Phase III trial of specific immunotherapy with allergoid preparation of house dust mite in patients with allergic bronchial asthma and with allergic rhinitis or rhinoconjunctivitis

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2015-000188-15-ES
• Date of registration: 09/12/2016
• Prospective Registration: Yes
• Primary sponsor: Allergopharma GmbH & Co. KG
• Public title: Phase III trial of specific immunotherapy with allergoid preparation of house dust mite in patients with allergic bronchial asthma and with allergic rhinitis or rhinoconjunctivitis
• Scientific title: A multicenter randomized double-blind adaptive placebo-controlled clinical trial for evaluation of efficacy and safety of specific immunotherapy with an aluminium hydroxide-adsorbed allergoid preparation of house dust mite (Dermatophagoides pteronyssinus) in patients with allergic bronchial asthma and with allergic rhinitis or rhinoconjunctivitis
• Date of first enrolment: 23/12/2016
• Target sample size: 444
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000188-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, Croatia, Germany, Latvia, Lithuania, Poland, Russian Federation, Serbia, Spain, Ukraine

Contacts

• Name: Clinical Project Manager
• Affiliation: Allergopharma GmbH & Co. KG

• Name: Clinical Project Manager
• Affiliation: Allergopharma GmbH & Co. KG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent and assent according to local requirements before any trial-related activities started (a trial-related activity is any procedure that would not have been performed during the routine management of the patient.)
2. Male or female outpatient between 12 and 65 years (both inclusive)
3. IgE-mediated allergic bronchial asthma treated according GINA step 2-4 with rhinitis or rhinoconjunctivitis induced by house dust mite documented by
• SPT wheal for D p = 3 mm in diameter
• histamine (0.1% histamine) wheal = 3 mm
• a negative control reaction (NaCl) wheal < 2 mm
• Immunoassay result specific IgE > 1.5 kU/L to D p
• symptoms of asthma and rhinitis or rhinoconjunctivitis e.g. during the months September to February or over the entire year
4. confirmed diagnosis of asthma
• treatment according to GINA 2015 during the last year as documented by requirement of ICS and requirement of a bronchodilator
• FEV1 increase of = 12% and 200 mL of the baseline FEV1 after inhalation of 400µg of Salbutamol or other short acting bronchodilator equivalent (historical data not older than 2 years are acceptable)
• Achievement of asthma control criteria (ACQ6 = 1.0 scores in 2 consecutive weeks at the end of the assessment period) during the baseline diary phase within a required ICS dose between 400 to 1200 µg Budesonide per day
Are the trial subjects under 18? yes
Number of subjects for this age range: 133
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 311
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
General criteria:
1. Unable to understand and comply with the requirements of the trial, as judged by the investigator
2. Currently participating in any other trial or in participating in any other trial within 30 days before inclusion in this trial
3. Low compliance, persistent incorrect inhaler technique as assessed by the investigator or inability to understand instructions or trial documents
4. Involved in the planning and conduct of the trial
5. Employee of Allergopharma GmbH & Co. KG or of one of the trial sites
6. Any relationship of dependence with the sponsor or with the investigator
7. Previously enrolled or randomized to treatment in the present trial
8. Mentally disabled
9. Institutionalized due to an official or judicial order
For females with childbearing potential (i.e. females who are not chemically or surgically sterilized or females who are not post-menopausal):
10. Positive pregnancy test
11. Use of an unacceptable or unreliable contraceptive method during the trial, as judged by the investigator (reliable and highly effective methods of birth control defined as failure rate less than 1% per year)
12. Pregnant, breast feeding or wishes to breast feed
13. Seeking to become pregnant during the course of the trial
Immunotherapy criteria:
14. Any AIT with house dust mites
15. Current treatment with any kind of immunotherapy
16. Any AIT with unknown allergen
17. Clinically relevant symptoms to other regional specific allergens which interfere with the assessment period of October to January. Exceptions are symptoms to allergens of cat and dog, if the patient has no direct contact to these animals.
18. Sensitization in the immunoassay = 0.7 kU/L against region specific allergens which interfere with the assessment period of October to January. Exceptions are sensitizations to storage mites if the sensitization assessed by immunoassay is lower than the sensitization to at least one of the house dust mites (D p or D f). Exceptions are sensitizations assessed by immunoassay to cat and dog, if the patient has no direct contact to these animals.
Diseases and health status:
19. Clinically relevant rhinitis or respiratory symptoms related to other reasons (e.g. chronic sinusitis, COPD)
20. FEV1 < 70% of predicted normal (ECSC)[17]
21. Asthma or rhinitis symptoms for 20 years or longer
And the usual exclusion criteria for immunotherapy regarding health status and medical requirement.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

allergic bronchial asthma and allergic rhinitis or rhinoconjunctivitis
MedDRA version: 19.0 Level: LLT Classification code 10039097 Term: Rhinoconjunctivitis System Organ Class: 100000004862
MedDRA version: 19.0 Level: LLT Classification code 10001705 Term: Allergic asthma System Organ Class: 100000004855
MedDRA version: 19.0 Level: LLT Classification code 10001723 Term: Allergic rhinitis System Organ Class: 100000004855

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: House dust mite allergoid (Dermatophagoides pteronyssinus)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: House dust mite allergoid (Dermatophagoides pteronyssinus)
Other descriptive name: DERMATOPHAGOIDES PTERONYSSINUS
Concentration unit: PNU/ml protein nitrogen units/millilitre
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use

Product Name: House dust mite allergoid (Dermatophagoides pteronyssinus)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: House dust mite allergoid (Dermatophagoides pteronyssinus)
Other descriptive name: DERMATOPHAGOIDES PTERONYSSINUS
Concentration unit: PNU/ml protein nitrogen units/millilitre
Concentration type: equal
Concentration number: 900-
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use

Product Name: House dust mite allergoid (Dermatophagoides pteronyssinus)
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: House dust mite allergoid (Dermatophagoides pteronyssinus)
Other descriptive name: DERMATOPHAGOIDES PTERONYSSINUS
Concentration unit: PNU/ml protein nitrogen units/millilitre
Concentration type: equal
Concentration number: 5000-
Pharmaceutical for

Primary Outcome(s)

Main Objective: The aim of this clinical trial is to demonstrate efficacy and to evaluate safety of AIT with an aluminium hydroxide adsorbed allergoid preparation of major allergens of D p in patients with allergic bronchial asthma (acc. to GINA 2015) and allergic rhinitis or rhinoconjunctivitis caused by house dust mites.

Secondary Objective: None

Primary end point(s): This is a confirmatory phase III pivotal study. The primary endpoint is the change in dose steps of the minimum daily ICS dose required to ensure asthma control according to the ACQ6 (ACQ6 score = 1.0) between baseline and after AIT. The ICS dose will be determined by means of diary entries as described in Section 5.1.

Timepoint(s) of evaluation of this end point: after the end of the trial

Secondary Outcome(s)

Secondary end point(s): The following secondary endpoints will be assessed:
Efficacy
“Change” refers to the change between the baseline value and the value after AIT.
• Response status in terms of improvement by at least one dose step of the minimum daily ICS dose required to ensure asthma control between baseline and after AIT
• Response status in terms of no need for ICS after AIT
• Change of the minimum daily ICS dose (Budesonide) in µg required to ensure asthma control.
• Change in ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline according to the ACQ6.
• Change in severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline
• Change in use of bronchodilator rescue medication (Salbutamol) with the daily ICS highest dose the patient was not controlled at baseline
• Change in pre-bronchodilator morning peak flow with the highest daily ICS dose the patient was not controlled at baseline
• Change in the number of night time awakening with the highest daily ICS dose the patient was not controlled at baseline
• Change in limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline
• Change in the number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline
• Change in the outcome of the Quality of Life Questionnaire (Mini-AQLQ) with the highest daily ICS dose the patient was not controlled at baseline
• Change in patient’s FEV1 value with the highest daily dose ICS the patient was not controlled at baseline
• Change of the Combined Symptom (rhinitis symptoms) and Medication Score (CSMS) under the lowest daily ICS dose required to ensure asthma control at baseline
• Change of the Combined Symptom (rhinitis- and conjunctivitis symptoms) and Medication Score (CSMS) under the lowest daily ICS dose required to ensure asthma control at baseline
• Change of rhinitis symptoms of the CSMS under the lowest daily ICS dose required to ensure asthma control at baseline
• Change of the rhinitis medication score of the CSMS under the lowest daily ICS dose required to ensure asthma control at baseline
• Change of IgG4
• Change of eosinophils
• The time until the first moderate or severe asthma exacerbation during the diary phase after AIT
• The time until the first moderate or severe asthma exacerbation from the time of first injection until the end of trial.
• The number of asthma exacerbations (moderate or severe) during the diary phase after AIT.
• The number of asthma exacerbations (moderate or severe) from the time of first injection until the end of trial.
• Number of severe asthma exacerbations during the diary phase after AIT
The number of severe asthma exacerbations from the time of first injection until the end of trial.
• Number of moderate asthma exacerbations during the diary phase after AIT
• The number of moderate asthma exacerbations from the time of first injection until the end of trial.
Safety
In addition to the efficacy endpoints, the safety of the treatment during the entire trial period will be assessed by
• Adverse events
• Clinical laboratory tests (hematology, clinical chemistry, and urinalysis)
• Vital signs (resting blood pressure, pulse rate, and respiratory rate)
• An assessment of the overall tolerability by the investigator and the patient using a 5 point Likert scale (Likert, 1932)

Timepoint(s) of evaluation of this end point: After the end of the trial

Secondary ID(s)

AL1402ac

2015-000188-15-PL

Source(s) of Monetary Support

Allergopharma GmbH & Co. KG

Ethics review

Status: Approved
Approval date:
Contact: