Phase II HDM-SPIRE Safety and Efficacy Study

• Sponsor: Circassia Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02150343
• Collaborator: Quintiles, Inc. (Industry)
• Enrollment: 715
• Locations: 98
• Arms: 4
• Duration (Months): 31.4
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Rhinoconjunctivitis	Drug: HDM-SPIRE; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 715 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Apr 13, 2017
• Actual Study Completion Date: Apr 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HMD-SPIRE Treatment 1 4 x 12 nmol HDM-SPIRE followed by 4 x placebo 4 weeks apart	Drug: HDM-SPIRE; 1 dose every 4 weeks; Drug: Placebo; 1 dose every 4 weeks
Experimental: HDM-SPIRE Treatment 2 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; 1 dose every 4 weeks
Experimental: HDM-SPIRE Treatment 3 4 x 20 nmol HDM-SPIRE followed by 4 x placebo 4 weeks apart	Drug: HDM-SPIRE; 1 dose every 4 weeks; Drug: Placebo; 1 dose every 4 weeks
Placebo Comparator: Placebo 8 x placebo 4 weeks apart	Drug: Placebo; 1 dose every 4 weeks

Outcome Measures

Primary Outcome Measures

1. Combined Score of Symptoms and Allergy Medication [Weeks 50 to 52 after randomisation]

   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.

Secondary Outcome Measures

1. Mean RQLQ Score in HDM-SPIRE Treatment Groups Compared With Placebo [Weeks 50 to 52 after randomisation]

   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.

2. Participants Assessment of Change in Rhinoconjunctivitis Symptoms Measured by Rating Overall Symptoms at the End of the Study Relative to Baseline [Weeks 50 to 52 after randomisation]

   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.

3. Mean TRSS in HDM-SPIRE Treatment Groups Compared With Placebo [Weeks 50 to 52 after randomisation]

   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.

4. Mean Non-nasal Score in HDM-SPIRE Treatment Group Compared With Placebo [Weeks 50 to 52 after randomisation]

   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.

5. Mean Nasal Score in HDM-SPIRE Treatment Group Compared With Placebo [Weeks 50 to 52 after randomisation]

   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.

6. Mean RMS in HDM-SPIRE Treatment Group Compared With Placebo [Weeks 50 to 52 after randomisation]

   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.

7. Number of Days With no Rescue Medication Use in HDM-SPIRE Treatment Group Compared With Placebo [Weeks 50 to 52 after randomisation]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Huntington Beach	California	United States
3		Long Beach	California	United States
4		Mission Viejo	California	United States
5		Napa	California	United States
6		Orange	California	United States
7		Redwood City	California	United States
8		Rolling Hills Estates	California	United States
9		Roseville	California	United States
10		San Diego	California	United States
11		Walnut Creek	California	United States
12		Waterbury	Connecticut	United States
13		Tallahassee	Florida	United States
14		Tampa	Florida	United States
15		Stockbridge	Georgia	United States
16		Normal	Illinois	United States
17		Shiloh	Illinois	United States
18		Evansville	Indiana	United States
19		Iowa City	Iowa	United States
20		Owensboro	Kentucky	United States
21		Bangor	Maine	United States
22		Bethesda	Maryland	United States
23		Gaithersburg	Maryland	United States
24		Brockton	Massachusetts	United States
25		Minneapolis	Minnesota	United States
26		Plymouth	Minnesota	United States
27		Saint Louis	Missouri	United States
28		Bellevue	Nebraska	United States
29		Ocean City	New Jersey	United States
30		Teaneck	New Jersey	United States
31		Verona	New Jersey	United States
32		Rochester	New York	United States
33		Rockville Centre	New York	United States
34		Asheville	North Carolina	United States
35		High Point	North Carolina	United States
36		Canton	Ohio	United States
37		Cincinnati	Ohio	United States
38		Tulsa	Oklahoma	United States
39		Medford	Oregon	United States
40		Portland	Oregon	United States
41		Bethlehem	Pennsylvania	United States
42		Blue Bell	Pennsylvania	United States
43		Pittsburgh	Pennsylvania	United States
44		Providence	Rhode Island	United States
45		Dallas	Texas	United States
46		Kerrville	Texas	United States
47		Plano	Texas	United States
48		San Antonio	Texas	United States
49		South Burlington	Vermont	United States
50		Henrico	Virginia	United States
51		Bellingham	Washington	United States
52		Seattle	Washington	United States
53		Vancouver	Washington	United States
54		Greenfield	Wisconsin	United States
55		Madison	Wisconsin	United States
56		Milwaukee	Wisconsin	United States
57		Hamilton	Ontario	Canada
58		London	Ontario	Canada
59		Niagara	Ontario	Canada
60		Ottawa	Ontario	Canada
61		Toronto	Ontario	Canada
62		Windsor	Ontario	Canada
63		Montreal	Quebec	Canada
64		Quebec City	Quebec	Canada
65		St Romuald	Quebec	Canada
66		Trois Rivieres	Quebec	Canada
67		Reims	Marne	France
68		Gironde	Pessac	France
69		Bas Rhin	Strasbourg	France
70		Meurthe-et-Moselle	Vandoeuvre Les Nancy	France
71		Heidelberg	Baden Wuerttemberg	Germany
72		Essen	Nordrhein Westfalen	Germany
73		Goch	Nordrhein Westfalen	Germany
74		Dresden	Saxony	Germany
75		Berlin		Germany
76		Hamburg		Germany
77		Ancona	Torrette Di Ancona	Italy
78		Genova		Italy
79		Milano		Italy
80		Parma		Italy
81		Pavia		Italy
82		Roma		Italy
83		Siena		Italy
84		Almere		Netherlands
85		Amsterdam		Netherlands
86		Beek		Netherlands
87		Durban	KwaZulu-Natal	South Africa
88		Ottawa	KwaZulu-Natal	South Africa
89		Umkomaas	KwaZulu-Natal	South Africa
90		Cape Town	Western Cape	South Africa
91		Sabadell	Barcelona	Spain
92		Santander	Cantabria	Spain
93		Girona	Catalonia	Spain
94		San Sebastian	Guipuzcoa	Spain
95		Pamplona	Navarre	Spain
96		Bilbao	Vizcaya	Spain
97		Barcelona		Spain
98		Sevilla		Spain

Sponsors and Collaborators

• Circassia Limited
• Quintiles, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 1, 2015
• Statistical Analysis Plan - Mar 24, 2017

More Information

Publications

None provided.

• Responsible Party: Circassia Limited
• ClinicalTrials.gov Identifier: NCT02150343
• Other Study ID Numbers: TH005
• First Posted: May 29, 2014
• Last Update Posted: Jun 15, 2018
• Last Verified: May 1, 2018

• Keywords provided by Circassia Limited: Cat allergy; Rhinoconjunctivitis
• Additional relevant MeSH terms: Conjunctivitis

Study Results

Participant Flow

Pre-assignment Detail	715 participants were randomised on to the study through the IRT. However, one participant was inadvertently randomised before eligibility had been confirmed by the PI, and was withdrawn due to a finding of inspiration/expiration wheeze before receiving any study medication. Therefore results refer to 714 participants throughout.

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Period Title: Overall Study
STARTED	180	178	178	178
COMPLETED	159	158	166	168
NOT COMPLETED	21	20	12	10

Baseline Characteristics

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo	Total
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals	Total of all reporting groups
Overall Participants	180	178	178	178	714
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.7 (11.53)	38.3 (12.40)	35.5 (11.61)	36.8 (12.84)	36.8 (12.12)
Sex: Female, Male (Count of Participants)
Female	107 59.4%	109 61.2%	120 67.4%	117 65.7%	453 63.4%
Male	73 40.6%	69 38.8%	58 32.6%	61 34.3%	261 36.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.6%	0 0%	1 0.6%	0 0%	2 0.3%
Asian	7 3.9%	12 6.7%	3 1.7%	10 5.6%	32 4.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	22 12.2%	21 11.8%	23 12.9%	13 7.3%	79 11.1%
White	142 78.9%	133 74.7%	144 80.9%	136 76.4%	555 77.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	8 4.4%	12 6.7%	7 3.9%	19 10.7%	46 6.4%

Outcome Measures

1. Primary Outcome

Title	Combined Score of Symptoms and Allergy Medication
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	159	165	168
Least Squares Mean (Standard Error) [units on a scale]	1.69 (0.089)	1.51 (0.089)	1.40 (0.086)	1.56 (0.087)

2. Secondary Outcome

Title	Mean RQLQ Score in HDM-SPIRE Treatment Groups Compared With Placebo
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	158	166	167
Least Squares Mean (Standard Error) [units on a scale]	2.02 (0.098)	1.76 (0.098)	1.72 (0.095)	1.89 (0.095)

3. Secondary Outcome

Title	Participants Assessment of Change in Rhinoconjunctivitis Symptoms Measured by Rating Overall Symptoms at the End of the Study Relative to Baseline
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

The overall number of participants analysed represents the number of subjects that completed the assessment, not all subjects that completed the study (651) completed the Clinical Global Impression of Change (633).

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	159	156	158	160
Moderately or very much better	55 30.6%	70 39.3%	61 34.3%	64 36%
Any improvement	101 56.1%	109 61.2%	103 57.9%	109 61.2%
No Change	45 25%	41 23%	48 27%	43 24.2%
Any worsening	13 7.2%	6 3.4%	7 3.9%	8 4.5%

4. Secondary Outcome

Title	Mean TRSS in HDM-SPIRE Treatment Groups Compared With Placebo
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	159	165	168
Least Squares Mean (Standard Error) [units on a scale]	8.96 (0.468)	8.03 (0.467)	7.97 (0.451)	8.16 (0.455)

5. Secondary Outcome

Title	Mean Non-nasal Score in HDM-SPIRE Treatment Group Compared With Placebo
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	159	165	168
Least Squares Mean (Standard Error) [units on a scale]	3.99 (0.242)	3.64 (0.242)	3.53 (0.233)	3.73 (0.235)

6. Secondary Outcome

Title	Mean Nasal Score in HDM-SPIRE Treatment Group Compared With Placebo
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	159	165	168
Least Squares Mean (Standard Error) [units on a scale]	4.99 (0.244)	4.40 (0.243)	4.45 (0.235)	4.44 (0.237)

7. Secondary Outcome

Title	Mean RMS in HDM-SPIRE Treatment Group Compared With Placebo
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	159	165	168
Least Squares Mean (Standard Error) [units on a scale]	0.57 (0.048)	0.51 (0.048)	0.41 (0.047)	0.55 (0.047)

8. Secondary Outcome

Title	Number of Days With no Rescue Medication Use in HDM-SPIRE Treatment Group Compared With Placebo
Description	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.
Time Frame	Weeks 50 to 52 after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)	HDM-SPIRE 20 Nmol	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (4 administrations)	20 nmol given at 4 weekly intervals (8 administrations)	8 administrations at 4 weekly intervals
Measure Participants	160	159	165	168
Least Squares Mean (Standard Error) [Days]	25.9 (2.90)	33.5 (2.89)	33.9 (2.80)	31.1 (2.812)

Adverse Events

Time Frame	Upto 52 weeks after randomisation
Arm/Group Title	HDM-SPIRE 12 Nmol (4 Administrations)		HDM-SPIRE 20 Nmol		HDM-SPIRE 12 Nmol (8 Administrations)		HDM-SPIRE Placebo
Arm/Group Description	12 nmol given at 4 weekly intervals (4 administrations)		20 nmol given at 4 weekly intervals (4 administrations)		20 nmol given at 4 weekly intervals (8 administrations)		8 administrations at 4 weekly intervals
All Cause Mortality
	HDM-SPIRE 12 Nmol (4 Administrations)		HDM-SPIRE 20 Nmol		HDM-SPIRE 12 Nmol (8 Administrations)		HDM-SPIRE Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/180 (0%)		0/178 (0%)		0/178 (0%)		0/178 (0%)
Serious Adverse Events
	HDM-SPIRE 12 Nmol (4 Administrations)		HDM-SPIRE 20 Nmol		HDM-SPIRE 12 Nmol (8 Administrations)		HDM-SPIRE Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/180 (3.3%)		4/178 (2.2%)		4/178 (2.2%)		3/178 (1.7%)
Blood and lymphatic system disorders
Leukocytosis	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0
Cardiac disorders
Angina pectoris	1/180 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0	0/178 (0%)	0
Gastrointestinal disorders
Colitis	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0
Large intestine perforation	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0
General disorders
Non-cardiac chest pain	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	1/178 (0.6%)	1
Hepatobiliary disorders
Cholecystitis	1/180 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0	0/178 (0%)	0
Infections and infestations
Campylobacter gastroenteritis	0/180 (0%)	0	0/178 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1
Diverticulitis	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	1/178 (0.6%)	1
Sinusitis	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0
Cellulitis	0/180 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0
Wound infection	0/180 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0
Injury, poisoning and procedural complications
Urinary retention postoperative	0/180 (0%)	0	0/178 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1
Postoperative wound complication	1/180 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0	0/178 (0%)	0
Jaw fracture	1/180 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0	0/178 (0%)	0
Lower limb fracture	0/180 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0
Post procedual haemorrhage	0/180 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0
Psychiatric disorders
Psychotic disorder	1/180 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0	0/178 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/180 (0.6%)	1	0/178 (0%)	0	0/178 (0%)	0	0/178 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/180 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0
Skin reaction	0/180 (0%)	0	0/178 (0%)	0	1/178 (0.6%)	1	0/178 (0%)	0
Other (Not Including Serious) Adverse Events
	HDM-SPIRE 12 Nmol (4 Administrations)		HDM-SPIRE 20 Nmol		HDM-SPIRE 12 Nmol (8 Administrations)		HDM-SPIRE Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	120/180 (66.7%)		110/178 (61.8%)		140/178 (78.7%)		124/178 (69.7%)
Infections and infestations
Nasopharyngitis	37/180 (20.6%)	59	32/178 (18%)	54	38/178 (21.3%)	54	41/178 (23%)	58
Upper respiratory tract infection	22/180 (12.2%)	27	24/178 (13.5%)	32	21/178 (11.8%)	32	20/178 (11.2%)	26
Sinusitis	13/180 (7.2%)	16	14/178 (7.9%)	15	15/178 (8.4%)	15	12/178 (6.7%)	16
Influenza	7/180 (3.9%)	7	12/178 (6.7%)	15	15/178 (8.4%)	15	11/178 (6.2%)	12
Urinary tract infection	5/180 (2.8%)	6	7/178 (3.9%)	7	10/178 (5.6%)	14	6/178 (3.4%)	9
Bronchitis	9/180 (5%)	9	4/178 (2.2%)	4	6/178 (3.4%)	8	7/178 (3.9%)	7
Nervous system disorders
Headache	10/180 (5.6%)	26	11/178 (6.2%)	30	13/178 (7.3%)	28	12/178 (6.7%)	16
Respiratory, thoracic and mediastinal disorders
Cough	11/180 (6.1%)	11	4/178 (2.2%)	4	8/178 (4.5%)	9	9/178 (5.1%)	11
Oropharyngeal pain	6/180 (3.3%)	7	2/178 (1.1%)	2	14/178 (7.9%)	14	6/178 (3.4%)	9

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Wording included in the clinical protocol - The Investigator and Circassia will normally prepare a manuscript together. To avoid disclosures that may affect the proprietary rights of the Sponsor, the Investigator agrees to allow Circassia the opportunity to review all manuscripts and abstracts 60 days prior to submission for publication. Circassia reserves the right to include the report of this study in any regulatory documentation or submission or in any informational materials.