Sublingual Immunotherapy Studies for Grass and Dust Mite Allergies

Study Overview
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Brief Summary
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This is a study for children and adults who are interested in a new therapy for their allergies to dust mite and timothy grass. The new therapy is called sublingual immunotherapy and the investigators are testing if it is safe and well tolerated.

Detailed Description
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This is a phase I, single-center, randomized, placebo-controlled study of sublingual immunotherapy (SLIT) in pediatric and adult subjects with both house dust mite (HDM) and timothy grass (TG) allergies. We will evaluate whether Dermatophagoides farinae (DF) and/or TG allergen SLIT is safe in children and adults. We will also determine whether treatment with DF and/or TG SLIT reduces the severity of allergic symptoms (allergic rhinitis, allergic conjunctivitis) and enhances their resolution. The study will also evaluate whether SLIT provides a robust durability of response once it is terminated. The dosing-phase of the study will last up to 12 months. In addition, a follow up period of 2 years will occur. Approximately 10 subjects will be on placebo, and 20 on active treatment.

Official Title
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Phase 1 Single Center, Randomized, Controlled Study Using Sublingual Immunotherapy for Timothy Grass and Dust Mite Allergies

Conditions
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Asthma, Allergies, Allergic Rhinitis

Intervention / Treatment
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* Drug: sublingual immunotherapy
* Drug: placebo sublingual immunotherapy


Participation Criteria
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Eligibility Criteria
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SUBJECT INCLUSION CRITERIA: Pediatric and adult timothy grass- and Dermatophagoides farinae-sensitive subjects with allergic rhinoconjunctivitis with or without asthma perennially or during grass pollen season. Subjects must be 5 years of age or older. Sensitivity to the relevant allergen will be documented by a positive skin prick test result (see Appendix E for details). All female subjects of child-bearing potential will be required to provide a urine sample for pregnancy testing that must be negative one week before being allowed to participate in the study. Subjects must be planning to remain in the study area during the trial. Subjects and/or their parents must be trained on the proper use of the Epi-Pen to be allowed to enroll in the study. Subjects and/or their parents must be mentally and physically capable of self-administering oral drug. SUBJECT EXCLUSION CRITERIA: No absolute contraindications to allergen skin testing and/or sublingual immunotherapy are known. However, the risk of serious systemic anaphylactic reactions to pollen or any potent allergenic extract suggests a number of preexisting conditions that should be considered relative contraindications. Among those conditions are acute infections, autoimmune disease, severe cardiac disease, and treatment with beta-adrenergic antagonistic drugs (beta-blockers). Subjects having a history of unexplained anaphylaxis within 2 years or a history of multiple (≥2) episodes of anaphylaxis in the past year, frequent allergic or non-allergic urticaria, or history consistent with poorly controlled persistent asthma. Anaphylaxis must be medically diagnosed. Subjects with unstable angina, significant arrhythmia, uncontrolled hypertension, chronic sinusitis, or other chronic or immunological diseases that in the mind of the investigator might interfere with the evaluation or administration of the test drug or pose additional risk to the subject e.g. gastrointestinal or gastroesophageal disease, chronic infections, scleroderma, hepatic and gallbladder disease, chronic non-allergic pulmonary disease. Subject 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 last 30 days prior to admission into this study or who plan to use an experimental drug during the study. Subjects who have received timothy grass or dust mite allergen immunotherapy within 3 years prior to admission in this study. Subjects who are current users of oral, intramuscular, or intravenous corticosteroids, tricyclic antidepressants, or are taking a beta-blocker (oral or topical). Subjects routinely using medication that could induce adverse gastrointestinal reactions during the study. Subjects refusing to sign the EpiPen Training Form (see Appendix F). Pregnant or breast feeding females. Subjects who have any symptoms at dose levels 1 or 2 at the Preliminary Dosing Visit (see, below). Subjects with significant pet allergies who have significant exposure at home or at work.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sublingual immunotherapy<br>Subjects will take sublingual immunotherapy who have dust mite and timothy grass allergies | Drug: sublingual immunotherapy<br>* Sublingual immunotherapy is provided in an extract form under IND 13485 and dosed safely through a maintenance dose of 12 months.<br>|
| Placebo Comparator: placebo arm<br>The placebo arm will be double blinded and is an important control in SLIT therapies | Drug: sublingual immunotherapy<br>* Sublingual immunotherapy is provided in an extract form under IND 13485 and dosed safely through a maintenance dose of 12 months.<br>Drug: placebo sublingual immunotherapy<br>* SLIT placebo will be the same color and consistency of the active drug arm to provide double blinding<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome is safety | We will assess safety outcomes according to GCP/CFR and NIAID guidelines | 2008-2014 (6 years) | 
| The number of adverse events in the placebo vs the treatment arm will be compared | Adverse events will be defined by GCP/CFR and by NIAID guidelines. | 2008-2016 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergy, immunology, immune tolerance, immunotherapy