Allergy, Asthma, Rhinitis
Conditions
Keywords
House Dust Mite
Brief summary
To demonstrate superiority of ALK HDM tablets versus placebo in immune response, measured as change of D.farinae specific immunoglobulin G4 (IgG4) from baseline to end of treatment with ALK HDM tablets given once daily over 60 days.
Detailed description
To demonstrate superiority of ALK HDM tablets versus placebo in the immune response, measured as change of D. Farinae specific IgG4 from baseline to end of treatment with ALK HDM tablets given once daily over 60 days To evaluate the immune response, measured as change of D. pteronyssinus, D. farinae specific immunoglobulin E (IgE) and D. pteronyssinus specific IgG4 from baseline to end of treatment with ALK HDM tablets given once daily over 60 days, compared to placebo To evaluate in patients with HDM-allergic respiratory disease the safety and tolerability of 60-day treatment with ALK HDM tablets compared to placebo
Interventions
DRUGMitizax
Allergen extract
DRUGPlacebo
Placebo tablet
Sponsors
Linical Co., Ltd.
Datamap
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent obtained before entering the study * Patients 18-65 years of age, with a clinical history consistent with HDM-induced allergic rhinitis or allergic rhinoconjunctivitis with or without HDM-induced allergic atopic asthma for more than 1 year * Use of symptomatic treatment of HDM-induced allergic rhinitis and/or HDM-induced atopic asthma, i.e. antihistamines, nasal decongestants, nasal and/or inhaled corticosteroid for more than 1 year * if HDM-induced atopic asthma is present, it should be of mild to moderate severity, controlled on treatment corresponding to steps 1-3 of The Global initiative for asthma (GINA) * Positive skin prick test response (wheal diameter ≥3 mm) to D pteronyssinus and/or D.farinae * Moderate or higher level of D.pteronyssinus and/or D.farinae specific IgE (defined as ≥IgE Class 2; or ≥0.70 kilo unit (kU)/L) * Patient one of the following: 1. Male 2. Female, infertile 3. Female, with a negative pregnancy test and willingness to practice appropriate contraceptive methods until treatment with study drug has been discontinued. * Patient willing and able to comply with study protocol
Exclusion criteria
* Previous treatment with HDM immunotherapy for more than 1 month within the last 5 years * Ongoing treatment with any allergen-specific immunotherapy product * Reduced lung function (defined as Forced expiratory volume in 1 second (FEV1) \< 70% of predicted value after adequate pharmacologic treatment) measured at Visit 1 and Visit 2 * Clinical history of uncontrolled asthma within 3 months prior to the screening visit * Having experienced a severe asthma exacerbation within 3 months prior to screening visit * Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infectious process at randomization * Inflammatory conditions in the oral cavity with severe symptoms such as oral lichen planus with ulcerations or severe oral mycosis at randomization * History of anaphylaxis with cardiorespiratory symptoms (immunotherapy, exercise-induced, food allergy, drugs or an idiopathic reaction) * History of recurrent generalized urticaria (defined as two or more episodes) during the last 2 years * A history of drug induced (incl. immunotherapy) facial angioedema or a family (parents and siblings) history of hereditary angioedema * Any chronic disease (e.g. cystic fibrosis, malignancy, malabsorption or malnutrition, renal or hepatic abnormality or any other diseases that in the opinion of the investigator would interfere with the study evaluations or the safety of the subject) * Systemic disease affecting the immune system (e.g. autoimmune disease, immune complex disease, or immune deficiency disease whether acquired or not) * Immunosuppressive treatment (ATC code L04 or L01) within 3 months prior to the screening visit * Currently treated with tricyclic antidepressants; catecholamine-O-methyltransferase (COMT) inhibitors and mono amine oxidase inhibitors (MAOIs) and beta-blockers including topical administration * Use of medication at the screening visit which at the time of skin prick test (SPT) can interfere with the result (i.e. antihistamines) * Use of an investigational drug within 30 days/5 half-lives of the drug (which ever longest) prior to the screening visit * History of allergy, hypersensitivity or intolerance to a excipient in the investigational medicinal product (except D.Pteronyssinus and D.farinae) * Being immediate family of the investigator or study staff, defined as the investigator's/staff's spouse, parent, child, grandparent or grandchild * Severe mental disorders that in the opinion of the investigator would interfere with the study evaluations or the safety of the subject * Cardiovascular conditions in which complications are possible when using adrenaline * Women who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| D. Farinae Specific IgG4 Change From Baseline to End of Treatment | 60 days from baseline | primary efficacy endpoint of D. Farinae specific IgG4 change from baseline to end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| D. Pteronyssinus Specific IgG4 Change From Baseline to End of Treatment | 60 days from baseline | secondary endpoint of D. pteronyssinus specific IgG4 change from baseline to end of treatment |
| D. Farinae Specific IgE Change From Baseline to End of Treatment | 60 days from baseline | the secondary endpoint of D. farinae specific IgE change from baseline to end of treatment compared to placebo |
| D. Pteronyssinus Specific IgE Change From Baseline to End of Treatment | 60 days from baseline | the secondary endpoint of D. pteronyssinus specific IgE change from baseline to end of treatment compared to placebo |
Countries
Belarus, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mitizax ALK HDM Tablet Standardised allergen extract from the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae developmental unit, dose standard for ALK HDM tablets (12DU)
Mitizax: Allergen extract | 56 |
| Placebo Tablet Placebo tablet
Placebo: Placebo tablet | 56 |
| Total | 112 |
Baseline characteristics
| Characteristic | Mitizax ALK HDM Tablet | Placebo Tablet | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 55 Participants | 108 Participants |
| Age, Continuous | 31.7 years STANDARD_DEVIATION 9.1 | 31.4 years STANDARD_DEVIATION 9.8 | 31.6 years STANDARD_DEVIATION 9.4 |
| Region of Enrollment Belarus | 12 Participants | 12 Participants | 24 Participants |
| Region of Enrollment Russia | 44 Participants | 44 Participants | 88 Participants |
| Sex: Female, Male Female | 27 Participants | 32 Participants | 59 Participants |
| Sex: Female, Male Male | 29 Participants | 24 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 56 | 4 / 56 |
| serious Total, serious adverse events | 0 / 56 | 0 / 56 |
Outcome results
Primary
D. Farinae Specific IgG4 Change From Baseline to End of Treatment
primary efficacy endpoint of D. Farinae specific IgG4 change from baseline to end of treatment
Time frame: 60 days from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mitizax ALK HDM Tablet | D. Farinae Specific IgG4 Change From Baseline to End of Treatment | 0.473 mg antibody/ml | Standard Deviation 1.183 |
| Placebo Tablet | D. Farinae Specific IgG4 Change From Baseline to End of Treatment | -0.01 mg antibody/ml | Standard Deviation 0.067 |
Secondary
D. Farinae Specific IgE Change From Baseline to End of Treatment
the secondary endpoint of D. farinae specific IgE change from baseline to end of treatment compared to placebo
Time frame: 60 days from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mitizax ALK HDM Tablet | D. Farinae Specific IgE Change From Baseline to End of Treatment | 140.37 kUA/L | Standard Deviation 288.15 |
| Placebo Tablet | D. Farinae Specific IgE Change From Baseline to End of Treatment | -5.56 kUA/L | Standard Deviation 16.3 |
Secondary
D. Pteronyssinus Specific IgE Change From Baseline to End of Treatment
the secondary endpoint of D. pteronyssinus specific IgE change from baseline to end of treatment compared to placebo
Time frame: 60 days from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mitizax ALK HDM Tablet | D. Pteronyssinus Specific IgE Change From Baseline to End of Treatment | 124.85 kUA/L | Standard Deviation 286.9 |
| Placebo Tablet | D. Pteronyssinus Specific IgE Change From Baseline to End of Treatment | -5.16 kUA/L | Standard Deviation 27.27 |
Secondary
D. Pteronyssinus Specific IgG4 Change From Baseline to End of Treatment
secondary endpoint of D. pteronyssinus specific IgG4 change from baseline to end of treatment
Time frame: 60 days from baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mitizax ALK HDM Tablet | D. Pteronyssinus Specific IgG4 Change From Baseline to End of Treatment | 0.455 mg antibody/ml | Standard Deviation 1.21 |
| Placebo Tablet | D. Pteronyssinus Specific IgG4 Change From Baseline to End of Treatment | 0.001 mg antibody/ml | Standard Deviation 0.076 |