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

Allergic Rhinitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01731249
• Other study ID #: VO68.10
• Secondary ID: 2010-020693-42
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2012
• Last updated: November 22, 2012
• Start date: November 2010
• Est. completion date: October 2012

Study information

• Verified date: November 2012
• Source: Stallergenes
• Contact: n/a
• Is FDA regulated: No
• Health authority: Czech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyEstonia: The State Agency of MedicineFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthPoland: Ministry of HealthSlovakia: State Institute for Drug ControlSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 574
• Est. completion date: October 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allergic Conjunctivitis
• Allergic Rhinitis
• Conjunctivitis
• Conjunctivitis, Allergic
• Hypersensitivity
• Rhinitis, Allergic, Seasonal
• Seasonal Allergy

Intervention

Biological:
• Placebo
10 actuations of placebo sublingual solution once daily 5 months a year and during 2 years
• Birch pollen allergen extract
Sublingual solution of Birch pollen allergen extract 300IR (10 actuations) once daily 5 months per year and during 2 years

Locations

Country	Name	City	State
Czech Republic	Alergologicka ordinace	Plzen
Denmark	National University Hospital - Allergy Unit 4222	Copenhagen
Estonia	Merekivi Perearstid OÜ	Tallinn
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
France	NHC, Hôpitaux Universitaires de Strasbourg	Strasbourg
Germany	Universitätsmedizin Berlin - Allergie-Centrum-Charité	Berlin
Latvia	Centre of Investigations and Treatment of Allergic Diseases	Riga
Lithuania	Allergic Diseases Diagnostics and Treatment Centre	Vilnius
Poland	SPZOZ Uniwersytecki Szpital Kliniczny Nr 1im.N.Barlickiego w Uniwersystetu Medycznego w Lodzi	Lodz
Slovakia	Imunologicko-alergologicka amb.	Banska Bystrica
Sweden	Sahlgrenska Universitetssjukhuset - Avd för Lungmedicin och Allergi	Göteborg

Sponsors (5)

Lead Sponsor	Collaborator
Stallergenes	Aptuit Inc., Cenduit LLC, PHT Corporation, Quintiles, Inc.

Countries where clinical trial is conducted

Czech Republic,  Denmark,  Estonia,  Finland,  France,  Germany,  Latvia,  Lithuania,  Poland,  Slovakia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average Adjusted Symptom Score	Symptom score adjusted on patient's rescue medication usage	Year 2 of treatment	No
Secondary	Average Rhinoconjunctivitis Total Symptom Score		Year 2 of treatment	No
Secondary	Average Rescue Medication Score		Year 2 of treatment	No
Secondary	Each of Six Individual Average Rhinoconjunctivitis Symptom Scores		Year 2 of treatment	No
Secondary	Average Combined Score		Year 2 of treatment	No
Secondary	Average Rhinoconjunctivitis Visual Analogue Scale Score		Year 2 of treatment	No
Secondary	Average Adjusted Visual Analogue Scale Score		Year 2 of treatment	No
Secondary	Rescue Medication Usage		Year 2 of treatment	No
Secondary	Proportion of Symptom-controlled Days		Year 2 of treatment	No
Secondary	Rhinoconjunctivitis Quality of Life Questionnaire		Year 2 of treatment	No
Secondary	Global evaluation of the efficacy by the patient		Year 2 of treatment	No
Secondary	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)	No
Secondary	Asthma		Before, during and after each pollen season (over 2 years)	No
Secondary	Immunological markers specific for birch pollen		Before and after each treatment period (over 2 years)	No
Secondary	Economical Evaluation	Proportion of days-off due to birch pollen-induced symptoms	Year 2 of treatment	No
Secondary	Wheal diameter of the birch allergen Skin prick test		Before and after each treatment period (over 2 years)	No
Secondary	Oral Provocation Test	Analysis on a subset of patients presenting an Oral Allergy Syndrome at study entry	Year 2 of treatment	No
Secondary	Mucosa Local Inflammation	Analysis on a subset of patients	Year 1 of treatment	No
Secondary	Safety assessments	adverse events, physical examination including vital signs and laboratory data described by number of patients in each treatment group	~20 months	Yes
Secondary	Average adjusted Symptom score analysis by tertiles		Year 2 of treatment	No