293. doi: 10.1002/14651858.CD011293.pub3.
citation: Pfaar O, Bachert C, Kuna P, Panzner P, Dzupinova M, Klimek L, van Nimwegen MJ, Boot JD, Yu D, Opstelten DJE, de Kam PJ. Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma. J Allergy Clin Immunol. 2019 Mar;143(3):970-977. doi: 10.1016/j.jaci.2018.11.018. Epub 2018 Nov 30.