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

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

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.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinitis; Allergic Rhinoconjunctivitis
• Intervention / Treatment: Biological: Placebo; Biological: PURETHAL Mites 6,667 AU/ml; Biological: PURETHAL Mites 20,000 AU/ml; Biological: PURETHAL Mites 50,000 AU/ml; Biological: PURETHAL Mites 100,000 AU/ml

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A-6020
    • Univ.-Klinik für Dermatologie und Venerologie
  • Innsbruck, Austria, A-6020
    • Universitätsklinik für Hals -, Nasen - und Ohrenheilkunde
• Belgium
  • Gent, Belgium, B-9000
    • UZ Gent
  • Leuven, Belgium, B-3000
    • UZ Leuven campus Sint Rafaël
  • Liège, Belgium, B-4000
    • CHU de Liège
• Germany
  • Berlin, Germany, D-13057
    • HNO-Praxis Dr. Hippke
  • Bonn, Germany, D-53127
    • Universitätsklinikum Bonn
  • Chemnitz, Germany, D-09130
    • HNO-Praxis
  • Dortmund, Germany, D-44263
    • Gemeinschaftspraxis Pneumologie und Allergologie Dr. Hans-Christian Blum
  • Duisburg, Germany, D-47051
    • HNO-Praxis Dr. U. Thieme
  • Düren, Germany, D-52351
    • Medizinisches Versorgungszentrum
  • Erlangen, Germany, D-91052
    • Universitatsklinikum Erlangen
  • Göttingen, Germany, D-37073
    • HNO Gemeinschaftspraxis
  • Hannover, Germany, D-30167
    • Pneumologische Praxis Hannover Nordstadt
  • Heidelberg, Germany, D-69126
    • HNO Gemeinschaftspraxis
  • Jülich, Germany, D-52428
    • HNO-Praxis
  • Leipzig, Germany, D-04357
    • POIS Leipzig GbR
  • Mannheim, Germany, D-68167
    • CRS Clinical Research Services Mannheim GmbH
  • Mönchengladbach, Germany, D-41061
    • CRS Clinical Research Services Möchengladbach GmbH
  • München, Germany, D-80331
    • Gemeinschaftspraxis HNO/Allergologie
  • München, Germany, D-80337
    • Klinikum der Universität München
  • München, Germany, D-80539
    • Pneumologie Odeonsplatz
  • Pirna, Germany, D-01796
    • HNO-Praxis
  • Schorndorf, Germany, D-73614
    • Praxisgemeinschaft Reiber & Partner
  • Stuttgart, Germany, D-70374
    • Universitätsklinikum Stuttgart
  • Stuttgart, Germany, D-70499
    • Hautarztpraxis
  • Wiesbaden, Germany, D-65183
    • Zentrum für Rhinologie und Allergologie
• Netherlands
  • Almere, Netherlands, NL-1311 RL
    • EB FlevoResearch
  • Arnhem, Netherlands, NL-6824 BJ
    • Allergologie Praktijk Arnhem (APA)
  • Dordrecht, Netherlands, NL-3317 NM
    • Albert Schweitzer (Amstelwijck)
  • Groningen, Netherlands, NL-9713 GZ
    • QPS Onderzoekskliniek Universitair Medisch Centrum Groningen
  • Tilburg, Netherlands, NL-5022 GC
    • St. Elisabethziekenhuis
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinico Barcelona
  • Barcelona, Spain, 08916
    • Hospital Universitario Germans Trios i Pujol
  • Valencia, Spain, 46026
    • Hospital Universitari Politecnic La Fe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	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.
Experimental: PURETHAL Mites, 6,667 AU/ml	Biological: 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.
Experimental: PURETHAL Mites, 20,000 AU/ml	Biological: 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.
Experimental: PURETHAL Mites, 50,000 AU/ml	Biological: 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.
Experimental: PURETHAL Mites, 100,000 AU/ml	Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sensitivity to House Dust Mite (HDM) allergen assessed by a Nasal Provocation Test	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Sensitivity to HDM allergen assessed by a Nasal Provocation Test	6 months
Average Adjusted daily Symptom Score (AAdSS)	last 2 months of treatment
Peak Nasal Inspiratory Flow (PNIF)	at each visit during 1 year treatment
Specific serum IgE, IgG, and IgG4 immunoglobulin concentrations to house dust mite	6 and 12 months treatment
Local and systemic reactions after injection as a measure of Safety and Tolerability	24 hours after each injection during 1 year treatment

Collaborators and Investigators

• Sponsor: HAL Allergy
• Investigators: Study Chair: Claus Bachert, PhD, MD, University Gent, Belgium

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 22, 2011

Study Record Updates

• Last Update Posted (Estimate): May 29, 2013
• Last Update Submitted That Met QC Criteria: May 28, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: immunotherapy; house dust mite; non-seasonal allergy; dose response
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Conjunctival Diseases; Rhinitis; Rhinitis, Allergic; Conjunctivitis
• Other Study ID Numbers: PM/0037