DBPC-Dose-finding-trial of Vitamin D3 for SCIT in Birch Pollen Allergic Patients.

• Status: Completed
• Trial end date: 2016-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Low Vitamin D3 (VD3) levels have been reported to be associated with the risk of allergic diseases like asthma. VD3 has been demonstrated in vitro, ex vivo and in animal models to program the immune system towards anti-inflammatory immune responses. VD3 co-administered with allergen may be a promising adjuvant to improve the onset and efficacy of allergen immunotherapy (AIT). A clinical trial will be performed to compare the immune effects, the tolerability and safety of multiple doses of aVD3 analogue (registered for the intravenous route) administered by the subcutaneous (s.c.) route in subjects with allergic rhinitis and healthy controls.

The overall aim is to provide additional (in vivo) support for the use of VD3 as an adjuvant in allergen-specific immunotherapy, on top of the existing pre-clinical evidence demonstrating that antigen-presenting cells educate the adaptive immune system towards an anti-inflammatory response when allergen is seen in the presence of VD3.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Laurian Jongejan
• Treatments: Cholecalciferol; Ergocalciferols; Vitamin D; Vitamins

Criteria

Inclusion Criteria (study object):

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)

Inclusion Criteria (healthy control):

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.

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- α 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