Phase II HDM-SPIRE Safety and Efficacy Study

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02150343

Enrollment

715

Registered

2014-05-29

Start date

2014-09-30

Completion date

2017-04-13

Last updated

2018-06-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rhinoconjunctivitis

Keywords

Cat allergy, Rhinoconjunctivitis

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

Interventions

DRUGHDM-SPIRE

1 dose every 4 weeks

DRUGPlacebo

1 dose every 4 weeks

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.
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.
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.
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.

Countries

Canada, France, Germany, Italy, Netherlands, South Africa, Spain, United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
HDM-SPIRE 12 Nmol (4 Administrations) 12 nmol given at 4 weekly intervals (4 administrations)	180
HDM-SPIRE 20 Nmol 20 nmol given at 4 weekly intervals (4 administrations)	178
HDM-SPIRE 12 Nmol (8 Administrations) 20 nmol given at 4 weekly intervals (8 administrations)	178
HDM-SPIRE Placebo 8 administrations at 4 weekly intervals	178
Total	714

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	2	0	1	1
Overall Study	Lost to Follow-up	4	4	2	3
Overall Study	Other	2	6	0	2
Overall Study	Withdrawal by Subject	13	10	9	4

Baseline characteristics

Characteristic	HDM-SPIRE 12 Nmol (4 Administrations)	Total	HDM-SPIRE Placebo	HDM-SPIRE 12 Nmol (8 Administrations)	HDM-SPIRE 20 Nmol
Age, Continuous	36.7 years STANDARD_DEVIATION 11.53	36.8 years STANDARD_DEVIATION 12.12	36.8 years STANDARD_DEVIATION 12.84	35.5 years STANDARD_DEVIATION 11.61	38.3 years STANDARD_DEVIATION 12.4
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	7 Participants	32 Participants	10 Participants	3 Participants	12 Participants
Race (NIH/OMB) Black or African American	22 Participants	79 Participants	13 Participants	23 Participants	21 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants	46 Participants	19 Participants	7 Participants	12 Participants
Race (NIH/OMB) White	142 Participants	555 Participants	136 Participants	144 Participants	133 Participants
Sex: Female, Male Female	107 Participants	453 Participants	117 Participants	120 Participants	109 Participants
Sex: Female, Male Male	73 Participants	261 Participants	61 Participants	58 Participants	69 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 180	0 / 178	0 / 178	0 / 178
other Total, other adverse events	120 / 180	110 / 178	140 / 178	124 / 178
serious Total, serious adverse events	6 / 180	4 / 178	4 / 178	3 / 178

Outcome results

Primary

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.