PURETHAL® Mites Dose Range Finding Study in Patients With Persistent Allergic Rhinitis/Rhinoconjunctivitis

Allergic Rhinitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01438463
• Other study ID #: PM/0037
• Status: Completed
• Phase: Phase 2
• First received: September 20, 2011
• Last updated: May 28, 2013
• Start date: September 2011
• Est. completion date: May 2013

Study information

• Verified date: May 2013
• Source: HAL Allergy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Paul-Ehrlich-InstitutNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 290
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.)

Study Design

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

Related Conditions & MeSH terms

• Allergic Rhinitis
• Allergic Rhinoconjunctivitis
• Conjunctivitis
• Conjunctivitis, Allergic
• Rhinitis

Intervention

Biological:
• Placebo
Increasing volumes of placebo, will be administered by subcutaneous injection (starting with 0.05 ml) at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of placebo, are given at 4-weekly intervals.
• PURETHAL Mites 6,667 AU/ml
Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.
• PURETHAL Mites 20,000 AU/ml
Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.
• PURETHAL Mites 50,000 AU/ml
Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.
• PURETHAL Mites 100,000 AU/ml
Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.

Locations

Country	Name	City	State
Austria	Univ.-Klinik für Dermatologie und Venerologie	Innsbruck
Austria	Universitätsklinik für Hals -, Nasen - und Ohrenheilkunde	Innsbruck
Belgium	UZ Gent	Gent
Belgium	UZ Leuven campus Sint Rafaël	Leuven
Belgium	CHU de Liège	Liège
Germany	HNO-Praxis Dr. Hippke	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	HNO-Praxis	Chemnitz
Germany	Gemeinschaftspraxis Pneumologie und Allergologie Dr. Hans-Christian Blum	Dortmund
Germany	HNO-Praxis Dr. U. Thieme	Duisburg
Germany	Medizinisches Versorgungszentrum	Düren
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	HNO Gemeinschaftspraxis	Göttingen
Germany	Pneumologische Praxis Hannover Nordstadt	Hannover
Germany	HNO Gemeinschaftspraxis	Heidelberg
Germany	HNO-Praxis	Jülich
Germany	POIS Leipzig GbR	Leipzig
Germany	CRS Clinical Research Services Mannheim GmbH	Mannheim
Germany	CRS Clinical Research Services Möchengladbach GmbH	Mönchengladbach
Germany	Gemeinschaftspraxis HNO/Allergologie	München
Germany	Klinikum der Universität München	München
Germany	Pneumologie Odeonsplatz	München
Germany	HNO-Praxis	Pirna
Germany	Praxisgemeinschaft Reiber & Partner	Schorndorf
Germany	Hautarztpraxis	Stuttgart
Germany	Universitätsklinikum Stuttgart	Stuttgart
Germany	Zentrum für Rhinologie und Allergologie	Wiesbaden
Netherlands	EB FlevoResearch	Almere
Netherlands	Allergologie Praktijk Arnhem (APA)	Arnhem
Netherlands	Albert Schweitzer (Amstelwijck)	Dordrecht
Netherlands	QPS Onderzoekskliniek Universitair Medisch Centrum Groningen	Groningen
Netherlands	St. Elisabethziekenhuis	Tilburg
Spain	Hospital Clinico Barcelona	Barcelona
Spain	Hospital Universitario Germans Trios i Pujol	Barcelona
Spain	Hospital Universitari Politecnic La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
HAL Allergy

Countries where clinical trial is conducted

Austria,  Belgium,  Germany,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity to House Dust Mite (HDM) allergen assessed by a Nasal Provocation Test		12 months	No
Secondary	Sensitivity to HDM allergen assessed by a Nasal Provocation Test		6 months	No
Secondary	Average Adjusted daily Symptom Score (AAdSS)		last 2 months of treatment	No
Secondary	Peak Nasal Inspiratory Flow (PNIF)		at each visit during 1 year treatment	No
Secondary	Specific serum IgE, IgG, and IgG4 immunoglobulin concentrations to house dust mite		6 and 12 months treatment	No
Secondary	Local and systemic reactions after injection as a measure of Safety and Tolerability		24 hours after each injection during 1 year treatment	Yes