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: Screening visit * Period 2: Eligibility and baseline symptom assessments in the mobile environmental exposure chamber (mEEC™) * Period 3: Six treatment visits, during which the study drug will be injected * Period 4: Post-treatment efficacy assessments in the mEEC™ * Period 5: Safety follow-up 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): * Minimum qualifying Total Symptom Score (TSS) of at least 12 out of a possible 24 on at least one exposure using ePDAT™ * Total Nasal Symptom Score (TNSS) of at least 7 out of a possible 12 using ePDAT™ * Runny nose score of at least 2 out of 3 on at least two time points. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
265
Inflamax Research Inc.
Neptune City, New Jersey, United States
Post-treatment TSS
The primary efficacy endpoint will be the mean average of the last three TSS measurements recorded in each of the four post-treatment Visits 12 15. TSS will be measured during the four post-treatment mEEC™ sessions conducted on consecutive days 12-15, and is defined as the sum of individual NSS (rhinorrhea, congestion, sneezing and itchiness) and NNSS (itchy/gritty eyes, tearing/watery eyes, red/burning eyes and ear/palate itching).
Time frame: 21-28 days after the last injection
Frequency of local adverse events (AEs)
A Local AE is located at the injection site of study medication, occurring within 24 hours after the injection.
Time frame: A Local AE is located at the injection site of study medication, occurring within 24 hours after the injection.
Frequency of systemic adverse events (AEs)
A Systemic AE is allergic signs and symptoms (e.g., conjunctivitis, rhinitis, cough and generalized urticaria including anaphylaxis) associated with the injection of study medication, occurring within 24 hours after the injection.
Time frame: 24 hours following each injection
Frequency of other AEs
All post-treatment AEs that do not fall into local or systemic AEs
Time frame: Up to 1 year following injections
Frequency of AEs of special interest (AESI)
AESI includes New Onset Autoimmune Disorders and Neuro-inflammatory events.
Time frame: Up to 1 year following injections
Safety laboratory values
Change in serum chemistry and haematology from baseline to Visit 16
Time frame: Up to 12 weeks
Specific IgE
Change in grass specific IgE from baseline to Visit 16
Time frame: Up to 12 weeks
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