subcutaneous immunotherapy in allergic rhinits (AR) patients with allergies to birchpollen
Conditions
Sponsors
Academic Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for study subjects: 1. Signed informed consent 2. Age =18 = 60 years 3. Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests. 4. A positive SPT (mean wheal diameter = 3mm compared to negative control and negative control should be negative) for birch pollen assessed within 1 year before randomization OR a positive serum specific anti-birch IgE-test (>0.7 U/ml) In order to be eligible to participate in this study as a gender, age and location matched healthy control, a subject must meet all of the following criteria: 1. Signed informed consent 2. Age, gender and location matched to a study subject. An age matched control is defined as the age of the study subject ± 5 years. 3. No history of respiratory allergies and no nasal symptoms at screening. 4. A negative SPT (a positive outcome is defined as a mean wheal diameter = 3mm compared to negative control and negative control should be negative) assessed within 1 year before randomization OR a negative serum specific IgE test for aeroallergens. 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 48 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. A history of allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) within the 5 years before inclusion/screening visit 2. Treatment with parenteral Vitamin D3 analogue in the year before inclusion 3. Significant, ongoing nasal symptoms caused by other allergens at study onset 4. A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity 5. Any vaccination within one week before randomization 6. Treatment with experimental products within the last 3 months or during the study or biologicals (including anti-IgE or TNF- a treatment) within the last 6 months or during the study 7. Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs 8. Uncontrolled asthma or other active respiratory diseases 9. Malignancies or any malignant disease during the previous 5 years 10. Severe uncontrolled diseases that could increase the risk for subjects participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or hematological disorders 11. Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study 12. Use of preparations containing calcium or magnesium such as thiazide, diuretics, antacides. 13. Use of systemic steroids within 4 weeks before screening and during the study 14. Daily use of ketoconazole cream or immunosuppressive creams at planned injection site less than 7 days before or during the study 15. Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or –pill) 16. Any clinically significant abnormal laboratory parameter at screening 17. Any physical or mental condition that precludes compliance or participation in a clinical trial 18. Subjects who are employees or students of the institution or 1st grade relatives or partners of the investigators
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate whether 2.5 µg VD3 analogue (Zemplar® – Abbvie) in multiple subcutaneously administered doses induces a more favourable (read: anti-inflammatory) systemic immune modulation both in general parameters and allergen-specific responses in birch pollen allergic subjects more resembling the response observed in gender, age and study site matched healthy control subjects. To this end, the primary outcome of the study is the observed IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at start, at 4 weeks of treatment and follow-up, comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design. The target is a statistically significant increase in IL-10 production upon polyclonal and/or allergen specific stimulation in allergic subjects, more resembling the response expected to be seen in healthy controls.;Secondary Objective: 1) The reactivity, cellular composition and detailed characterization of antigen-presenting cell (APC) and T cells in the PBMC, using proliferation, detailed cell surface marker expression, and cytokine production (beyond IL-10) in response to polyclonal and allergen-specific stimulation. 2) To evaluate the safety and tolerability, both systemically and locally, of the VD3 analogue Zemplar® administered by the subcutaneous route during each treatment visit and at the follow up visit compared to placebo. To evaluate blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function before and after treatment with 2,5 µg VD3 analogue (Zemplar®) in multiple subcutaneously administered doses compared to placebo.;Primary end point(s): The primary outcome of the study is the observed Il-10 production in response to polyclonal and allergen-specific stimulation after 4 weeks of treatment with VD3 analogue Zemplar® compared to placebo.;Timepoint(s) of evaluation of this end point: The immune effects | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Comparison of ?IL-10 between allergic subjects and healthy controls • Cellular composition of PBMC with respect to Th1, Th2, Th17, Th22, and Treg cells, B cells, and antigen-presenting cells (APC) • PBMC proliferation and cytokine production in response to allergen (Bet v 1) • PBMC proliferation and cytokine production in response to polyclonal stimuli (aCD3/aCD28) • Intracellular cytokine measurements in response to PMA/ionomycin • Blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function will be determined at baseline and at the follow up visit. • Safety and tolerability (local and systemic reactions / [serious] adverse events) of the VD3 analogue Zemplar® administered via the subcutaneous route will be evaluated at each treatment visit and the follow up visit. ;Timepoint(s) of evaluation of this end point: Safety measurements and vital signs will be done at each visit. ECG and lungfunction will be done at the randomisation visit and at the follow up visit. urinalysis will be done at screening and follow up. 30 minutes after each injection the injection location will be checked. | — |
Countries
Netherlands
Contacts
Public ContactAMC
Academic Medical Centre
Outcome results
None listed