Efficacy and Safety Trial of Pangramin SLIT HDM-mix in Subjects With House Dust Mite Induced Rhinitis

Phase 3

Completed

Conditions: Allergic Rhinitis

Interventions: Biological: Placebo
Biological: Pangramin SLIT HDM mix.

Registration Number: NCT01603056

Lead Sponsor: ALK-Abelló A/S

Brief Summary: Primary aim is to evaluate the efficacy of specific immunotherapy with Pangramin SLIT HDM-mix compared to placebo in the treatment of House Dust Mite (HDM) induced rhinitis with or without asthma.

Sublingual immunotherapy has been used during several years and has been shown to provide benefits compare to traditional subcutaneous treatment. This study will investigate if improvements in rhinitis symptoms and less use of symptomatic medication can be obtained as a consequence of being treated under specific immunotherapy.

This study aim also to contribute to the documentation of tolerability and safety profile of Pangramin HDM Mix.

Detailed Description: Extensive clinical experience has been gained due to the widespread use of Pangramin® SLIT and other SLIT products as named patient products, both with respect to the types and the frequencies of the adverse events(AEs) observed. No safety concerns have been found.

The optimal therapeutic dose range regarding SLIT is not fully elucidated. The fate of the allergen after sublingual administration is not known in detail, i.e. to what extent is the allergen absorbed over the mucosa or swallowed and how this is related to volume, excipients etc. The relationship between dose and effect is thus not fully elucidated. The general recommendation is to use a dose inducing a clinical relevant effect in most patients without causing unacceptable adverse events. As Pangramin SLIT HDM-mix has a safety profile that allows a single daily intake by the patient at home, the dosage at this trial will be the same as marketed product.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 617

Inclusion Criteria

Male or female ≥ 5 to ≤ 55 years of age.
A history HDM induced allergic rhinitis.
Use of medication for the control of rhinoconjunctivitis symptoms.
Positive Skin Prick Test (SPT).
Positive specific IgE.

Exclusion Criteria

PEF ≤ 70% of predicted value.
History of significant symptomatic seasonal or perennial allergic rhinitis and/or asthma caused by an allergen to which the patient is regularly exposed, and sensitized (e.g. pollens, cat, dog, cockroach...except house dust mites).
Severe asthma.
Current symptoms of upper respiratory tract infection or other relevant infectious process.
Current food allergies with oral allergy syndrome.
A clinical history of chronic sinusitis.
Current severe atopic dermatitis.
Concomitant or previous treatment by immunotherapy.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo Up-dosing phase (vial 0 to vial 4) + maintenance phase (3 times per week), for 12 months.
PANGRAMIN SLIT HDM MIX	Pangramin SLIT HDM mix.	PANGRAMIN SLIT HDM MIX Up-dosing phase (vial 0 to vial 4) + maintenance phase (3 times per week), for 12 months.

Primary Outcome Measures

Name	Time	Method
The Change From Baseline in Rhinoconjunctivitis Medication Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects were provided with open-labelled rescue medication to be used as needed for treatment of their rhinoconjunctivitis symptoms. Subjects reported their use of specific rescue medication via the patient diary cards. Scoring principles were applied to transform the number of rescue medication doses used into medication scores.The scores of all the medication used were summed to produce the daily rhinoconjunctivitis medication score range from 0 to 32. A lower medication score means the patient use less medication, and represent a better outcome; on the contrary, a higher medication score means the patient use more medication, and represent a worse outcome. Baseline was from V1 (Week -8) to V2 (Week 0). The end evaluation period was set from V8(Week 44) to V9(Week 52). These two average scores (Baseline and End) were calculated for each patient as the sum of the daily score throughout the 2 months(8 weeks in count) in evaluation period and divided with the days in diary.
The Change From Baseline in Rhinoconjunctivitis Symptoms Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects completed symptom assessments and recorded the results in the patient diary cards on a daily basis. A total of six rhinoconjunctivitis symptoms were measured on a scale from 0-3 as follows: 0 = No symptoms. 1. = Mild symptoms. 2. = Moderate symptoms. 3= Severe symptoms. The six symptoms are classified in 2 groups as follows: Nose symptoms: Runny nose, Blocked nose, Sneezing, Itchy nose; Eye symptoms: Gritty feeling/red/itchy eyes, Watery eyes. The six symptom scores were summed to obtain the rhinoconjunctivitis symptoms score with range 0(best) to 18(worst). Baseline was set as 8 weeks before randomization as from V1 (Week -8) to V2 (Week 0). 11-12months' end evaluation period was set from V8(Week 44) to V9(Week 52). These two average rhinoconjunctivitis symptoms scores (Baseline and 11-12months) were calculated for each patient as the sum of the daily score throughout the 2 months(8 weeks in count) in evaluation period and divided with the days with diary.

Secondary Outcome Measures

Name	Time	Method
The Change From Baseline in Rhinitis Symptom Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects were instructed by the investigator on how to complete symptom assessments and recorded the results in the patient diary cards on a daily basis. A total of 4 rhinitis symptoms were measured on a scale from 0-3 as follows: 0 = No symptoms. 1. = Mild symptoms. 2. = Moderate symptoms. 3= Severe symptoms. The 4 symptoms are as follows: Runny nose, Blocked nose, Sneezing, Itchy nose. The 4 symptom scores were summed to obtain the rhinitis symptoms score with range 0(best) to 12(worst). Baseline was set as 8 weeks before randomization as from V1 (Week -8) to V2 (Week 0). 11-12months' end evaluation period was set from V8(Week 44) to V9(Week 52). These two average scores (Baseline and 11-12months) were calculated for each patient as the sum of the daily score throughout the 2 months(8 weeks in count) in evaluation period and divided with the days with diary.
The Change From Baseline in Conjunctivitis Symptom Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects were instructed by the investigator on how to complete symptom assessments and recorded the results in the patient diary cards on a daily basis. A total of 2 conjunctivitis symptoms were measured on a scale from 0-3 as follows: 0 = No symptoms. 1. = Mild symptoms. 2. = Moderate symptoms. 3= Severe symptoms. The 2 symptoms as follows: Gritty feeling/red/itchy eyes, Watery eyes. The 2 symptom scores were summed to obtain the conjunctivitis symptoms score with range 0(best) to 6(worst). Baseline was set as 8 weeks before randomization as from V1 (Week -8) to V2 (Week 0). 11-12months' end evaluation period was set from V8(Week 44) to V9(Week 52). These two average scores (Baseline and 11-12months) were calculated for each patient as the sum of the daily score throughout the 2 months(8 weeks in count) in evaluation period and divided with the days with diary.
The Change From Baseline in Asthma Symptom Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects were instructed by the investigator on how to complete symptom assessments and recorded the results in the patient diary cards on a daily basis. A total of 4 Asthma symptoms were measured on a scale from 0-3 as follows: 0 = No symptoms. 1. = Mild symptoms. 2. = Moderate symptoms. 3= Severe symptoms. The 4 symptoms as follows: Cough, Wheeze, Chest tightness/shortness of breath (dyspnoea), Exercise induced symptoms. The 4 symptom scores were summed to obtain the asthma symptoms score with range 0(best) to 12(worst). Baseline was set as 8 weeks before randomization as from V1 (Week -8) to V2 (Week 0). 11-12months' end evaluation period was set from V8(Week 44) to V9(Week 52). These two average scores (Baseline and 11-12months) were calculated for each patient as the sum of the daily score throughout the 2 months(8 weeks in count) in evaluation period and divided with the days with diary.
Percentage of Healthy Days in This Study Between the Actively Treated Patients and the Placebo Treated.	Total study year	A healthy day is a day without rhinoconjunctivitis symptoms and without any intake of rescue medication. Percentage of healthy days is the healthy days of subject in this study divided by the total study days.
The Change From Baseline in Nasal Complain Scores on Visual Analog Scale at 11-12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	The average rhinoconjunctivitis VAS score (baseline to first year). The scale answers the question 'How have your nasal complaints been today?' from 0 = no symptoms to 10 = severe symptoms. The baseline VAS rhinoconjunctivitis score is the average value of VAS scores in V1 (Screen Visit, Week -8) and V2 (Randomization visit, Week 0), and Evaluation period (Months 11-12) VAS rhinoconjunctivitis score is the average value of VAS scores in V8 (Week 44) and V9 (Week 52).
The Change From Baseline in Rhinitis Quality of Life Questionnaire at 12 Months Between the Actively Treated Patients and the Placebo Treated.	Visit 1 date(Week -8), Visit 9 date(Week 52).	The baseline RQLQ value was collected in Visit 1 (Week -8) and the 12 months' RQLQ value was collected in Visit 9 (Week 52). The maximum value of RQLQ score is 168 and the minimum one is 0. The score is decreased as the life quality is better.
Global Assessment of Rhinoconjunctivitis Symptom After Treatment Between the Actively Treated Patients and the Placebo Treated.	Visit 9 date, Week 52	Comparing overall rhinoconjunctivitis symptoms at the end of study year Between the Actively Treated Patients and the Placebo Treated.
The Change From Baseline in Rhinitis Medication Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated.	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects were provided with open-labelled rescue medication to be used as needed for treatment of their Rhinitis symptoms. Subjects reported their use of specific rescue medication via the patient diary cards. Scoring principles were applied to transform the number of rescue medication doses used into medication scores. The scores of all the medication used were summed to produce the daily Rhinitis medication score range from 0 to 30. A lower medication score means the patient use less medication, and represent a better outcome; on the contrary, a higher medication score means the patient use more medication, and represent a worse outcome. Baseline was set as from V1 (Week -8) to V2 (Week 0). 11-12months' end evaluation period was set from V8(Week 44) to V9(Week 52). These two average scores (Baseline and 11-12months) were calculated for each patient as the sum of the daily score throughout the 2 months(8 weeks in count) in evaluation period and divided with the days with diary.
The Change From Baseline in Asthma Quality of Life Questionnaire at 12 Months Between the Actively Treated Patients and the Placebo Treated.	Visit 1 date(Week -8), Visit 9 date(Week 52).	The baseline AQLQ value was collected in Visit 1 (Week -8) and the 12 months' RQLQ value was collected in Visit 9 (Week 52). The maximum value of RQLQ score is 217 and the minimum one is 0. The score is elevated as the life quality is better.
The Change From Baseline in Asthma Medication Score at 11 - 12 Months Between the Actively Treated Patients and the Placebo Treated	Baseline: From V1 date(Week -8) to V2 date(Week 0); 11-12months: From V8 date(Week 44) to V9 date(Week 52).	Subjects were provided with open-labelled rescue medication to be used as needed for treatment of their Asthma symptoms. Subjects reported their use of specific rescue medication via the patient diary cards. Scoring principles were applied to transform the number of rescue medication doses used into medication scores. The scores of all the medication used were summed to produce the daily asthma medication score range from 0 to 32. A lower medication score means the patient use less medication, and represent a better outcome; on the contrary, a higher medication score means the patient use more medication, and represent a worse outcome. Baseline was set as from V1 (Week -8) to V2 (Week 0). 11-12months' end evaluation period was set from V8(Week 44) to V9(Week 52). These two average scores (Baseline and 11-12months) were calculated for each patient as the sum of the daily score throughout the 2 months in evaluation period and divided with the days with diary.