Clinical trial NCT01438463: PURETHAL® Mites Dose Range Finding Study in Patients With Persistent Allergic Rhinitis/Rhinoconjunctivitis
Official title: A Multi-centre, Randomized, Double-blind, Placebo-controlled, Dose Range Finding Study to Identify the Optimal Dose of PURETHAL® Mites SCIT in Patients With House Dust Mites-induced Persistent Allergic Rhinitis/Rhinoconjunctivitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinitis
Allergic Rhinoconjunctivitis
Keywords: non-seasonal allergy
house dust mite
immunotherapy
dose response
Lead sponsor: HAL Allergy
Sponsor class: INDUSTRY
First posted: 2011-09-22
Enrollment: 290
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 objective of the present study is to characterize the dose-response relationship of PURETHAL® Mites with a nasal provocation test in order to support the optimal dose in terms of clinical efficacy and safety.

For this purpose 5 groups of 50 patients, suffering from rhinitis or rhinoconjunctivitis due to House Dust Mite Allergy will be treated during 1 year. Before start, after 6 months of treatment and at the end of the study patients will be subjected to a nasal provocation test.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Patients (male or female) must be ≥ 18 and ≤ 60 years at screening
* Patients with allergic rhinitis or rhinoconjunctivitis for at least 1 year; allergic symptoms related to HDM, with or without concomitant clinically stable controlled mild to moderate asthma (according to GINA classification)
* Patients with a history of concomitant asthma should have a FEV1 \> 70% at inclusion. Patients without a history of asthma should have a FEV1 \> 70% or a PEF \> 80%.
* Positive SPT to HDM D. pter and/or D. far
* Serum specific IgE-test (ssIgE) level for HDM D. pter or D. far at screening
* Positive nasal provocation test for HDM extract at screening

Exclusion Criteria:

* Current clinically relevant symptoms of seasonal rhinitis/rhinoconjunctivitis caused by other allergen(s) than HDM (with a demonstrated positive SPT for this allergen) at the time of inclusion
* Patients sensitized to animals should not be included if they are symptomatic upon exposure and regularly exposed to animals
* Completed allergen-specific immunotherapy (SCIT or SLIT) with HDM within the last 5 years
* Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the past 5 years
* Allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period
* Any vaccination one week before start of therapy and during the up-dosing phase
* Any anti-IgE therapy within the last 6 months prior to inclusion and during study
* Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
* Active malignancies or any malignant disease in the past 5 years
* A chronic or acute disease that in the opinion of the investigator might place the patient at an additional risk, 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
* Moderate to severe nasal obstructive diseases such as polyps, septal deviations etc.
* Clinically significant chronic sinusitis or ocular infection
* Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma)
* Use of systemic corticosteroids within 4 weeks of screening
* Treatment with systemic or local b-blockers
* Participation in a clinical study with a new investigational drug within the last 3 months or a biological within the last 6 months prior to the study or during the study
* Pregnancy, lactation or inadequate contraceptive measures (contraceptive measures considered as adequate include appropriate use of oral contraception, i.m. contraception or a contraceptive device)
* Alcohol, drug, or medication abuse within the past year and during study
* Any abnormal laboratory parameter at screening that in the opinion of the investigator is considered clinically relevant
* Lack of co-operation or compliance
* Severe psychiatric, psychological, or neurological disorders
* Patients who are employees of the department, 1st grade relatives, or partners of the investigator
* Expected changes in HDM exposure during the study (avoidance measures, move, etc.)

Primary outcomes:
measure: Sensitivity to House Dust Mite (HDM) allergen assessed by a Nasal Provocation Test
timeFrame: 12 months
Secondary outcomes:
measure: Sensitivity to HDM allergen assessed by a Nasal Provocation Test
timeFrame: 6 months
measure: Average Adjusted daily Symptom Score (AAdSS)
timeFrame: last 2 months of treatment
measure: Peak Nasal Inspiratory Flow (PNIF)
timeFrame: at each visit during 1 year treatment
measure: Specific serum IgE, IgG, and IgG4 immunoglobulin concentrations to house dust mite
timeFrame: 6 and 12 months treatment
measure: Local and systemic reactions after injection as a measure of Safety and Tolerability
timeFrame: 24 hours after each injection during 1 year treatment
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Univ.-Klinik für Dermatologie und Venerologie
city: Innsbruck
country: Austria
facility: Universitätsklinik für Hals -, Nasen - und Ohrenheilkunde
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven campus Sint Rafaël
city: Liège
country: Belgium
facility: CHU de Liège
city: Berlin
country: Germany
facility: HNO-Praxis Dr. Hippke
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Chemnitz
country: Germany
facility: HNO-Praxis
city: Dortmund
country: Germany
facility: Gemeinschaftspraxis Pneumologie und Allergologie Dr. Hans-Christian Blum
city: Duisburg
country: Germany
facility: HNO-Praxis Dr. U. Thieme
city: Düren
country: Germany
facility: Medizinisches Versorgungszentrum
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Göttingen
country: Germany
facility: HNO Gemeinschaftspraxis
city: Hannover
country: Germany
facility: Pneumologische Praxis Hannover Nordstadt
city: Heidelberg
country: Germany
facility: HNO Gemeinschaftspraxis
city: Jülich
country: Germany
facility: HNO-Praxis
city: Leipzig
country: Germany
facility: POIS Leipzig GbR
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
city: Mönchengladbach
country: Germany
facility: CRS Clinical Research Services Möchengladbach GmbH
city: München
country: Germany
facility: Gemeinschaftspraxis HNO/Allergologie
city: München
country: Germany
facility: Klinikum der Universität München
city: München
country: Germany
facility: Pneumologie Odeonsplatz
city: Pirna
country: Germany
facility: HNO-Praxis
city: Schorndorf
country: Germany
facility: Praxisgemeinschaft Reiber & Partner
city: Stuttgart
country: Germany
facility: Universitätsklinikum Stuttgart
city: Stuttgart
country: Germany
facility: Hautarztpraxis
city: Wiesbaden
country: Germany
facility: Zentrum für Rhinologie und Allergologie
city: Almere
country: Netherlands
facility: EB FlevoResearch
city: Arnhem
country: Netherlands
facility: Allergologie Praktijk Arnhem (APA)
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer (Amstelwijck)
city: Groningen
country: Netherlands
facility: QPS Onderzoekskliniek Universitair Medisch Centrum Groningen
city: Tilburg
country: Netherlands
facility: St. Elisabethziekenhuis
city: Barcelona
country: Spain
facility: Hospital Clinico Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Germans Trios i Pujol
city: Valencia
country: Spain
facility: Hospital Universitari Politecnic La Fe
Study officials:
affiliation: University Gent, Belgium
name: Claus Bachert, PhD, MD
role: STUDY_CHAIR
References: