Allergic rhinitis/rhinoconjunctivitis (ARC) caused by house dust mite (HDM) allergy. MedDRA version: 20.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853 MedDRA version: 20.0 Level: LLT Classification code 10001724 Term: Allergic rhinitis (excl hay fever) System Organ Class: 100000004855
Conditions
Interventions
Product Name: PURETHAL® Mites
Pharmaceutical Form: Suspension for injection
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use
Sponsors
HAL Allergy B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients who signed their informed consent form. 2. Patients aged =18 and =65 years at signing of informed consent form. 3. Patients with moderate to severe HDM-induced allergic rhinitis or rhinoconjunctivitis (based on ARIA classification) for at least one year prior to screening; with or without concomitant asthma (asthma must be controlled (GINA 2010)). 4. Patients with a history of concomitant asthma must have an FEV1 >70% of predicted value, at screening. Patients without a history of asthma must have an FEV1 >70% or a PEF >80% of predicted value at screening. 5. Patient that reported a mean CSMS(n) =1.5 during the baseline period. 6. Patients that are willing and capable to complete an e-diary daily during 12 weeks of the study (=60% compliance in e-diary completion during the 14 days baseline period). 7. Patients with a positive SPT for HDM D. pter or D. far (mean wheal diameter =3 mm compared to negative control; for negative control a reaction up to 2 mm is allowed; histamine control should be positive (mean wheal diameter =3 mm) assessed during screening or a documented positive response obtained within one year before screening. 8. Patients with an allergen specific serum IgE (ssIgE) level for HDM D. pter or D. far of =0.7 U/mL assessed during screening. 9. Patients with a positive NPT for HDM D. pter extract during screening (Lebel score =6 at 10,000 AU/mL), test should be postponed if baseline score is = 3 or if negative control is >3. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 730 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with concomitant sensitization i.e. positive SPT (mean wheal diameter =3 mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter =3 mm)) to other allergens than HDM, if they have expected clinically relevant symptoms related to the other allergen, overlapping with either the 8-week efficacy assessment period and/or the screening/baseline period, based on the judgement of the investigator. 2. Patients sensitized and symptomatic to pets, that will be regularly exposed to pets during the study period. 3. Patients with a history of anaphylaxis with cardio-respiratory symptoms (food allergy, drugs or an idiopathic reaction). 4. Patients who received immunotherapy (SCIT or SLIT) with HDM allergens within the past 5 years. 5. Patients with unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the past 5 years (e.g., but not limited to, prematurely stopped immunotherapy due to non-compliance, AEs, or lack of therapeutic effect). 6. Patients who undergo allergen-specific immunotherapy (SCIT or SLIT) with other allergens than HDM during the study period (screening up to EoS). 7. Patients who participated in a clinical interventional study within the last 3 months (e.g. new investigational drug or biological) or in an observational study within the last 30 days (e.g. post marketing study), or plans on participating in another clinical trial during the duration of this study, at the discretion of the investigator. 8. Patients that (will) receive any vaccination (including influenza vaccine) one week before start of treatment and/or during the up-dosing phase. 9. Patients undergoing any immunosuppressive treatment (e.g. anti-IgE therapy) within the last 6 months prior to inclusion and up to EoS. 10. Patients suffering from severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs. 11. Patients suffering from active malignancies or any malignant disease during 5 years prior to screening. 12. Patients suffering from any chronic or acute disease that in the opinion of the investigator might place the patient at an additional risk, including but not limited to the following: clinically significant abnormal ECG at screening or cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, haematological disorders, severe atopic dermatitis, active tuberculosis. 13. Patients suffering from any disease with a contra-indication for the use of epinephrine/adrenaline (e.g. hyperthyroidism, glaucoma). 14. Patients receiving treatment with systemic corticosteroids, nasal corticosteroids, antihistamines or aluminium containing medication during the indicated timeframe as listed in Table 4 of the protocol. 15. Patients receiving treatment with systemic or local beta-blockers (including beta-blocker containing eye drops) any time during the study. 16. Patients suffering from moderate to severe nasal obstructive disease such as polyps, septum deviations, etc. 17. Patients suffering from clinically significant chronic sinusitis or ocular infection. 18. Female patients of child-bearing potential who are pregnant, lactating or using inadequate contraceptive measures. Contraceptive measures considered adequate are: 1) hormonal contraceptives such as contraceptive pills, transdermal patches, intrauterine device (IUD
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess clinical efficacy of 50,000 AUeq/mL (0.5 mL) PM SCIT, compared to placebo, in patients suffering from HDM-induced ARC, measured by the combined symptom and medication score (CSMS(n)) during the last 8 weeks of approximately 1 year treatment. For this primary CSMS(n) evaluation, the symptom score of the CSMS(n) will be based on nasal symptoms only. ;Secondary Objective: • To assess clinical efficacy of PM, compared to placebo, measured by the: o dSS(n) (mean individual daily symptom scores, nasal symptoms only) assessed during the last 8 weeks of the approximately 1 year treatment period; o dMS (mean daily medication score) assessed during the last 8 weeks of the approximately 1 year treatment period; o Difference in NPT (nasal provocation test) at the end of study compared to baseline. • To determine the onset of efficacy based on CSMS(n) for PM vs placebo. • To compare the proportion of ‘symptom-free days’ (i.e. days without nasal symptoms) and ‘troubled days’ (i.e. days with CSMS(n) = 1.5), assessed during the last 8 weeks of the approximately 1 year treatment period. • To assess the effect of PM, compared to placebo, on Quality of Life (QoL) after approximately 1 year of treatment. • To assess the effect of PM, compared to placebo, on serum specific immunoglobulin levels. ;Primary end point(s): The primary endpoint is the Combined Symptom (nasal symptoms only) and Medication Score CSMS(n). The primary evaluation of the CSMS(n) includes only nasal symptoms; itchy nose, sneezing, runny nose, and blocked nose (all rated from 0-3), and the medication score; 1 for oral and/or topical antihistamines, 2 for intranasal corticosteroids, and 3 for oral corticosteroids. The eye symptoms will not be taken into account in the primary evaluation, because these are less relevant for HDM induced allergies (23). The scores from the four nasal symptoms are added and divided by 4 to a total daily symptom score (dSS(n)) from 0-3 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • dSS(n) (nasal symptoms only), measured during the last 8 weeks of the approximately 1 year treatment period. • dMS measured during the last 8 weeks of the approximately 1 year treatment period. • Difference in change from baseline in NPT outcome (Lebel score). • Onset of efficacy based on CSMS(n), measured during the two one-week periods during treatment and during the last 8 weeks of the approximately 1 year treatment period. • Proportion of ‘symptom-free days’ (i.e. days without nasal symptoms) and ‘troubled days’ (i.e. days with CSMS(n) = 1.5), assessed during the last 8 weeks of the approximately 1 year treatment period. • QoL measured with the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ-S) and EQ-5D-5L questionnaire, for all patients; and an additional asthma control questionnaire (ACQ, for patients with concomitant asthma only) as measured at the end of treatment. • Difference from baseline in serum specific immunoglobulin levels (IgE, IgG, IgG4) between PM and placebo, during and after treatment. Safety • Safety and tolerability assessed by: o local and systemic reactions o (serious) adverse events o blood safety biochemistry/haematology parameters (including aluminium content) o urinalysis (including aluminium content) o vital signs o ECG in PM compared to placebo, as measured before, during and after treatment. Exploratory • Difference in CSMS (nasal and conjunctival symptoms) between PM and placebo, measured during the last 8 weeks of the approximately 1 year treatment period. • dSS (nasal and conjunctival symptoms), measured during the last 8 weeks of the approximately 1 year treatment period. • Difference in QoL measured with the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ-S) and EQ-5D-5L questionnaire, for all patients; and an additional asthma control questionnaire (ACQ, for patients wit | — |
Countries
Belgium, Germany, Hungary, Portugal, Slovakia, Spain
Contacts
Public ContactClinical Trial Manager
HAL Allergy B.V.
Outcome results
None listed