A multicentre multinational randomised, placebo-controlled, double-blind pivotal trial for the evaluation of safety and efficacy of specific immunotherapy with a cocktail of recombinant major allergens of Timothy Grass Pollen (Phleum pratense) adsorbed onto aluminium-hydroxide in patients with IgE-mediated allergic rhinoconjunctivitis with/without controlled asthma (AMETHYST) - (AMETHYST)

• Conditions: ICD classification code: J45.0 and J 30.1; MedDRA version: 14.0Level: LLTClassification code 10001728Term: Allergic rhinoconjunctivitisSystem Organ Class: 10015919 - Eye disorders; MedDRA version: 14.0Level: LLTClassification code 10001705Term: Allergic asthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2007-003208-37-DE
• Lead Sponsor: Allergopharma Joachim Ganzer KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09-24
• Last Update Posted: 21 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 750

Inclusion Criteria

-Written Informed Consent
- Male and female outpatients, 18-60 years legally competent
- Patients suffering from IgE-mediated, moderate to severe seasonal allergic
rhinitis with or without controlled bronchial asthma (PEF and/or FEV1 at least
80% predicted normal) attributable to grass pollen
- In the course of the year: Major allergy symptoms during grass pollen season
- Symptoms of allergic rhinoconjunctivitis against grass pollen allergens requiring
medication during the last grass pollen season
- Proven clinical relevance of grass pollen allergy by positive conjunctival
provocation test (CPT) result using natural grass pollen cocktail.
- Positive skin prick test reaction to natural grass pollen allergens demonstsrated by
grass pollen allergen weal diameter >= 5mm (to be demonsstrated in a valid skin
prick test: Negative NaCl control weal < 3 mm, positive Histamine (o.1%)L control
weal >= 3 mm)
- Positive EAST to grass pollen >= 1.5 kU/l to be determined in central laboratory
- For female patients: effective contracetption and negative pregnancy test result.
Highly effective methods of birth control are defined as those which result in a low
failure rate (i.e. less than 1% per year) when used consistently and correctly such
as implants, injectibles, combined or oral contraceptives, some IUDs, sexual
abstinence or vasectomised partner. No pharmacological interactins are known for
hormonal contraceptives and specific immunotherapeutic preparations.

At the Beginning of the Treatment Phase (November 2009):
Patients must have demonstrated moderate to severe symptoms of allergic grass pollen disease during the baseline season. Details are described in section 10.1.1 of Trial Protocol
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Previous course of hyposensitisation against grass pollen or unknown other
allergens in any pharmaceutical form
- Patients who have undergone an unsuccessful course of specific immunotherapy
with any allergen
- For allergens which interfere with the grass pollen season during May to August
(Plantain, Nettle, Cypressus where appropriate, Olive tree, Parietaria officinalis, Alternaria alternata, Cat
epithelia, Dermatophagoides farinae, Dermatophagoides pteronyssinus):
sensitisation in the Skin Prick Test:
° Weal diameter of respective interfering allergen >= weal diameter of grass pollen
allergen
° Sensitisation as determined by serum EAST > 1,5 kU/l
- Clinical.y relevant sensitisation has to be excluded in a provocation test
- Clinically relevant rhinoconjunctival or respiratory symptoms related to other
reasons than allergy
- PEF or FEV1 < 80% of predicted normal (ECCS) or uncontrolled/partly controlled
bronchial asthma according to the GINA Guidelines (2006)
- Febrile infections or inflammation of the respiratory tract at the time of inclusion
- Irreversible secondary alternations of the reactive organ (emphysema,
bronchiectasis etc.)
- Severe acute or chronic diseases, severe inflammatory diseases
- Other severe generalised diseases (liver, kidneys, metabolic diseases)
- Autoimmune diseases, immune defects including immuno-suppression, immune-
complex-induced immunopathies
- Severe psychiatric and psychological disorders including impairment of cooperation
(i.g. alcohol or drug abuse)
- Completed or ongoing long-term treatment with tranquillizer psycho active drug

Allergy treatment according to severity of symptoms with other than the following medication during the baseline grass pollen season:

° Levocabastine nasal spray/eye drops (0.5 mg/ml each),
° Loratadine/Cetrizine tablets (10 mg), Salbutamol 100 µg/puff), inhaled
steroid in higher doses than 500µg/d Beclomethasonedipropionate/equivalent
Treatment of exacerbation of allergic rhinoconjunctivitis and bronchial asthma with
a short course oforal corticosteroids permitted. Treatment with or other
medication must be stopped 2 weeks prior to start of this study

° Basic asthma treatment with other medication than short acting bronchodilatators and inhaled corticosteroids higher than 500µg Beclomethasonedipropionate or equivalent

Any prophylactic and any treatment with antiallergic medication in fixed (constant) dosage during the baselilne and any grass pollen seasons during the study

- Pregnancy and location period
- Female patients seeking to become pregnant
- Concurrent participation in any other clinical trial or participation in any other clinical
trial during the previous 30 days
- Low compliance or inability to understand instructions / study documents
-Patients committed to a mental hospital by government or court
- completed or ongoing treatment with Anti-EgE antibody
- Patients being in any relationship of dependence with the sponsor and/or
investigator
- Contraindication for adrenaline, (e.g. acute or chronic symptomatic coronary heart
disease, severe arterial hypertension)
- Treatment with beta-Blockers, locally and systemically

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified