Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Grass Pollen Allergy Vaccine

Inclusion Criteria:

• Patients had a positive skin prick test for grass and rye allergen (wheal >= 5 mm greater than the negative control)
• Patients had a positive skin prick test to positive histamine control with a wheal (longest) diameter >= 3 mm.
• Patients had a negative skin prick test to negative control; redness, but no wheal was acceptable.
• Specific IgE for grass and rye as documented by radioallergosorbent (RAST) or equivalent test with class >= 2
• History of at least 1 season of moderate to severe seasonal rhinoconjunctivitis due to an IgE-mediated allergy to pollen from grass and rye
• Patients scored moderate or severe in the disease severity questionnaire

• Males or non-pregnant, non-lactating females who are post-menopausal or naturally or surgically sterile (hysterectomy; bilateral oophorectomy; bilateral tubal ligation with surgery at least 6 weeks prior to study initiation). Postmenopausal was defined as at least 12 months natural spontaneous amenorrhea, or at least 6 weeks following surgical menopause (bilateral oophorectomy). Females of childbearing potential were required to have a confirmed absence of pregnancy according to a negative urine pregnancy test and were required to be using one of the following acceptable birth control methods:

  1. Intrauterine device (IUD) in place for at least 90 days
  2. Barrier method (condom or diaphragm) with spermicide
  3. Stable hormonal contraceptive for at least 90 days prior to study and through study completion
  4. Abstinence
  5. Non-heterosexual lifestyle
  6. Vasectomised partner for at least 90 days.
• Patients were normally active and otherwise judged to be in good health on the basis of medical history, physical examination, and routine laboratory tests.
• Patients were willing and able to attend required study visits.
• Patients were able to follow instructions.
• Patients were willing and able to give written informed consent and provided this consent. Consent was required prior to the initiation of any washout period.
• Spirometry at Screening demonstrates FEV1>= 80% predicted and FEV1/FVC>= 70%.

Exclusion Criteria:

• Acute or subacute atopic dermatitis and/or urticaria factitia and/or urticaria due to physical or chemical influence and/or chronic dermatitis
• Patient has moderate to severe asthma. Patients with mild asthma requiring use of bronchodilators as needed were allowed as long as they did not have significant worsening with seasonal exposure to grass pollen
• Visual inspection of the forearms indicates potential problems with the conduct or interpretation of the skin prick test; both forearms must be available for testing
• History or presence of diabetes (insulin dependent and non-dependent), cancer or any clinically significant cardiac, metabolic renal, hematologic diseases or disorders
• Recent clinically significant history (within 2 years) of hepatic gastrointestinal, dermatologic, venereal, neurologic or psychiatric diseases or disorders
• Any clinically significant (as determined by the investigator) abnormal laboratory value at Visit 0
• Clinically relevant sensitivity to any of the following perennial allergens: house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), molds (Cladosporium cladosporoides, Alternaria alternata, Penicillium chrysogenum, Aspergillus fumigatus) and epithelia (cat [Felis domesticus], dog [Canis familiaris])
• Patient had clinically relevant sensitivity determined by a positive case history, skin prick test wheal size >= 3 mm in diameter greater than the negative control, or RAST test with class >= 2 against the following summer/autumn season flowering plants: Plantago lanceolata (plantain), Atriplex sp. (orache), Urtica dioica (nettle), Artemisia vulgaris (mugwort), Cynodon dactylon (Bermuda grass), or Ambrosia elatior (ragweed).
• Secondary alteration at the affected organ (i.e. emphysema, bronchiectasis)
• History of autoimmune diseases and/or rheumatoid diseases
• Patients who are taking b-blockers for any indication
• Patients who are not allowed to receive adrenalin
• Disorder of tyrosine metabolism (especially in the case of alcaptonuria, tyrosinemia).
• Presence of a disease with a pathogenesis interfering with the immune response and had received medication which could influence the results of this study
• Documented evidence of acute or significant chronic infection
• History of anaphylaxis, including anaphylactic food allergy, insect venom anaphylaxis, or exercise- or drug-induced anaphylaxis.
• Documented history of angioedema
• Hypersensitivity to the excipients in the study medication
• Previous or current hyposensitization therapy with comparable grass allergen extracts
• Currently using anti-allergy medication and other drugs with antihistaminic activity
• Currently participating in a clinical trial or has been exposed to study drug within the last 30 days
• Could not communicate reliably with the Investigator or was not likely to cooperate with the requirements of the study
• Patient is pregnant or planning pregnancy and/or lactating
• Patient has received treatment with preparation containing monophosphoryl lipid A (MPL) during the past 12 months.
• Concurrent use of any prohibited medication or inadequate washout of any medication
• Any systemic disorder that could have interfered with the evaluation of the study drug.
• Clinical history (within 2 years) of drug or alcohol abuse, at the Investigator's discretion, that would interfere with the patient's participation in the study.
• Study site staff or immediate relatives of study site staff or other individuals who would have access to the clinical study protocol