Efficacy and Safety Study of a Sublingual Immunotherapy Solution to Treat Patients Suffering From Birch Pollen Allergic Rhinoconjunctivitis

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

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.

Study Overview

• Status: Completed
• Conditions: Hypersensitivity; Allergic Rhinitis; Allergic Conjunctivitis; Seasonal Allergy
• Intervention / Treatment: Biological: Placebo; Biological: Birch pollen allergen extract

• Study Type: Interventional
• Enrollment (Actual): 574
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czech Republic
  • Plzen, Czech Republic, 30100
    • Alergologicka ordinace
• Denmark
  • Copenhagen, Denmark, 2100
    • National University Hospital - Allergy Unit 4222
• Estonia
  • Tallinn, Estonia, 10617
    • Merekivi Perearstid OU
• Finland
  • Helsinki, Finland, 00029
    • Helsingin yliopistollinen keskussairaala
• France
  • Strasbourg, France, 67091
    • NHC, Hôpitaux Universitaires de Strasbourg
• Germany
  • Berlin, Germany, 10117
    • Universitätsmedizin Berlin - Allergie-Centrum-Charité
• Latvia
  • Riga, Latvia, 1003
    • Centre of Investigations and Treatment of Allergic Diseases
• Lithuania
  • Vilnius, Lithuania, 08109
    • Allergic Diseases Diagnostics and Treatment Centre
• Poland
  • Lodz, Poland, 90-153
    • SPZOZ Uniwersytecki Szpital Kliniczny Nr 1im.N.Barlickiego w Uniwersystetu Medycznego w Łodzi
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Imunologicko-alergologicka amb.
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Universitetssjukhuset - Avd för Lungmedicin och Allergi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo sublingual solution	Biological: Placebo; 10 actuations of placebo sublingual solution once daily 5 months a year and during 2 years
Experimental: Birch pollen allergen extract; Sublingual Solution of Birch pollen allergen extract 300IR once daily 5 months per year and during 2 years	Biological: Birch pollen allergen extract; Sublingual solution of Birch pollen allergen extract 300IR (10 actuations) once daily 5 months per year and during 2 years; Other Names: Staloral Birch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Adjusted Symptom Score	Symptom score adjusted on patient's rescue medication usage	Year 2 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Rhinoconjunctivitis Total Symptom Score		Year 2 of treatment
Average Rescue Medication Score		Year 2 of treatment
Each of Six Individual Average Rhinoconjunctivitis Symptom Scores		Year 2 of treatment
Average Combined Score		Year 2 of treatment
Average Rhinoconjunctivitis Visual Analogue Scale Score		Year 2 of treatment
Average Adjusted Visual Analogue Scale Score		Year 2 of treatment
Rescue Medication Usage		Year 2 of treatment
Proportion of Symptom-controlled Days		Year 2 of treatment
Rhinoconjunctivitis Quality of Life Questionnaire		Year 2 of treatment
Global evaluation of the efficacy by the patient		Year 2 of treatment
Sensitization profile	sensitization profile (mono- vs poly-sensitized) is derived from the skin prick test results	Before and after each treatment period (over 2 years)
Asthma		Before, during and after each pollen season (over 2 years)
Immunological markers specific for birch pollen		Before and after each treatment period (over 2 years)
Economical Evaluation	Proportion of days-off due to birch pollen-induced symptoms	Year 2 of treatment
Wheal diameter of the birch allergen Skin prick test		Before and after each treatment period (over 2 years)
Oral Provocation Test	Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry	Year 2 of treatment
Mucosa Local Inflammation	Analysis on a subset of patients	Year 1 of treatment
Safety assessments	adverse events, physical examination including vital signs and laboratory data described by number of patients in each treatment group	~20 months
Average adjusted Symptom score analysis by tertiles		Year 2 of treatment

Collaborators and Investigators

• Sponsor: Stallergenes Greer
• Collaborators: Quintiles, Inc.; Cenduit LLC; Aptuit Inc.; PHT Corporation
• Investigators: Principal Investigator: Margitta WORM, MD, PR, Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie, Charité Campus Mitte, Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: November 15, 2012
• First Submitted That Met QC Criteria: November 15, 2012
• First Posted (Estimate): November 21, 2012

Study Record Updates

• Last Update Posted (Estimate): November 27, 2012
• Last Update Submitted That Met QC Criteria: November 22, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Sublingual immunotherapy; Allergic rhinoconjunctivitis; Birch pollen extract solution
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Nose Diseases; Conjunctival Diseases; Hypersensitivity; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Conjunctivitis; Conjunctivitis, Allergic
• Other Study ID Numbers: VO68.10; 2010-020693-42 (EudraCT Number)