Allergic Rhinitis
Conditions
Keywords
Allergy, Sublingual Immunotherapy, Allergic Rhinitis
Brief summary
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
Detailed description
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.
Interventions
BIOLOGICALStandardized Ragweed Allergenic Extract
Standardized Ragweed Allergenic Extract, sublingual oral
BIOLOGICALPlacebo
Placebo, sublingual oral
Sponsors
Greer Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Adult ragweed-sensitive Subjects with allergic rhinoconjunctivitis with or without asthma during ragweed pollen season. * Subjects must be 18 to 50 years of age. * Test Subjects will have a history of moderate to severe isolated or unseasonal allergic rhinoconjunctivitis with or without mild intermittent asthma symptoms attributable to ragweed pollen for a minimum of 2 years before study entry. * Subjects with or with out a history of asthma will possess FEV1 and PEF greater than or equal to 80% predicted at the beginning of the study established by spirometry and defined by the Knudson predicted set. * Sensitivity to the relevant allergen will be documented by a positive skin prick test result performed along with negative (saline) and positive (histamine) control skin tests. A positive test will be defined as the skin reaction having the longest wheal diameter of 5mm or greater or the longest erythema diameter of 10 mm or greater at 15-20 minutes after application. * All female Subjects of child-bearing potential will be required to provide a urine sample for pregnancy testing that must be negative before being allowed to participate in the study. * Subjects must be planning to remain in the study area during the trial (see
Exclusion criteria
# 14). * Subjects must be trained on the proper use of the EpiPen, and sign the EpiPenTraining Form before being allowed to enroll in the study. * Subjects must be mentally and physically capable of self-administering oral drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scores on a Scale (Average of Daily Rhinoconjunctivitis Symptom Score (RSS) Recorded During the Ragweed Season | Ragweed pollen season, 08/01/08 to 10/30/08, approximately 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Scores on a Scale (Average Daily RSS During the Highest Pollen Count Week) | 09/01/2008-09/07/2008 | 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). |
| Scores on a Scale (Average Daily AM RSS and the Average Daily PM RSS During the Ragweed Season) | Ragweed pollen season 08/01/08 to 10/30/08 | 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). |
| Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Ragweed pollen season 08/01/08 to 10/30/08 | 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. |
| Scores on a Scale (Total Allergy Relief Medication Score During the Ragweed Season) for Each Subject | Ragweed pollen season 08/01/08 to 10/30/08 | 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. |
| Scores on a Scale (The Average Combined Allergy Symptom and Medication Score During the Ragweed Season for Each Subject) | Ragweed pollen season 08/01/08 to 10/30/08 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Ragweed allergenic extract administer once daily at 77.3 Units/Amb a 1. | 216 |
| Placebo Placebo to be administered once daily at 0.0 Units/Amb a 1 | 214 |
| Total | 430 |
Baseline characteristics
| Characteristic | Active | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 216 Participants | 214 Participants | 430 Participants |
| Age, Continuous | 35.8 years STANDARD_DEVIATION 9.54 | 35.5 years STANDARD_DEVIATION 9.24 | 35.6 years STANDARD_DEVIATION 9.38 |
| Region of Enrollment United States | 216 participants | 214 participants | 430 participants |
| Sex: Female, Male Female | 138 Participants | 127 Participants | 265 Participants |
| Sex: Female, Male Male | 78 Participants | 87 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 216 | 0 / 214 |
| serious Total, serious adverse events | 3 / 216 | 0 / 214 |
Outcome results
Primary
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
Population: The modified ITT population: subjects with 12 weeks or more of treatment (based on subject consent date and date of ragweed season for the site)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Scores on a Scale (Average of Daily Rhinoconjunctivitis Symptom Score (RSS) Recorded During the Ragweed Season | 6.2 Scores on a scale | Standard Deviation 6.2 |
| Placebo | Scores on a Scale (Average of Daily Rhinoconjunctivitis Symptom Score (RSS) Recorded During the Ragweed Season | 6.5 Scores on a scale | Standard Deviation 5.61 |
p-value: <0.0595% CI: [-1.15, 0.48]ANCOVA
Secondary
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).
Time frame: Ragweed pollen season 08/01/08 to 10/30/08
Population: The modified ITT population: subjects with 12 weeks or more of treatment (based on subject consent date and date of ragweed season for the site)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Scores on a Scale (Average Daily AM RSS and the Average Daily PM RSS During the Ragweed Season) | Average Daily AM RSS | 3.5 Scores on a scale | Standard Deviation 3.64 |
| Active | Scores on a Scale (Average Daily AM RSS and the Average Daily PM RSS During the Ragweed Season) | Average Daily PM RSS | 3.5 Scores on a scale | Standard Deviation 3.47 |
| Placebo | Scores on a Scale (Average Daily AM RSS and the Average Daily PM RSS During the Ragweed Season) | Average Daily AM RSS | 3.8 Scores on a scale | Standard Deviation 3.22 |
| Placebo | Scores on a Scale (Average Daily AM RSS and the Average Daily PM RSS During the Ragweed Season) | Average Daily PM RSS | 3.6 Scores on a scale | Standard Deviation 3.11 |
Secondary
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
Population: The modified ITT population: subjects with 12 weeks or more of treatment (based on subject consent date and date of ragweed season for the site)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Scores on a Scale (Average Daily RSS During the Highest Pollen Count Week) | 7.0 scores on a scale | Standard Deviation 6.96 |
| Placebo | Scores on a Scale (Average Daily RSS During the Highest Pollen Count Week) | 7.5 scores on a scale | Standard Deviation 7.03 |
p-value: <0.0595% CI: [-1.72, 0.63]ANCOVA
Secondary
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
Population: The modified ITT population: subjects with 12 weeks or more of treatment (based on subject consent date and date of ragweed season for the site)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Ocular | 1.7 Scores on a scale | Standard Deviation 2.44 |
| Active | Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Ears | 0.5 Scores on a scale | Standard Deviation 0.94 |
| Active | Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Nasal | 4.0 Scores on a scale | Standard Deviation 3.55 |
| Placebo | Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Ocular | 1.9 Scores on a scale | Standard Deviation 2.12 |
| Placebo | Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Ears | 0.5 Scores on a scale | Standard Deviation 0.7 |
| Placebo | Scores on a Scale (Average Daily RSS During the Ragweed Season for Each of the Three Organ) Systems (Ocular, Nasal, Ears); | Nasal | 4.2 Scores on a scale | Standard Deviation 3.41 |
Secondary
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
Population: The modified ITT population: subjects with 12 weeks or more of treatment (based on subject consent date and date of ragweed season for the site)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Scores on a Scale (The Average Combined Allergy Symptom and Medication Score During the Ragweed Season for Each Subject) | 6.7 Scores on a scale | Standard Deviation 6.85 |
| Placebo | Scores on a Scale (The Average Combined Allergy Symptom and Medication Score During the Ragweed Season for Each Subject) | 7.3 Scores on a scale | Standard Deviation 6.69 |
Secondary
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
Population: The modified ITT population: subjects with 12 weeks or more of treatment (based on subject consent date and date of ragweed season for the site)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active | Scores on a Scale (Total Allergy Relief Medication Score During the Ragweed Season) for Each Subject | 40.5 Scores on a scale | Standard Deviation 85.59 |
| Placebo | Scores on a Scale (Total Allergy Relief Medication Score During the Ragweed Season) for Each Subject | 50.1 Scores on a scale | Standard Deviation 137 |