Subcutaneous Immunotherapy for Mouse in Adults

Study Overview
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Brief Summary
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This is an open label trial of mouse allergenic extract administered by subcutaneous injection in adults with asthma and mouse sensitivity. The study is designed to evaluate: the safety of this therapy when given by injection biomarkers of the immune response and whether the therapy would be effective in treating allergic asthma.

Detailed Description
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The primary objective of the study is to assess if treatment with mouse subcutaneous immunotherapy (SCIT), using the per protocol allergenic extract doses, is safe. This will be done by determining the rate of related adverse events and serious adverse events in the course of treatment. Secondary objectives include: determination of whether a 24 week treatment with mouse SCIT, using the per protocol allergenic extract doses, will induce a 3-fold increase in mouse-specific serum immunoglobulin E (IgE) determination of whether a 24 week treatment with mouse SCIT, using the per protocol allergenic extract doses, will induce changes in the serum levels of mouse-specific immunoglobulin G (IgG) and immunoglobulin subclass 4 (IgG4).

Official Title
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A Biomarker-Based Pilot Study of Mouse Subcutaneous Immunotherapy in Mouse Sensitive Adults With Asthma and/or Perennial Allergic Rhinitis (ICAC-26)

Conditions
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Asthma, Perennial Allergic Rhinitis

Intervention / Treatment
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* Biological: Mouse Allergenic Extract


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Participants who meet any of the following criteria are not eligible for enrollment but may be reassessed. Participants are ineligible if they: Are pregnant or lactating. Females must be abstinent or use a medically acceptable birth control method throughout the study (e.g. oral, subcutaneous, mechanical, or surgical contraception); Cannot perform spirometry at Screening; Have an asthma severity classification at Recruitment of severe persistent, using the NAEPP classification, as evidenced by at least one of the following: Requires a dose of greater than 500 mcg of fluticasone per day or the equivalent of another inhaled corticosteroid; Have received more than 2 courses of oral or parenteral corticosteroids within the last 12 months; Have been treated with depot steroids within the last 12 months; Have been hospitalized for asthma within the 6 months prior to recruitment; Have had a life-threatening asthma exacerbation that required intubation, mechanical ventilation, or that resulted in a hypoxic seizure within 2 years prior to recruitment. Do not have access to a phone (needed for scheduling appointments); Have received allergen immunotherapy (SLIT or SCIT) in the last 12 months prior to recruitment or who plan to initiate or resume allergen immunotherapy during the study; Have previously been treated with anti-IgE therapy within 1 year of recruitment; Have received an investigational drug in the 30 days prior to recruitment or who plan to use an investigational drug during the study; Refuses to sign the Epinephrine Auto-injector Training Form. EXCLUSION CRITERIA Participants who meet any of the following criteria are not eligible for enrollment and may not be reassessed. Participants are ineligible if they: Do not primarily speak English; Plan to move from the area during the study period; Have a history of idiopathic anaphylaxis or anaphylaxis grade 2 or higher as defined per protocol; Have unstable angina, significant arrhythmia, uncontrolled hypertension, history of autoimmune disease, or other chronic or immunological diseases that in the opinion of the investigator might interfere with the evaluation of the investigational agent or pose additional risk to the participant; Are using tricyclic antidepressants or beta-adrenergic blocker drugs (both oral and topical); Have not received the seasonal Flu (Influenza) Vaccine if enrolling December through March.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mouse Allergenic Extract<br>Participants will receive escalating doses of glycerinated mouse allergenic extract administered via the subcutaneous route up to a Maximum Study Dose (MSD) of 0.4 mL of extract at a concentration of 1:10 wt/vol. | Biological: Mouse Allergenic Extract<br>* Subjects will receive escalating doses of glycerinated mouse allergenic extract administered subcutaneously up to a maximum study dose (MSD) of 0.4 mL of extract at a concentration of 1:10 wt/vol., per protocol.<br>* Other names: allergenic extract of Mus musculus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Reported Adverse Events (AEs) | Frequency of any AEs tabulated by preferred event term. | Baseline (Pre-Treatment) through 24 Weeks of Treatment | 
| Number of Reported Serious Adverse Events (SAEs) | Frequency of any Serious Adverse Events (SAEs) throughout the duration of study participation. | Baseline (Pre-Treatment) through 24 Weeks of Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mouse-Specific IgE Antibodies | Serum Immunoglobulin E (IgE) is an antibody produced by the immune system. If a participant has an allergy, the immune system will respond to that particular allergen by producing IgE antibodies. These antibodies travel to cells that release chemicals, causing allergic reactions. This endpoint/outcome is the ratio of geometric means for baseline mouse-specific serum IgE versus post-baseline mouse-specific serum IgE. The numerator is the geometric mean post-baseline IgE and the denominator is baseline IgE. A ratio of greater than 1 would indicate an increase in IgE throughout the course of the study. | Baseline (Pre-Treatment) through Week 24 | 
| Change in Mouse-Specific IgG Antibodies | Serum Immunoglobulin G (IgG) is an antibody produced by the immune system. If a participant has bacterial or viral infections, the immune system will respond to that particular infection by producing IgG antibodies. This endpoint/outcome is the ratio of geometric means for baseline mouse-specific serum IgG versus post-baseline mouse-specific serum IgG. The numerator is the geometric mean post-baseline IgG and, the denominator is the baseline IgG. A ratio of greater than 1 would indicate an increase in IgG throughout the course of the study. | Baseline (Pre-Treatment) to Week 24 | 
| Change in Mouse-Specific IgG4 Antibodies | Serum Immunoglobulin G4 (IgG4) is a subtype of antibody produced by the immune system. If a participant has bacterial or viral infections, the immune system will respond to that particular infection by producing IgG4 antibodies. This endpoint/outcome is the ratio of geometric means for baseline mouse-specific serum IgG4 versus post-baseline mouse-specific serum IgG4. The numerator is the geometric mean post-baseline IgG4 and, the denominator is the baseline IgG4. A ratio of greater than 1 would indicate an increase in IgG4 antibodies throughout the course of the study. | Baseline (Pre-Treatment) to Week 24 | 
| Change in In-vitro Mouse Antigen Binding to B-cells | The plan was to analyze serum from cockroach subcutaneous immunotherapy (SCIT)-treated participants to determine if treatment inhibits in-vitro mouse antigen binding to B-cells after 6-months of treatment with mouse SCIT, using the per protocol allergenic extract doses. However, the Sponsor cancelled pursuit of mouse immunotherapy within its program at this time due to assay development complexities and cost; thus, there are no analyses/results for this endpoint/outcome. | Baseline (Pre-Treatment) to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subcutaneous immunotherapy (SCIT), glycerinated mouse allergenic extract, mouse specific IgE, mouse specific IgG and IgG4, mouse prick skin test wheal