Clinical trial NCT01639768: SUBLIVAC FIX Birch Dose Tolerability/Dose Range Finding
Official title: A Randomized, Double-blind, Placebo-controlled Study to Determine Safety, Tolerability and the Optimal Effective Dose of SUBLIVAC FIX Birch in Patients With Allergic Rhinitis/Rhinoconjunctivitis Caused by Birch Pollen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinitis
Allergic Rhinoconjunctivitis
Keywords: Sublingual immunotherapy
Dose range finding
Dose tolerability
Birch pollen
Allergic rhinitis/rhinoconjunctivitis
Safety
Immunogenicity
Lead sponsor: HAL Allergy
Sponsor class: INDUSTRY
First posted: 2012-07-13
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to determine the optimal effective dose of SUBLIVAC FIX Birch based on reduction of upper airways reactivity after 5 months of treatment with different dosages of SUBLIVAC FIX Birch compared to placebo. Furthermore, safety and tolerability will be assessed by the number of related Adverse Events of different dosages of SUBLIVAC FIX Birch compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Age ≥ 18 ≤ 60 years
* Allergic rhinitis/rhinoconjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma
* FEV1 \> 70% for patients with a history of asthma, FEV \> 70% or PEF \> 80% for patients without a history of asthma
* 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.
* Positive serum specific anti-birch IgE-test (\> 0.7 U/mL)
* A positive TNPT for birch pollen at screening (Lebel score ≥ 6) at

  * 10,000 AU/mL

Exclusion Criteria:

* Patients with (expected) clinically relevant symptoms during the course of the trial due to concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3mm) to allergens other than birch pollen
* Patients sensitized to pets should not be included if they are regularly exposed to pets and are symptomatic upon exposure to pets
* Completed immunotherapy (SCIT or SLIT) with birch pollen allergens within the past 5 years
* Completed unsuccessful specific immunotherapy in the past
* Vaccination within one week before start of therapy or during the initiation phase
* Anti-IgE therapy within the 6 months prior to inclusion and during the study
* Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
* 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
* Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
* Moderate to severe nasal obstructive diseases that preclude a TNPT (septal deviation, nasal polyps, recent nasal surgery, etc.)
* 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
* Participation in a clinical study with a new investigational drug within the last 3 months or for a biological within the last 6 months prior to or during the study
* Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or -pill)
* Alcohol, drug or medication abuse within the past year
* Any clinically significant abnormal laboratory parameter at screening
* Lack of cooperation or compliance
* Severe psychiatric, psychological, or neurological disorders
* Patients who are employees of the institution or 1st grade relatives or partners of the investigator

Primary outcomes:
measure: Nasal Provocation Test (NPT)
timeFrame: 5 months
measure: Number of related AEs
timeFrame: First ten days of study medication intake
Secondary outcomes:
measure: Serum specific immunoglobulin levels (IgE, IgG, IgG4)
timeFrame: 5 months
measure: Number of local and systemic reactions
timeFrame: Duration of study medication intake (approximately 5 months)
measure: Peak Nasal Inspiratory Flow (PNIF)
timeFrame: 5 months
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: AKI, spol s. r.o.
city: Most
country: Czech Republic
facility: Ordinace Alergologie
city: Plzeň
country: Czech Republic
facility: Respiral s. r.o.
city: Plzeň
country: Czech Republic
facility: Ústav imunologie a alergologie
city: Tábor
country: Czech Republic
facility: Kasmed s. r.o.
city: Leipzig
country: Germany
facility: Praxis für Atemwegserkrankungen
state: Sachsen
city: Dresden
country: Germany
facility: Medizinische Fakultät. Klinik und Poliklinik für HNO-Klinik
city: Wiesbaden
country: Germany
facility: HNO-Wiesbaden - Center for Rhinology and Allergology
city: Białystok
country: Poland
facility: Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny
city: Cieszyn
country: Poland
facility: NZOS "Zdrowie"
city: Katowice
country: Poland
facility: Poradnia Alergologiczna Samodzielnego Publicznego Szpitala Nr 5 Slaskiego Uniwersytetu Medycznego w Katowicach
city: Kraków
country: Poland
facility: Specjalistyczny Ośrodek Alergologiczno-Internistyczny "ALL-MED"
city: Lodz
country: Poland
facility: Poradnia Alergologii i Chorób Płuc SP ZOZ Uniwersytecki Szpital Kliniczny Nr.1 im. Norberta Barlickiego w Łodzi
city: Lublin
country: Poland
facility: ALERGOPNEUMA Marek Michnar i Wspolnicy Sp. Jawna
city: Lublin
country: Poland
facility: NZOZ Centrum Alergologii
city: Poznań
country: Poland
facility: Centrum Alergologii Teresa Hofman
city: Tarnów
country: Poland
facility: ALERGOMED Specjalistyczna Przychodnia Lekarska Sp. z o.o.
city: Wrocław
country: Poland
facility: EMC Intytut Medyczny S.A. Przychodnia przy Łowieckiej
city: Wrocław
country: Poland
facility: NZOZ Lekarze Specjaliści J. Małolepszy i Partnerzy
city: Łódź
country: Poland
facility: NZOZ Centrum Alergologii
Study officials:
affiliation: Zentrum für Rhinologie und Allergologie, An-den-Quellen-10, 65189 Wiesbaden, Germany
name: Oliver Pfaar, PD. Dr. med.
role: STUDY_CHAIR
References:
citation: Pfaar O, van Twuijver E, Boot JD, Opstelten DJ, Klimek L, van Ree R, Diamant Z, Kuna P, Panzner P. A randomized DBPC trial to determine the optimal effective and safe dose of a SLIT-birch pollen extract for the treatment of allergic rhinitis: results of a phase II study. Allergy. 2016 Jan;71(1):99-107. doi: 10.1111/all.12760. Epub 2015 Oct 26.