Texan Allergy & Sinus Center Mountain Cedar Intra-Lymphatic Immunotherapy Study

Study Overview
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Brief Summary
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TX-SMILE is an investigator-initiated, multi-center, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety, and tolerability of intra-lymphatic administration of an approved allergenic extract for the immunotherapy treatment of allergic rhinitis and conjunctivitis due to pollen from the conifer Mountain Cedar.

Detailed Description
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TX-SMILE is an investigator-initiated, multi-center, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety, and tolerability of an alternative injection site and associated adjustments to dosing and treatment regimen for allergen immunotherapy with a commercially-available, FDA-approved allergenic extract for the immunotherapy treatment of allergic rhinitis and conjunctivitis due to pollen from the conifer Mountain Cedar (Juniperus ashei). The purpose of this study is to evaluate the effect of a three-dose treatment series of ultrasonography-guided, intra-lymphatic immunotherapy injections over a two-month period prior to the start of the 2018-2019 Mountain Cedar allergy season in central Texas. Patients will be evaluated for safety and tolerability during the treatment period and for efficacy during the 2018-2019 Texas Mountain Cedar pollen season.

Official Title
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Texan Allergy & Sinus Center Mountain Cedar Intra-Lymphatic Immunotherapy Study

Conditions
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Allergic Rhinitis Due to Tree Pollen, Allergic Conjunctivitis, Allergic Rhinoconjunctivitis

Intervention / Treatment
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* Biological: Intra-lymphatic allergenic extract
* Biological: Intra-lymphatic placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both male and female adult patients with a history of Season Allergic Rhinitis (SAR) with bothersome symptoms due to Mountain Cedar pollinosis confirmed using the Modified Quantitate Test (MQT; defined as a wheal greater than or equal to 3 millimeters larger than the diluent control) Patients must be willing to provide written, informed consent Patients must be willing and able to comply with study procedures Women of childbearing potential must agree to use an acceptable form of contraception during the trial Exclusion Criteria: Patients less than 18 years of age Clinically-significant chronic sinusitis, as determined by the investigator History of anaphylaxis during Mountain Cedar skin prick testing Participation in another clinical trial or use of an experimental medication within 30 days of enrollment Medically significant co-morbidities that, in the opinion of the investigator, place the subject at increased risk during the study, including but not limited to: Autoimmune diseases, other than allergic rhinitis (AR), stable allergic asthma, eczema and food sensitivities Pulmonary or respiratory diseases other than stable asthma Cancer other than basal cell carcinoma Coronary artery disease or hypertension treated with beta-blockers Clinically significant impairment of renal or hepatic function Use of concomitant medications that, in the opinion of the investigator, may reduce the effectiveness of rescue treatments for anaphylaxis (e.g. beta-blockers) or alter the immune response to allergen immunotherapy (e.g., immunosuppressants, systemic corticosteroids) Previously completed immunotherapy for Mountain Cedar pollinosis, that in the opinion of the investigator would interfere with the assessment or treatment of the patient Inability to access suitable lymph nodes for intralympahtic injections Plans to leave the area for a significant period of the upcoming Mountain Cedar pollen season Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-lymphatic allergenic extract<br>A series of three injections of 0.1 mL (about 2 drops) of the allergenic extract of Mountain Cedar Pollen given every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. | Biological: Intra-lymphatic allergenic extract<br>* Mountain Cedar pollen allergenic extract is an FDA-approved, commercially available product for diagnosis and hypo-sensitization treatment of allergies. The labeled use is deep subcutaneous or percutaneous injection. Hyposensitization treatment is typically a series of 30 - 70 injections over 3 - 5 years into the upper aspect of the arm. This investigation is a proof-of-concept study to evaluate an alternative hyposensitization regimen of 3 injections directly into an inguinal lymph node.<br>* Other names: NDC02686614;|
| Placebo Comparator: Intra-lymphatic placebo<br>Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. | Biological: Intra-lymphatic placebo<br>* The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Daily Total Combined Score (TCS) | The TCS is the preferred endpoint for rhinoconjunctivitis as recommended by the European Academy of Allergy and Clinical Immunology. Scoring of the TCS is from 0 to 38 on each day that it is assessed. The TCS is the sum of the symptom scores for runny nose, stuff nose, sneezing, itchy nose, gritty/itchy eyes, and watery eyes rated from no symptoms = 0 to severe symptoms = 3 plus the score for use of rescue medications for allergy symptoms 6 points for oral antihistamine, 6 points for eye drops, and 8 points for a nasal corticosteroid. Thus, a lower score represents fewer symptoms and associated need for allergy medication, while a higher score reflects more severe symptoms and the use of medication to treat symptoms. The TCS will be measured during the 2018-2019 Mountain Cedar pollen se | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Peak Pollen Season Days With a Lower Group Average Total Combined Score | Evaluated during the 2018-2019 Texas Mountain Cedar allergy season. The number of days with a lower group average Total Combined Score, comparatively, in each Arm/Group are reported. Scoring of the TCS is from 0 to 38 on each day that it is assessed.The TCS is the sum of the symptom scores for runny nose, stuff nose, sneezing, itchy nose, gritty/itchy eyes, and watery eyes rated from no symptoms = 0 to severe symptoms = 3 plus the score for use of rescue medications for allergy symptoms 6 points for oral antihistamine, 6 points for eye drops, and 8 points for a nasal corticosteroid. Thus, a lower score represents fewer symptoms and associated need for allergy medication, while a higher score reflects more severe symptoms and the use of medication to treat symptoms. | Assessed up to 4 months, number of actual peak pollen season days was 27 | 
| Patient Reported Pain or Discomfort Following Intra-lymphatic Injections | Patient reported pain will be measured immediately after ILIT procedure using the Numeric Rating Scale 11 (NRS-11 rating scale). The NRS-11 asks patients to rate their pain on a scale from 0 (no pain or discomfort) to 11 (worst possible pain). | Immediately after the ILIT procedure | 
| Patient-reported Treatment Satisfaction at the End of Study | Percentage of patients reporting satisfaction with their treatment | Up to 4 months | 
| Percentage Change in Allergen-specific Serum IgE | Percentage change in allergen-specific serum IgE from baseline to the end-of-study visit between active ILIT and placebo. | Assessed prior to the first injection and to 4-8 weeks after the end of the 2018-2019 pollen season | 
| Total Safety Score (TSS) for Active and Placebo Treatment Groups | The total safety score is a is based on World Allergy Organization grading for allergic reactions. Following allergen or placebo exposure via intra-lymphatic injection, patients are monitored for local and systemic allergic reactions for up to 60 minutes post-procedure. At each exposure, a score is rated on a scale from none = 0, local reactions only = 1, mild systemic reactions (WAO Grade 1/2) = 2, moderate systemic reaction (WAO Grade 3) = 3, and severe systemic reaction (WAO grade 4) = 4. The total safety score for each group is the sum of the individual scores of each patient across all three treatments (exposures). Thus, the subject may have a score from 0 to 12 with 0 reflecting no allergic reaction to the allergen and 12 reflecting severe allergic reactions, and the TSS for a group is the sum for all patients in the group. The TSS is used to elicit and grade adverse events of interest rather than for statistical analysis. | 8 weeks | 
| Number of Subjects Who: Experienced Anaphylaxis, Were Treated With Epinephrine, or Experienced Any Other Treatment-emergent SAE Within 60 Minutes of Any of Three Planned ILIT Procedures | To evaluate the safety of ILIT for Mountain Cedar pollinosis relative to placebo control based on the proportion of subjects receiving allergenic extract versus the proportion of subjects receiving placebo that: experience anaphylaxis, or are treated with epinephrine, or experience any other treatment-emergent, serious adverse event (SAE) within 60 minutes of any of the three planned ILIT procedures. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mountain Cedar, Juniperus Ashei, Pollinosis, Intra-lymphatic