Phase II HDM-SPIRE Safety and Efficacy Study

Study Overview
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Brief Summary
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The purpose of this study is to compare the treatment effect of three treatment regimens of HDM-SPIRE vs placebo and to evaluates the treatment effect of HDM-SPIRE on symptoms, rescue medication usage, Quality of Life and Sleep Quality

Official Title
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A Double-Blind, Randomised, Placebo-Controlled, Multi-Centre Field Study to Assess the Efficacy and Safety of HDM-SPIRE in Subjects With a History of House Dust Mite-Induced Rhinoconjunctivitis

Conditions
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Rhinoconjunctivitis

Intervention / Treatment
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* Drug: HDM-SPIRE
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18-65 years. Moderate to severe rhinoconjunctivitis on exposure to HDM for at least 1 years. Mean TRSS ≥10 Positive skin prick test to Der p and Der f. Dep p and Der f specific IgE ≥0.7 kU/L Exclusion Criteria: Diagnosis of asthma requiring Global Initiative for Asthma (GINA) Step 3 (www.ginasthma.org)or higher treatment FEV1 <80% of predicted. Clinically significant confounding symptoms of allergy to seasonal allergens during the final evaluation period. Significant symptoms of another clinically relevant illness that is likely to affect scoring of rhinoconjunctivitis symptoms. Clinically relevant abnormalities detected on physical examination. History of severe drug allergy, severe angioedema or anaphylactic reaction to food.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMD-SPIRE Treatment 1<br>4 x 12 nmol HDM-SPIRE followed by 4 x placebo 4 weeks apart | Drug: HDM-SPIRE<br>* 1 dose every 4 weeks<br>Drug: Placebo<br>* 1 dose every 4 weeks<br>|
| Experimental: HDM-SPIRE Treatment 2<br>4 x 12 nmol HDM-SPIRE 4 weeks apart followed by a second course of 4 x 12 nmol HDM-SPIRE 4 weeks apart | Drug: HDM-SPIRE<br>* 1 dose every 4 weeks<br>|
| Experimental: HDM-SPIRE Treatment 3<br>4 x 20 nmol HDM-SPIRE followed by 4 x placebo 4 weeks apart | Drug: HDM-SPIRE<br>* 1 dose every 4 weeks<br>Drug: Placebo<br>* 1 dose every 4 weeks<br>|
| Placebo Comparator: Placebo<br>8 x placebo 4 weeks apart | Drug: Placebo<br>* 1 dose every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Score of Symptoms and Allergy Medication | The primary endpoint was mean Combined Score (CS) over a 3 week period (50-52 weeks after randomisation) in the HDM-SPIRE treatment groups compared with the mean CS in the placebo group. A higher score indicated more severe symptoms or greater use of allergy rescue medication and thus a low score indicated a better outcome. CS = Total Rhinoconjunctivitis Symptom Score (TRSS) + Rescue Medication Score (RMS). Eight symptoms are defined in the TRSS, 4 nasal symptoms: runny nose, sneezing, blocked nose and itchy nose and 4 non-nasal symptoms: itchy eyes; watery eyes; red eyes, and sore eyes. Each symptom was rated in severity on a score of 0-3 (0=absent, 3=severe); TRSS was divided by the number of symptoms (8) to provide an average score per symptom of 0-3. The RMS score ranged from 0 (no allergy rescue medication use per day) to 3 (at least one dose of systemic corticosteroid per day). The RMS score was not additive, and therefore the maximum RMS was 3 and the maximum CS was 6. | Weeks 50 to 52 after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean RQLQ Score in HDM-SPIRE Treatment Groups Compared With Placebo | The RQLQ (Rhinoconjunctivitis Quality of Life Questionnaire) was completed by subjects at the end of the study (50-52 weeks after randomisation). RQLQ is a validated method of assessing quality of life and has 28 questions in seven domains (activity limitation, sleep problems, nasal symptoms, eye symptoms, non-nasal/eye symptoms, practical problems and emotional function). Subjects recalled how their rhinoconjunctivitis had been during the last week and responded to each question on a seven-point scale (0 = no impairment, 6 = maximum impairment). Questions were equally weighted, and the RQLQ score was the mean of the 28 questions and could range from zero to six. A higher score indicated greater impact on quality of life and thus a low score indicated a better outcome. | Weeks 50 to 52 after randomisation | 
| Participants Assessment of Change in Rhinoconjunctivitis Symptoms Measured by Rating Overall Symptoms at the End of the Study Relative to Baseline | A Global Impression of Change in Rhinoconjunctivitis Symptoms assessment was completed by subjects at the final follow-up visit. Subjects rated their overall allergy symptoms at the end of the study relative to baseline on a seven-point scale as follows:0. very much better; 1. moderately better; 2. a little better; 3. unchanged; 4. a little worse; 5. moderately worse; 6. very much worse. For reporting the individual categories were grouped as follows: moderately or very much better; any improvement; no change and any worsening. Subjects could therefore be reported in more than group and the total number reported does not match the overall number of participants analysed. | Weeks 50 to 52 after randomisation | 
| Mean TRSS in HDM-SPIRE Treatment Groups Compared With Placebo | Mean Total Rhinoconjunctivitis Symptom Score (TRSS) in HDM-SPIRE treatment groups compared with placebo. Eight symptoms are defined in the TRSS, 4 nasal symptoms: runny nose, sneezing; blocked nose, and itchy nose and 4 non-nasal symptoms: itchy eyes; watery eyes; red eyes, and sore eyes. Each symptom was rated in severity on a score of 0-3 (0. absent; 1. mild, barely noticeable; 2. moderate, annoying/troublesome; 3. severe, very annoying/very troublesome), therefore TRSS could range from 0 to 24. Higher TRSS reflected more severe symptom scores. Symptoms were scored daily for a period of approximately 3 weeks, 50-52 weeks after randomisation. | Weeks 50 to 52 after randomisation | 
| Mean Non-nasal Score in HDM-SPIRE Treatment Group Compared With Placebo | Mean daily Total Non-nasal Symptom Score (TNNSS) in HDM-SPIRE treatment groups compared to placebo. TNNSS was the sum of all the non-nasal symptom scores (itchy eyes; watery eyes; red eyes; sore eyes) and could range from 0 to 12. Higher TNNSS reflected more severe symptoms. Subjects rated the severity of each symptom over the last 24 hours as follows: 0. absent; 1. mild, barely noticeable; 2. moderate, annoying/troublesome; 3. severe, very annoying/very troublesome. Symptoms were scored daily for a period of approximately 3 weeks, 50-52 weeks after randomisation. | Weeks 50 to 52 after randomisation | 
| Mean Nasal Score in HDM-SPIRE Treatment Group Compared With Placebo | TNSS (Total nasal symptom score) was the sum of all the nasal symptom scores (runny nose; sneezing; blocked nose; itchy nose) and could range from 0 to 12. Higher TNSS reflected more severe symptoms. Subjects rated the severity of each symptom over the last 24 hours as follows: 0. absent; 1. mild, barely noticeable; 2. moderate, annoying/troublesome; 3. severe, very annoying/very troublesome. Symptoms were scored daily for a period of approximately 3 weeks, 50-52 weeks after randomisation. | Weeks 50 to 52 after randomisation | 
| Mean RMS in HDM-SPIRE Treatment Group Compared With Placebo | Mean RMS (Rescue medication score) in HDM-SPIRE treatment groups compared with placebo groups. The use of rhinoconjunctivitis rescue medications was recorded by the subject on a daily basis just before bedtime for approximately 21 days, 50-52 weeks after randomisation and was scored based on a previously published system as follows: 0 = no allergy rescue medication used per day; 0.5 = at least one dose of antihistamine eye drops used per day; 1 = at least one dose of oral antihistamine used per day; 2 = at least one dose of intranasal corticosteroid used per day; 3 = at least one dose of systemic corticosteroid used per day. The score was according to the highest level of rescue medication used and was not additive. | Weeks 50 to 52 after randomisation | 
| Number of Days With no Rescue Medication Use in HDM-SPIRE Treatment Group Compared With Placebo | The number of well days, i.e., days with no moderately or severely annoying symptoms and with no rescue medication used was calculated for all subjects over a period of approximately 21 days, 50-52 weeks after randomisation. | Weeks 50 to 52 after randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cat allergy, Rhinoconjunctivitis