Safety, Immunological Effect and Efficacy of the Combined Application of MPL and Grass Pollen Allergen

Inclusion Criteria:

• Male or female subjects, between 18 and 65 years.
• BMI 18 - 32 kg/m².
• Positive skin prick test (wheal>4mm) with grasses pollen allergen extract.
• Specific IgE to grass pollen allergens by RAST (or equivalent test) ≥ class 2.
• Women of childbearing potential must be using a medically acceptable method of birth control and have a negative β-HCG pregnancy test result at screening and Day 1 predose. Male subjects must also agree to use the double barrier method of contraception during the study.
• In the opinion of the investigator, each subject will be able to understand verbal and written instructions and competent to follow these instructions.
• Subjects must read, understand, sign, and date the written informed consent form

Exclusion Criteria:

• Positive human immunodeficiency virus (HIV)-test, acute or chronic hepatitis B/C (except vaccination titer).
• Positive drug screen.
• Positive alcohol breath test.
• Known or suspected drug or alcohol abuse.
• History of clinically significant cardiovascular (especially heart failure or pulmonary insufficiency), pulmonary (except for asthma), hepatic, renal, gastrointestinal, hematologic, endocrine, dermatological, or metabolic disease within the last 2 years. A clinically significant disease is defined as a disease which, in the opinion of the investigator, may either put the subject at risk because of participation in the trial or a disease which may influence the results of the trial or the subject's eligibility to participate in the trial.
• Clinically significant abnormalities on pre-study physical examination, vital signs, electrocardiogram (ECG), or laboratory tests; acute illness within 7 days before the screening visit.
• History of allergy to all-season allergens and / or history of allergy to other seasonal allergens than grass pollen which might interfere with period of trial conduct
• History of a major psychiatric disorder such as schizophrenia, other psychotic symptomatology, major depressive disorder, or suicide attempt within the past 5 years; history of alcohol or drug abuse within the past year; history or evidence of a progressive central nervous system (CNS) disease, lesion, or encephalopathy.
• History of malignancy within the past 2 years; with the exception of basal cell carcinoma.
• Acute or subacute atopic dermatitis.
• Periodontitis, gingivitis, gingival bleeding or other mucosal disorders in the oral cavity or planned tooth extraction during the course of the study.
• Secondary changes of the reactive organs (e.g., emphysema, bronchiectasis).
• Auto-immune disease (e.g., of liver, kidney, thyroid, nervous system) rheumatoid diseases.
• Immunodeficiencies (e.g., by immunosuppressive agents).
• Therapy with β-blockers.
• Therapy with antihistamines less than three days prior to Day 1 .
• Therapy with corticosteroids (except hormonal contraceptives) four weeks prior to Day 1 (with the exception of local steroids, which must be terminated from three days prior to Day 1).
• Vaccinations in the last three months.
• Unable to comply with recommended therapy-free interval for specified medications prior to skin prick test.
• Current diseases with a pathogenesis interfering with the immune response and diseases for which medication has been given, which could influence the results of this study.
• Acute or chronic infection.
• Already undergone hyposensitization therapy with grass pollen allergens within the last three years.
• Use of MPL-containing products within the last 12 months or allergy / hypersensitivity to MPL.
• Pregnancy or breast-feeding.
• Use of any investigational drug or medical device within 30 days prior to the screening visit.
• A handicap that would prevent compliance with the study procedures or proper reporting of adverse events.
• Subjects who smoke more than 10 cigarettes a day
• Subjects unable to conduct nasal washes and comply with nasal challenge tests according to the instruction of the investigator
• Total flow during rhinomanometry with vehicle solution is more than 40% lower than total flow obtained with blank measurement (note: this exclusion criteria does not apply to the screening visit but to nasal challenge test performed on Day 1 predose)
• In the opinion of the investigator, unable to complete the study.