Safety and Efficacy of Specific Immunotherapy With an Aluminium Hydroxide-adsorbed Allergoid Preparation of Birch Pollen Allergens

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Allergopharma GmbH & Co. KG
ClinicalTrials.gov Identifier:
NCT00263627
First received: December 8, 2005
Last updated: July 2, 2014
Last verified: November 2013
  Purpose

The aim of this clinical trial is to show safety and efficacy of the allergoid preparation of birch pollen allergens in the treatment of birch allergic patients in a representative number of patients.


Condition Intervention Phase
Pollen Allergy
Biological: Birch pollen allergoid
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre Randomised Placebo-controlled Double-blind Clinical Trial for Evaluation of Safety and Efficacy of Specific Immunotherapy With an Aluminium Hydroxide-adsorbed Allergoid Preparation of Birch Pollen Allergens

Resource links provided by NLM:


Further study details as provided by Allergopharma GmbH & Co. KG:

Primary Outcome Measures:
  • Symptom Medication Score (SMS) [ Time Frame: over a period of eight to twelve weeks during the two pollen seasons in ] [ Designated as safety issue: No ]
    The primary endpoint was the area under the curve (AUC) of the daily sum of the Symptom Medication Score (SMS) after two years of double-blind treatment. Each patient recorded the information used for deriving the SMS over a period of eight to twelve weeks during the two double-blind pollen seasons in 2006 and 2007.


Secondary Outcome Measures:
  • Adverse events (AEs) [ Time Frame: Entrire study period. ] [ Designated as safety issue: Yes ]
    Safety: (all five years of treatment) occurrence of adverse events (AEs).


Other Outcome Measures:
  • Well days [ Time Frame: Entire diary period ] [ Designated as safety issue: No ]
    Number of "well days" (Symptom Score ≤ 4, Medication Score = 0)


Enrollment: 253
Study Start Date: June 2005
Study Completion Date: March 2010
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Sterile aluminium hydroxide suspension for subcutaneous injection were applied in the upper arm. Vials with strength A contained 0.0125 mg/mL and with strength B 0.125 mg/mL histamine-dihydrochloride and strength 0 was produced by dilution of strength A. The vials containing the placebo solution were identical in their outer appearance with the active study preparation of the birch pollen allergoids.
Other: Placebo
Sterile aluminium hydroxide suspension for subcutaneous injection were applied in the upper arm. Vials with strength A contained 0.0125 mg/mL and with strength B 0.125 mg/mL histamine-dihydrochloride and strength 0 was produced by dilution of strength A. The vials containing the placebo solution were identical in their outer appearance with the active study preparation of the birch pollen allergoids.
Other Name: Comparator
Experimental: Specific Immunotherapy
Subcutaneous injections with birch pollen allergoid were applied in the upper arm. Vials with three different concentrations were used: Strength A (1000 TU/mL), strength B (10 000 TU/mL) and strength 0 (100 TU/mL) by dilution of strength A.
Biological: Birch pollen allergoid
Subcutaneous injections were applied in the upper arm. Vials with three different concentrations were used: Strength A (1000 TU/mL), strength B (10 000 TU/mL) and strength 0 (100 TU/mL) by dilution of strength A.
Other Name: specific immunotherapy

Detailed Description:

Type I allergy is an immune-disorder which stems from the formation of IgE antibodies against proteins and glycoproteins from plants, insects, animals and fungi, most of which for healthy subjects are considered to be harmless. However, in allergic patients the cross-linking of specific IgE-antibodies on effector cells by allergens activates an immunological cascade leading to the symptoms of Type I allergy including rhinitis, conjunctivitis, asthma, and anaphylactic shock. Pollens from wind-pollinated plants including trees, grasses and weeds, are amongst the most frequent and potent elicitors of Type I allergy. It is not possible to avoid exposure to these pollens and therefore the symptoms that patients inevitably suffer must be treated with either symptomatic medication or allergen specific immunotherapy.

The Betulaceae family includes the genera Alnus (alder), Betula (birch) and Corylus (hazel). Trees belonging to these genera are widespread in middle and northern Europe and, in combination with the fact that they shed large quantities of wind-borne pollen, leads to their allergenic significance. The prevalence of sensitisation to birch pollen has been studied, and in the case of a middle European (Viennese) population, for example, it has been demonstrated that approximately 40 % of patients with allergic rhinitis are sensitised. Although the pollen season for any one genera seldom lasts for more than a few weeks, the well-documented cross-reactivity between the different Betulaceae and other tree pollens of the Fagales order contributes to a protracted season of symptoms for many allergic patients.

Allergoids are prepared by chemical modification of partially purified native aqueous aller-gen extracts. Native allergen extracts are depleted of components with a molecular mass of less than 5000 Dalton by diafiltration prior to chemical modification with aldehydes. The modification causes a substantial reduction in the allergenicity of the extract as can be judged by skin prick testing, provocation testing, histamine release from sensitised leukocytes and measurement of IgE-binding activity by RAST-inhibition. However, immunogenic activity and T-cell reactivity are retained. These properties enable allergoids to be used as a basis for allergen specific immunotherapy with a reduced risk of inducing IgE-mediated side-reactions and the possibility of administering larger doses of immunogen over a shorter time course than with native allergens.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Rhinitis
  • Rhinoconjunctivitis
  • Positive skin prick test to birch pollen
  • Positive radioallergosorbent test (RAST) to birch pollen
  • Positive provocation test result to birch pollen

Exclusion Criteria:

  • Serious chronic diseases
  • Other perennial allergies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00263627

Locations
Germany
Allergopharma Joachim Ganzer KG
Reinbek, Germany, 21465
Sponsors and Collaborators
Allergopharma GmbH & Co. KG
Investigators
Principal Investigator: Annemie Narkus, M.D.
  More Information

Additional Information:
No publications provided

Responsible Party: Allergopharma GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT00263627     History of Changes
Other Study ID Numbers: Al0204AV, 2005-000025-35
Study First Received: December 8, 2005
Last Updated: July 2, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Allergopharma GmbH & Co. KG:
specific immunotherapy
birch pollen allergy
Allergovit

Additional relevant MeSH terms:
Rhinitis, Allergic, Seasonal
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Nose Diseases
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Respiratory Tract Diseases
Rhinitis
Aluminum Hydroxide
Histamine
Histamine phosphate
Adjuvants, Immunologic
Antacids
Histamine Agents
Histamine Agonists
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 30, 2014