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

NCT02686827 | Completed Phase 2 DMC

• 1 other identifier: BM4SIT
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypersensitivity

Outcome Measures

Primary Outcomes (2)

• change in IL-10 production from baseline

  Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and after 4 weeks of treatment comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.

  baseline and 4 weeks of treatment

• change in IL-10 production from baseline

  Compare the change in IL-10 production as marker of the induction of a more anti-inflammatory systemic immune response, at baseline and at follow-up (between 5-7 weeks) comparing birch pollen allergic subjects and healthy controls in a placebo-controlled design.

  baseline and follow-up visit (between 5-7 weeks)

Secondary Outcomes (64)

• Change in IgE responses to birch pollen compared to baseline

  Baseline compared to 4 weeks of treatment

• To evaluate the number of patients that reported adverse events with Zemplar compared to placebo. This includes adverse measurements in blood safety biochemistry/haematology parameters, urinalysis, vital signs and ECG, lung function compared to placebo.

  Throughout the study and follow-up (a maximum total of 8 weeks)

• changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline

  Baseline compared to 4 weeks of treatment

• changes in percentage Th1 cells characterized by the expression of CD4, CXCR3, CCR6 and T-bet, compared to baseline

  baseline and follow-up visit (between 5-7 weeks)

• changes in percentage Th2 cells characterized by the expression of CD4, CRTh2, CCR4 and Gata-3, compared to baseline

  Baseline compared to 4 weeks of treatment

Study Arms (2)

Paricalcitol (Vitamin D3)

EXPERIMENTAL

paricalcitol, (Zemplar® 5 μg/ml Abbvie), will be administered via the subcutaneous route 4 times at 0.5 ml (registered dose of 5 μg/ml, thus 2.5 μg per sub-cutaneous injection). The minimum time interval between two injections is 4 days, which is a significantly lower frequency than the prescribed maximum of 3 times a week or every other day.

Drug: Paricalcitol

Placebo

ACTIVE COMPARATOR

Placebo, the same constituents as Zemplar (propylene glycol 30% (v/v) alcohol 20% (v/v)) but no paricalcitol, same dosage as verum-arm.

Drug: Placebo (for paricalcitol)

Interventions

Paricalcitol DRUG

Vitamin D3 analogue

Also known as: Vitamin D3, (Zemplar)

Paricalcitol (Vitamin D3)

Placebo (for paricalcitol) DRUG

Injection fluid to mimic paricalcitol injection

Also known as: fluid to mimic paricalcitol injection

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent
• Age ≥18 ≤ 60 years
• Allergic rhinitis/rhino-conjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma based on relative symptoms and allergy tests.
• 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)
• Signed informed consent
• Age, gender and location matched to a study subject. An age matched control is defined as the age of the study subject ±5 years.
• No history of respiratory allergies and no nasal symptoms at screening.
• 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.

You may not qualify if:

• Significant, ongoing nasal symptoms caused by other allergens at study onset
• A history of Hypercalcemia, Hypophosphatemia or vitamin D toxicity
• Any vaccination within one week before randomization
• 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
• Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
• Uncontrolled asthma or other active respiratory diseases
• Malignancies or any malignant disease during the previous 5 years
• 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
• Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
• Use of preparations containing calcium or magnesium such as thiazide, diuretics, antacides.
• Use of systemic steroids within 4 weeks before screening and during the study
• Daily use of ketoconazole cream or immunosuppressive creams at planned injection site less than 7 days before or during the study
• 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)
• Any clinically significant abnormal laboratory parameter at screening
• Any physical or mental condition that precludes compliance or participation in a clinical trial

Sponsors & Collaborators

• Laurian Jongejan: lead

Study Sites (1)

Academic medical center

Amsterdam, 1100 AZ, Netherlands

Location

MeSH Terms

Conditions

Hypersensitivity

Interventions

paricalcitol; Cholecalciferol

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Wytske J Fokkens, Prof MD PhD

  Academic Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Project manager

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 22, 2016
• Study Start: October 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: October 1, 2016
• Last Updated: September 4, 2018

Record last verified: 2018-08

Locations

NL (1)