Efficacy Study of Sublingual Immunotherapy to Treat Ragweed Allergies

Condition(s) targeted: Allergic Rhinitis

Intervention: Ragweed Allergenic Extract Immunotherapy (Biological); Ragweed allergenic extract (Biological)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Greer Laboratories

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

Official title: Parallel, Randomized, Double-Blind, Placebo-Controlled Trial in Adults for the Sublingual-Oral Immunotherapy (SLIT) of Allergic Rhinoconjunctivitis With or Without Asthma Caused By Ragweed Pollen

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study

Primary outcome: The primary efficacy variable will be the average daily rhinoconjunctivitis symptom score (RSS) recorded during the ragweed season.

Secondary outcome: Total allergy relief medication score during the ragweed season will be computed for each Subject. This secondary efficacy variable will be computed for each Subject by summing their individual medication scores for the entire ragweed season.

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.

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

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.

Exclusion Criteria:

- Subjects having a history of anaphylaxis or history consistent with persistent asthma

- Subjects taking antihistamines or nasal steroids medications greater than twice a week

in the months of January and/or February.

- Subjects with chronic sinusitis unstable angina, significant arrhythmia, uncontrolled

hypertension, or other chronic or immunological diseases that in the opinion of the investigator might interfere with the evaluation of the test drug or pose additional risk to the Subject.

- Subjects having perennial or structurally related rhinitis or rhinitis medicamentosa

(from excessive use of nasal decongestants) that will interfere with the evaluation of symptoms due to ragweed allergy.

- Subjects with an FEV1 or PEF less than 80% predicted (moderate persistent asthma) with

or without controller medication.

- Subjects who have received an experimental drug in the 30 days prior to admission into

this study or who plan to use an experimental drug during the study.

- Subjects who have received Anti-IgE medications (Xolair) or similar compounds in the

last 12 months.

- Subjects who have received ragweed allergen immunotherapy in the last 3 years prior to

admission into this study.

- Subjects who are current users of inhaled, oral, intramuscular, intravenous

corticosteroids, tricyclic antidepressants, beta blockers, or MAO inhibitors.

- Subjects using beta-agonist more than twice a month unless being taken prior to

exercise.

- Subjects using medications that could induce adverse gastrointestinal reactions during

the study. Subjects using such medications must prove stable with no side effects for at least 3 months prior to enrollment.

- Subjects refusing to sign the EpiPen Training Form will be excluded from the study.

- Pregnant or breast feeding females.

- Subjects who plan to leave the study area for more than 2 consecutive weeks during the

study.

- Subjects with a positive skin prick test to cat and/or dog, and own the pet(s) to

which they are allergic.

- Subjects who sleep during the day due to working third shift.

- Subjects unable to achieve dose #2 or higher during preliminary dosing will be

excluded.

Sneeze, Wheeze, & Itch Associates, Normal, Illinois 61761, United States

Welborn Clinic, Evansville, Indiana 47713, United States

University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United States

Iowa Clinical Research Corporation, Iowa City, Iowa 52240, United States

College Park Family Care Center, Overland Park, Kansas 66210, United States

Kansas City Allergy and Asthma, Overland Park, Kansas 66210, United States

Family Allergy and Asthma Respiratory Institute, Louisville, Kentucky 40215, United States

Clinical Research Institute, Minneapolis, Minnesota 55402, United States

Midwest Clinical Research, LLC, St. Louis, Missouri 63141, United States

Clinical Research of the Ozarks, Rolla, Missouri 64501, United States

Midwest Allergy and Asthma Clinic, PA, Omaha, Nebraska 68130, United States

Creighton University, Omaha, Nebraska 68131, United States

Asthma, Immunology and Allergy Association, LLC, Lincoln, Nebraska 68505, United States

Ocean Allergy and Respiratory Research Center, Brick, New Jersey 08724, United States

Pulmonary and Allergy Associates, PA, Summit, New Jersey 07901, United States

Bernstein Clinical Research Center, Cincinnati, Ohio 45231, United States

Allergy and Respiratory Center, Canton, Ohio 44718, United States

Cleveland Clinic, Cleveland, Ohio 44195, United States

Toledo Center for Clinical Research, Sylvania, Ohio 43560, United States

Oklahoma Allergy & Asthma Clinic, PC, Oklahoma City, Oklahoma 73104, United States

Allergy, Asthma and Clinical Research Center, Oklahoma City, Oklahoma 73120, United States

Allergy and Asthma Specialists, PC, Blue Bell, Pennsylvania 19422, United States

Asthma and Allergy Research Associates, Upland, Pennsylvania 19013, United States

Valley Clinical Research Center, Bethlehem, Pennsylvania 18020, United States

Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, United States

Vanderbilt ASAP Research, Nashville, Tennessee 08724, United States

Pharmaceutical Research & Consulting, Inc, Dallas, Texas 75231, United States

Aurora Advanced Healthcare, Inc, Milwaukee, Wisconsin 53209, United States

University of Wisconsin, Madison, Wisconsin 53792, United States

Allergy, Asthma and Sinus Center, SC, Greenfield, Wisconsin 53228, United States

Starting date: March 2008
Ending date: October 2008
Last updated: June 11, 2008