Clinical trial NCT01731249: Efficacy and Safety Study of a Sublingual Immunotherapy Solution to Treat Patients Suffering From Birch Pollen Allergic Rhinoconjunctivitis
Official title: A Randomised, Double-blind, Placebo-controlled, Multi-national, Phase IIIb Study to Assess the Sustained Clinical Effect and Safety of Sublingual Immunotherapy Administered as Birch Pollen Extract Solution at a Dose of 300 IR Once Daily to Patients Suffering From Birch Pollen-induced Rhinoconjunctivitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypersensitivity
Allergic Rhinitis
Allergic Conjunctivitis
Seasonal Allergy
Keywords: Sublingual immunotherapy
Birch pollen extract solution
Allergic rhinoconjunctivitis
Lead sponsor: Stallergenes Greer
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
name: Aptuit
name: Cenduit LLC
name: PHT Corporation
First posted: 2012-11-21
Enrollment: 574
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 purpose of this 2-year study is to assess the sustained clinical efficacy and safety of 300 IR/day of a sublingual solution of birch pollen allergen extract starting 4 months prior to the birch pollen season and continuing over the birch pollen season compared with placebo for reduction of rhinoconjunctivitis-related symptoms and anti-allergy medication usage.


Eligibility criteria: Inclusion Criteria:

* Symptomatic birch pollen-related allergic rhinoconjunctivitis for at least the previous 2 pollen seasons requiring intake of symptomatic treatment.
* Sensitization to birch pollen demonstrated by a positive Skin Prick Test to birch pollen with wheal diameter \> 3 mm and birch pollen allergens specific IgE levels ≥ 0.70 kU/L.
* RRTSS based on the previous or on the penultimate birch pollen season ≥ 12 out of a maximum possible score of 18.
* Patients with an FEV1 (Forced Expiratory Volume at one second) ≥ 80% of the predicted value.
* Patients who are willing to comply with the protocol.
* Patients having given a signed informed consent before completing any study related procedure.

Exclusion Criteria:

* Patients with symptoms of rhinitis/rhinoconjunctivitis during the birch pollen season due to any other allergens (except alder and hazel). This includes patients with symptomatic allergic rhinitis/rhinoconjunctivitis due to cat or dog allergens, and living with these animals at home or at risk of frequent contacts with these animals (family, friends etc.) during the course of the study.
* Patient who previously received desensitization treatment to birch pollen and/or another Betulaceae sp. (for example hazel or alder) within the previous 5 years.
* Patients with ongoing treatment by immunotherapy with another allergen.
* Pregnancy (positive pregnancy test), breast-feeding.
* Female patients of childbearing potential planning a pregnancy during this study or not using a medically accepted contraceptive method (hormonal birth control \[orally, injectable or by implant, for at least 2 months before enrolment\], intrauterine device, spermicide used with a male condom, bilateral tubal ligation, diaphragm with spermicide, female condom, monogamous relationship with a vasectomised partner).
* Patients planning to move during the study or planning to leave the area during the birch pollen season for more than 1 week (7 consecutive days).
* Patients with moderate or severe persistent asthma (GINA 3 or 4).
* Patients with seasonal mild persistent asthma (GINA 2) necessitating treatment with inhaled glucocorticosteroids at a dose level greater than 400 mcg budesonide dose-equivalents.
* Patients with any nasal or oral condition that could interfere with the efficacy or safety assessments (such as nasal polyposis or oral inflammation).
* Patients with severe immune deficiency.
* Patients with a past or current disease, which as judged by the Investigator, may affect the patient's participation in or outcome of this study.
* Any other disease or condition which would place a patient at undue risk by being included in the study (according to the Investigator's opinion).
* Usual contra-indications of immunotherapy such as concomitant beta-blocker therapy whatever the route and/or immunosuppressive drugs.
* Patients treated with inhaled/systemic steroids (whatever the indication) within 4 weeks prior to Visit 1 (Screening), or with long acting systemic corticosteroids 12 weeks before Visit 1 (Screening).
* Patients under continuous corticotherapy (inhaled or systemic drugs).
* Patients following a strict low sodium diet as the study treatment contains 590 mg of sodium chloride per vial in a 10 mL solution.
* Investigators, co-Investigators, as well as their children or spouses and all study collaborators.

Primary outcomes:
measure: Average Adjusted Symptom Score
timeFrame: Year 2 of treatment
Secondary outcomes:
measure: Average Rhinoconjunctivitis Total Symptom Score
timeFrame: Year 2 of treatment
measure: Average Rescue Medication Score
timeFrame: Year 2 of treatment
measure: Each of Six Individual Average Rhinoconjunctivitis Symptom Scores
timeFrame: Year 2 of treatment
measure: Average Combined Score
timeFrame: Year 2 of treatment
measure: Average Rhinoconjunctivitis Visual Analogue Scale Score
timeFrame: Year 2 of treatment
measure: Average Adjusted Visual Analogue Scale Score
timeFrame: Year 2 of treatment
measure: Rescue Medication Usage
timeFrame: Year 2 of treatment
measure: Proportion of Symptom-controlled Days
timeFrame: Year 2 of treatment
measure: Rhinoconjunctivitis Quality of Life Questionnaire
timeFrame: Year 2 of treatment
measure: Global evaluation of the efficacy by the patient
timeFrame: Year 2 of treatment
measure: Sensitization profile
timeFrame: Before and after each treatment period (over 2 years)
measure: Asthma
timeFrame: Before, during and after each pollen season (over 2 years)
measure: Immunological markers specific for birch pollen
timeFrame: Before and after each treatment period (over 2 years)
measure: Economical Evaluation
timeFrame: Year 2 of treatment
measure: Wheal diameter of the birch allergen Skin prick test
timeFrame: Before and after each treatment period (over 2 years)
measure: Oral Provocation Test
timeFrame: Year 2 of treatment
measure: Mucosa Local Inflammation
timeFrame: Year 1 of treatment
measure: Safety assessments
timeFrame: ~20 months
measure: Average adjusted Symptom score analysis by tertiles
timeFrame: Year 2 of treatment
Other outcomes:
Locations:
city: Plzen
country: Czech Republic
facility: Alergologicka ordinace
city: Copenhagen
country: Denmark
facility: National University Hospital - Allergy Unit 4222
city: Tallinn
country: Estonia
facility: Merekivi Perearstid OÜ
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala
city: Strasbourg
country: France
facility: NHC, Hôpitaux Universitaires de Strasbourg
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin - Allergie-Centrum-Charité
city: Riga
country: Latvia
facility: Centre of Investigations and Treatment of Allergic Diseases
city: Vilnius
country: Lithuania
facility: Allergic Diseases Diagnostics and Treatment Centre
city: Lodz
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny Nr 1im.N.Barlickiego w Uniwersystetu Medycznego w Łodzi
city: Banska Bystrica
country: Slovakia
facility: Imunologicko-alergologicka amb.
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset - Avd för Lungmedicin och Allergi
Study officials:
affiliation: Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité Campus Mitte, Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany
name: Margitta WORM, MD, PR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Worm M, Rak S, de Blay F, Malling HJ, Melac M, Cadic V, Zeldin RK. Sustained efficacy and safety of a 300IR daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic rhinoconjunctivitis: results of a double-blind, placebo-controlled study. Clin Transl Allergy. 2014 Feb 11;4(1):7. doi: 10.1186/2045-7022-4-7.