Allergic asthma
Conditions
Interventions
Trade Name: ACARIZAX
Product Name: ACARIZAX
Pharmaceutical Form: Oral lyophilisate
Pharmaceutical form of the placebo: Oral lyophilisate
Route of administration of the placebo: Sublingual use
Sponsors
None listed
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Written informed consent Age >18 through 25 ppb at V0 Blood eosinophils > 0,3 x 109/L Sputum eosinophils > 3% A FEV1value of = 70% at V0 ACQ-6 > 1 (partly controlled) at V0 A stable asthma controller regimen with ICS (±LABA) for at least 4 weeks prior to V0 Sensitisation to HDM defined by =1 of following: Positive skin prick test for either: Dermatophagoides pteronyssinus or Dermatophagoides farina IgEHDM > 0.7 x103IU/L Subjects must demonstrate acceptable inhaler and spirometry techniques during screening (as evaluated and in the opinion of study site staff) 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 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Any of the following would exclude the subject from participation in the study: 1. Oral corticosteroids (any dose for more than 3 days) 8 weeks prior to V1 and during run-in. 2. Acute upper or lower respiratory infections requiring antibiotics or antiviral medications 6 weeks prior to V0 and during run-in. 3. Severe oral conditions such as but not limited to: Oral ulcers Oral lichen planus Oral mycosis 4. Current smokers 5. Any of the following concomitant allergies: Birch, Cat, Dog, Horse Ever in treatment with any AIT 7. Previous medical history or evidence of an uncontrolled intercurrent illness that in the opinion of the investigator may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject’s ability to participate in the study. Subjects with well-controlled comorbid disease (eg, hypertension, hyperlipidaemia, gastroesophageal reflux disease) on a stable treatment regimen for 15 days prior to Visit 0 are eligible. Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (eg, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, bronchiectasis, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, alpha-1-antitrypsin deficiency, Wegeners granulomatosis, Sarcoidosis). Any clinically relevant abnormal findings in haematology or clinical chemistry (laboratory results from Visit 1), physical examination, vital signs during the screening, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject’s ability to participate in the study. Evidence of active liver disease, including jaundice, alanine transaminase, bilirubin, greater than twice the upper limit of normal (laboratory results from Visit 0). History of cancer: a. Subjects who have had basal cell carcinoma or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to Visit 1. b. Subjects who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to Visit 1. A helminth parasitic infection diagnosed within 24 weeks of Visit 1 that has not been treated or has not responded to standard of care therapy. Known history of active tuberculosis (TB). Subjectsmay be enrolled if they have ALL of the following: No symptoms of TB: productive, prolonged cough (> 3 weeks); coughing up blood; fever; night sweats; unexplained appetite loss; unintentional weight loss. No known exposure to a case of active TB after most recent prophylaxis (prophylaxis required only if positive). No evidence of active TB on chest radiograph within 3 months prior to the first dose of investigational product. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol. A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject’s verbal report. History of any known primary immunodeficien
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effects of allergen immunotherapy on anti-viral immunity in patients with allergic asthma. Main outcome is to investigate potentiale change in bronchial epithelial cells interferon secretion before and after 6 month of treatment with ACARIZAX or placebo. ;Secondary Objective: To investigate the effect of allergen immunotherapy on anti-bacterial response in patients with allergic asthma. To investigate the potential change in immunologic phenotype in BAL-fluid. To investigate the potential change in cell supernatants for epithelial derived Th1/Th2 cytokines aswell as th1/th2 (anti)-inflammatory cytokines. To investigate the potential change in histologic phenotype in bronchial biopsies To investigate the potential change in airway inflammation markers in sputum. ;Primary end point(s): Change in interferon-B gene / and or protein expression Cahnge in interferon-gamma gene/and or protein expression Change in viral load and/or TCID50 assay;Timepoint(s) of evaluation of this end point: Bronchoscopy at V2 and V7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in: - IFN-ß mRNA expression - IFN-? mRNA expression Anti-bacterial measures: - IL-12 - ß-defensin - IFN- ? - Th1/Th2 balance - NK-cells - CD8+ T-cells. - Treg-cells, Breg-cells - Inflammatory cytokines such as but not restricted to: IL-4, IL-5, IL-13, IL-33, IL-25, IL-ß and TSLP - Anti-inflammatory cytokines such as but not restricted to: IL-10, TGF-ß - IL-4, IL-5, IL-13, IL-33, IL-25, IL-ß and TSLP - IL-10, TGF-ß - IFN-ß/TSLP ratio. Number / percentage of eosinophils and neutrophils in airway submucosa, sputum and blood. Cell count of following types: - Mast cells - Eosinophils - Neutrophils - pDC’s ;Timepoint(s) of evaluation of this end point: Bronchoscopy at V2 and V7 Sputum at: V1 and V6. | — |
Countries
Denmark
Outcome results
None listed