Double-blind Randomized Parallel Group Study of 3 Cumulative Doses of Grass MATA MPL Compared to Placebo and Grass MATA in Patients With Seasonal Allergic Rhinoconjunctivitis Exposed to Grass Pollen in mEECs™ Out of the Grass Pollen Season
Double-blind Randomized Parallel Group Study of 3 Cumulative Doses of Grass MATA MPL Compared to Placebo and Grass MATA in Patients With Seasonal Allergic Rhinoconjunctivitis Exposed to Grass Pollen in mEECs™ Out of the Grass Pollen Season
There is increasing evidence that the effectiveness of allergy immunotherapy to control symptoms of rhinoconjunctivitis is related to the cumulative dose of allergen or allergoid administered during a single regimen of subcutaneous (SC) injections or of sublingual administration. The current therapeutic dose regimen for Grass MATA MPL is a course of four injections of 300, 800, 2000 and 2000 SU (Standardized Units), administered at weekly intervals (cumulative dose 5100 SU). Two new cumulative doses of the Grass MATA MPL 10200 SU and 18200 SU are being developed to compare with the current dose. The study is designed to explore the benefit/risk of increasing the cumulative allergen dose of the Grass MATA MPL immunotherapy comparing these doses with the current dose of Grass MATA MPL, Grass MATA (without MPL) and placebo.
This study will be conducted outside the grass pollen season and is comprised of five periods.
Period 1 is the screening visit (Visit 1), and will occur 3 to 28 days before Visit 2.
Period 2 includes the pre-randomization, grass pollen exposure visits, which consist of four 3 hour sessions in the mEEC™ (Visits 2, 3, 4 and 5) during which patients will be exposed to grass pollen and record nasal and non nasal symptoms using electronic diaries (electronic Patient Data Acquisition Tablet: ePDAT™) prior to entry and every 30 minutes post entry into the mEEC™. Patients will attend mEEC™ visits on consecutive days. To be eligible for randomization and proceed to Treatment (Period 3), patients must achieve the following by the final pre treatment mEEC™ (Visit 5):
Period 3 includes the six treatment visits (Visit 6, 7, 8, 9, 10 and 11). After each injection, patients will be kept under observation by personnel qualified to manage systemic allergic reactions at the site for at least 30 minutes. This period can be extended by the investigator in response to injection site or systemic allergic reactions. The observation will be followed up by a telephone call approximately 24 hours later.
Period 4 consists of four 3 hour sessions (Visits 12, 13, 14 and 15) in the mEEC™ during which patients will be exposed to grass pollen and record post-treatment TSS using the ePDAT™ as in Period 2.
Period 5 consists of an End of Study (EOS) safety follow-up visit (Visit 16) between 2 and 14 days after the last EEC visit. A telephone follow-up will be made at approximately 3, 6, and 12 months following the last injection with detailed enquiry with regard to expected and non-expected AEs, with special attention to New Onset Autoimmune Disorders (NOAD) and Neuro-inflammatory (NI) disease. For subjects who withdraw early, similar follow up will be done at approximately 1, 3, 6, and 12 months following the last injection.
Inclusion Criteria:
Aged 18 to 50 years inclusive
Allergy to grass pollen allergen, defined by:
Positive skin prick test to histamine (wheal (longest diameter) ≥ 3 mm greater than the negative control)
Negative skin prick test to the negative control (redness with wheal ≤ 2 mm is acceptable)
For asthmatic patients: Forced expiratory volume (FEV) in 1 second (FEV1) ≥ 80% of National Health and Nutrition Examination Surveys (NHANES) predicted, with a FEV1/Forced Vital Capacity (FVC) ratio ≥ 70%
Obtain the minimum qualifying symptom scores by the final pre treatment EEC visit to be enrolled into the study. Minimum qualifying TSS is at least 12 out of a possible 24 on at least one recording time, a TNSS score of at least 7 out of a possible 12 on at least one recording time, and a rhinorrhea score of at least 2 on at least two diary cards.
Observe the drug washout times for antihistamines, steroids etc. as specified in the protocol prior to screening (Visit 1). The use of other medications will be permitted if they are not expected to interfere with the ability of the patient to participate in the study and provided they have been on a stable regimen (i.e., the same dosage and administration) for six weeks prior to screening
Males or non pregnant, non lactating females who are:
i. Stable hormonal contraceptive for ≥ 90 days prior to Visit 1 and for at least 7 days after the final injection. If < 90 days prior to the study, additional use of a double barrier method until 90 days reached is required.
ii. Placement of an intrauterine device (IUD) or intrauterine system iii. Use of barrier methods of contraception (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream/suppository iv. Use of double barrier methods of contraception (e.g., male condom with diaphragm, male condom with cervical cap) v. Male sterilization with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate of the sole partner vi. True abstinence, when in line with the preferred and usual lifestyle of the patient; periodic abstinence, such as calendar, ovulation, symptothermal, post ovulation methods, and withdrawal are not acceptable methods of contraception.
Normally active and otherwise judged to be in good health on the basis of medical history, physical examination and routine laboratory tests.
Willing and able to give written informed consent.
Able to understand and comply with study instructions.
Willing and able to attend required study visits.
Exclusion Criteria:
In the presence of symptoms outside the grass pollen season coupled with a positive skin test to a perennial allergen, if as assessed by the Investigator the patient is unable to avoid the offending allergen.
Concurrent disease that might complicate or interfere with investigation or evaluation of the study medications or the skin prick test result, such as:
Emergency room visit or admission for asthma in the 12 months prior to Visit 1 or history of a life-threatening asthma attack ever
Presence of acute or subacute atopic dermatitis, chronic dermatitis, urticaria factitia, or urticaria due to physical/chemical influence
Presence of secondary alterations at the affected organ (i.e., emphysema, and bronchiectasis )
Current diagnosis of Type I diabetes. Patients with Type II diabetes will only be allowed to participate at the discretion of the Investigator
Autoimmune disease (e.g., of liver, kidney, lung, thyroid, nervous system, rheumatoid diseases) sarcoidosis, or NI disease (e.g., optic neuritis, multiple sclerosis or other demyelinating disease, encephalitis or encephalomyelitis, myelitis/transverse myelitis, myasthenia gravis, Guillain Barré syndrome, unexplained transitory neurological events)
History of cancer (excluding basal cell carcinoma) or concomitant illness (e.g., cardiovascular, pulmonary, metabolic, renal, hepatic, gastrointestinal, dermatologic, venereal, hematologic, neurologic, or psychiatric diseases or disorders) that, in the opinion of the Investigator, would pose a safety risk or compromise the interpretation of efficacy for this grass immunotherapy
Use of oral, intramuscular, intravenous corticosteroids, or potent or super-potent topical corticosteroids, from 30 days prior to screening up to Visit 16
Any systemic disorder that could interfere with the evaluation of the study medications
Presence of tattoos or other skin abnormalities in the upper arms which would prevent an accurate assessment of local skin reaction, at Investigator's discretion
Clinical history of allergy, hypersensitivity or intolerance to the excipients of the study medication
Active or quiescent tuberculous infection of the respiratory tract, untreated local or systemic fungal or bacterial or systemic viral infections (e.g., chickenpox or measles) or parasitic or ocular herpes simplex
Experience of nasal septal ulcers, nasal surgery or nasal trauma within 90 days of Visit 1
Clinical history of anaphylactic reactions to foods, insect venom, exercise, drugs or idiopathic anaphylaxis
Clinical history of immunodeficiency, including those who are on immunosuppressant therapy
Diseases with a pathogenesis interfering with the immune response and who have received medication which could influence the results of the study
Clinical history of recurrent idiopathic angioedema
Tyrosine metabolism disorders, especially tyrosinemia and alkaptonuria
β blocker medication, including eye drops, for any indication
Monoamine Oxidase Inhibitor medication
Unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicated)
Clinical history of drug or alcohol abuse which would, at the Investigator's discretion, interfere with the patient's participation in the study
Clinical history, or evidence, of nasolacrimal drainage system malfunction
Any clinically significant abnormal laboratory value (as determined by the Investigator) at Visit 1
Study site staff or immediate relatives of study site staff or other individuals who would have access to the clinical study protocol or people considered as vulnerable or institutionalized
Have undergone specific immunotherapy with comparable allergen extracts. An exception will be allowed if prior immunotherapy with comparable allergen was successful, symptoms reappeared sometime after stopping the immunotherapy, and the immunotherapy was completed ≥ 3 years before Visit 1
Treatment with a preparation containing MPL® within 6 months prior to Visit 1
Participation in a clinical research study with an investigational medicinal product within 4 weeks of Visit 1 or concomitantly with this study, including the safety follow-up period up to 12 months following the last injection.