The purpose of this study is to determine an effective dose range for the administration of ragweed allergenic extract via the sublingual route of administration
Specific allergen immunotherapy as currently practiced in the USA and described in product labeling comprises the subcutaneous injection of incrementally increasing doses to a targeted maintenance dose ("build-up") followed by maintenance injections of allergenic extract/vaccine. Up to 30-40 injections may be required during the build-up phase over a 3-6 month period. When adequate maintenance doses are reached, this form of immunotherapy (SCIT) has been shown to be highly effective and safe. Standard practices recommend that the injections be given under the supervision of trained physicians and that the patient remain in the physician's office at least 20 to 30 minutes after an injection. The administration of immunotherapy injections are not recommended at home because of the risk of inadequate recognition and treatment of systemic reactions. The inconvenience and expense of traveling for allergy injections and the discomfort of the repeated injections is a disincentive to this form of treatment particularly in pediatric patients. For example, dropout rates exceeding 50% over a multi-year course of injection treatment have been reported. Alternative routes for immunotherapy have been explored, especially in Europe in an attempt to improve patient compliance and to minimize the risk of serious adverse reactions. For example, sublingual-oral immunotherapy (SLIT), which is the administration of the allergenic extract/vaccine under the tongue for 1-2 minutes followed by swallowing, has been proven to be efficacious and safe in several double-blind, placebo-controlled studies. A recent Cochrane Review concluded, "SLIT is a safe treatment, which significantly reduces symptoms and medication requirements in allergic rhinitis." Efficacy studies support the use of SLIT for the treatment of rhinitis or rhinitis and asthma. However, dosage schedules are highly variable and optimal maintenance doses have not yet been established. Thus, dosing studies should be designed to investigate not only the safety profile but to determine optimal doses for maintenance therapy of patients built-up by injection IT and for build-up regimens of previously untreated patients. Much of the United States medical community's hesitation to embrace sublingual immunotherapy as a viable treatment option for allergy patients has stemmed from limited information using U.S. licensed allergenic extracts for this treatment route. Additionally, the cost-effectiveness of one form of therapy over the other has not been clearly evaluated and the third-party payers have not accepted SLIT for insurance coverage.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
430
Standardized Ragweed Allergenic Extract, sublingual oral
Placebo, sublingual oral
Scores on a Scale (Average of Daily Rhinoconjunctivitis Symptom Score (RSS) Recorded During the Ragweed Season
Symptom score defined as sum of scores from eight symptoms rated 0-3 (0=absent, 1=mild, 2=moderate, 3=severe): ocular (itchiness, swelling/redness, and watery eyes/tears), nasal (sneezing, itching, runny and stuffy nose), and ears (itching). Average daily RSS ranged from 0-48; A lower score was more favorable. The average daily RSS was computed for each subject by: (1) summing the 8 individual allergy symptoms recorded in the morning (AM RSS) and the evening (PM RSS); (2) forming the daily RSS by summing the AM RSS and the PM RSS for each day of the ragweed season; (3) averaging the daily RSS for the entire ragweed pollen season.
Time frame: Ragweed pollen season, 08/01/08 to 10/30/08, approximately 3 months
Scores on a Scale (Average Daily RSS During the Highest Pollen Count Week)
Symptom score defined as sum of scores from eight symptoms rated 0-3 (0=absent, 1=mild, 2=moderate, 3=severe): ocular (itchiness, swelling/redness, and watery eyes/tears), nasal (sneezing, itching, runny and stuffy nose), and ears (itching). Average daily RSS ranged from 0-48; A lower score was more favorable. The average daily RSS was computed for each subject by: (1) summing the 8 individual allergy symptoms recorded in the morning (AM RSS) and the evening (PM RSS); (2) forming the daily RSS by summing the AM RSS and the PM RSS for each day of the ragweed season; (3) averaging the daily RSS for the entire ragweed pollen season. The highest pollen count week was defined as the 7 contiguous days from the series with the largest average pollen count, and in which the weekly average was computed using at least 4 non-missing daily RSS values (either AM or PM could be present to be considered a valid daily RSS value).
Time frame: 09/01/2008-09/07/2008
Scores on a Scale (Average Daily AM RSS and the Average Daily PM RSS During the Ragweed Season)
Symptom score defined as sum of scores from eight symptoms rated 0-3 (0=absent, 1=mild, 2=moderate, 3=severe): ocular (itchiness, swelling/redness, and watery eyes/tears), nasal (sneezing, itching, runny and stuffy nose), and ears (itching). Average daily RSS ranged from 0-48; A lower score was more favorable. The average daily RSS (the sum of the 8 individual allergy symptoms recorded in the morning (AM RSS) and the evening (PM RSS).
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Sneeze, Wheeze, & Itch Associates
Normal, Illinois, United States
Welborn Clinic
Evansville, Indiana, United States
Iowa Clinical Research Corporation
Iowa City, Iowa, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
College Park Family Care Center
Overland Park, Kansas, United States
Kansas City Allergy and Asthma
Overland Park, Kansas, United States
Family Allergy and Asthma Respiratory Institute
Louisville, Kentucky, United States
Clinical Research Institute
Minneapolis, Minnesota, United States
Clinical Research of the Ozarks
Rolla, Missouri, United States
Midwest Clinical Research, LLC
St Louis, Missouri, United States
...and 20 more locations
Time frame: Ragweed pollen season 08/01/08 to 10/30/08
Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears);
The average daily RSS during the ragweed season for each of the 3 organ systems (ocular, nasal, ears) were separately analyzed to evaluate these individual components of the RSS. Three separate baseline average daily RSS values were computed for this analysis. The modified ITT population was used for this analysis. The range for scores: 0 to 3 for each of eight symptom or a total of 0 to 24 daily RSS. A lower score was more favorable.
Time frame: Ragweed pollen season 08/01/08 to 10/30/08
Scores on a Scale (Total Allergy Relief Medication Score During the Ragweed Season) for Each Subject
Total allergy relief medication score during the ragweed season for each subject. This score is computed for each subject by summing their individual medication scores (excluding beta-agonist use) for the entire ragweed season. High scores were indicative of poor symptom relief from the study medication. The associated relief medication scores assigned to medication are 0-if no medication taken; 3 for each one antihistamine tablet taken; 1 for each 2 antihistamine eye drop administrations, 1 for each 2 antihistamine nasal spray administrations and 1 for each puff of beta-agonist. The maximum medication score was dependent on the cumulative rescue medication use. The lower result the more favorable.
Time frame: Ragweed pollen season 08/01/08 to 10/30/08
Scores on a Scale (The Average Combined Allergy Symptom and Medication Score During the Ragweed Season for Each Subject)
The average combined allergy symptom and medication score during the ragweed season for each subject. This score is computed for each subject by adding their daily relief medication scores (excluding beta-agonist use) and their daily RSS for the entire ragweed season, and then taking the average of the combined scores across days.
Time frame: Ragweed pollen season 08/01/08 to 10/30/08