ToleroMune House Dust Mites (HDM) Exposure Chamber Study

Study Overview
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Brief Summary
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House Dust Mites (HDM) are arachnids that infest bedding, carpet, upholstered furniture and fabric. Like many other allergens, exposure to HDM allergens in sensitised patients is associated with poorer lung function, greater medication requirements and more asthma symptoms as well as chronic rhinosinusitis symptoms. In contrast to other allergens, there is evidence that HDMA leads to the development of asthma, in addition to exacerbating pre-existing asthma in HDM-sensitised patients. ToleroMune HDM is a novel, synthetic, allergen-derived peptide desensitising vaccine, currently being developed for the treatment of HDM allergy This study will look at the efficacy, safety and tolerability of three doses of ToleroMune HDM in HDM allergic subjects following challenge with HDM allergen in an Environmental Exposure Chamber (EEC)).

Detailed Description
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This study is designed as a randomised, double-blind, placebo-controlled, parallel group study to evaluate the safety and tolerability of ToleroMune HDM in HDM allergic subjects with allergic rhinoconjunctivitis. The efficacy of ToleroMune Ragweed will be explored in subjects using an EEC. The study will consist of 3 study periods. In Period 1, Screening will be performed up to a maximum of 16 weeks before randomisation and may consist of one or two visits to the clinic, at the Investigator's discretion. Baseline Challenge will consist of 3 visits to the EEC. Eligible subjects will complete a daily diary card at home for two weeks following the final visit to the EEC. In Period 2, subjects in each cohort complying with the inclusion/exclusion criteria will be randomised to one of four groups and will receive treatment over 11 visits in 3 dosing periods for each subject. Within each dosing period visits will take place at intervals of 4 weeks (28±2 days). There will also be two EEC visits during the treatment period and one post treatment EEC visit. Following the final visit to the EEC, subjects will complete a daily diary card at home for two weeks. In Period 3, Follow-up will be conducted 16-21 days after the final EEC visit.

Official Title
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A Double-blind, Randomised, Placebo-controlled Study to Evaluate Three Doses of ToleroMune HDM in House Dust Mite Allergic Subjects Following Challenge With House Dust Mite Allergen in an Environmental Exposure Chamber.

Conditions
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Rhinoconjunctivitis

Intervention / Treatment
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* Biological: ToleroMune HDM
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Male or female, aged 18-65 years. Minimum 1-year documented history of rhinoconjunctivitis on exposure to HDM. Positive skin prick test to Der p allergen. Minimum qualifying rhinoconjunctivitis symptom scores Exclusion criteria History of asthma (asthma in childhood . A history of anaphylaxis to HDM allergen. Subjects with an FEV1 <80% of predicted. Subjects who cannot tolerate baseline challenge in the EEC. Subjects for whom administration of epinephrine is contra-indicated (e.g. subjects with acute or chronic symptomatic coronary heart disease or severe hypertension). A history of severe drug allergy, severe angioedema or anaphylactic reaction to food. A history of any significant disease or disorder (e.g. cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, neoplastic/malignant, psychiatric, major physical impairment).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Intradermal injection 1 x 11 administrations 4 weeks apart<br>|
| Experimental: ToleroMune HDM Dose 1<br> | Biological: ToleroMune HDM<br>* Intradermal injection 1 x 11 administrations 4 weeks apart<br>|
| Experimental: ToleroMune HDM Dose 2<br> | Biological: ToleroMune HDM<br>* Intradermal injection 1 x 11 administrations 4 weeks apart<br>|
| Experimental: ToleroMune HDM Dose 3<br> | Biological: ToleroMune HDM<br>* Intradermal injection 1 x 11 administrations 4 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Rhinoconjunctivitis Symptom Score |  | Up to 47 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom scores for nasal and non-nasal symptoms |  | Up to 47 weeks | 
| Total Rhinoconjunctivitis Symptom Score |  | Up to 19 weeks | 
| Total Rhinoconjunctivitis Symptom Score |  | Up to 36 weeks | 
| HDM specific IgA |  | Up to 53 weeks | 
| HDM specific IgE |  | Up to 53 weeks | 
| HDM specific IgG4 |  | Up to 53 weeks | 
| Adverse Events |  | Upto 53 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDM allergy, Rhinoconunctivitis, Environmental Exposure Chamber, Immunotherapy, ToleroMune HDM