Asthma, Perennial Allergic Rhinitis
Conditions
Keywords
subcutaneous immunotherapy (SCIT), glycerinated mouse allergenic extract, mouse specific IgE, mouse specific IgG and IgG4, mouse prick skin test wheal
Brief summary
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
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).
Interventions
BIOLOGICALMouse Allergenic Extract
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.
Sponsors
Inner-City Asthma Consortium
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Reported Adverse Events (AEs) | Baseline (Pre-Treatment) through 24 Weeks of Treatment | Frequency of any AEs tabulated by preferred event term. |
| Number of Reported Serious Adverse Events (SAEs) | Baseline (Pre-Treatment) through 24 Weeks of Treatment | Frequency of any Serious Adverse Events (SAEs) throughout the duration of study participation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mouse-Specific IgE Antibodies | Baseline (Pre-Treatment) through Week 24 | 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. |
| Change in Mouse-Specific IgG Antibodies | Baseline (Pre-Treatment) to Week 24 | 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. |
| Change in Mouse-Specific IgG4 Antibodies | Baseline (Pre-Treatment) to Week 24 | 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. |
| Change in In-vitro Mouse Antigen Binding to B-cells | Baseline (Pre-Treatment) to Week 24 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mouse Allergenic Extract Participants received escalating doses of glycerinated mouse allergenic extract administered via the subcutaneous route. The first injection contained 0.05 mL of 1:10,000 concentration of 1:20 weight per volume (w/v) glycerinated mouse allergenic extract. Administration of additional dosages were given at study clinician's discretion, up to a Maximum Study Dose (MSD) of 0.4 mL of extract at a concentration of 1:10 w/v, for the first 11 weeks of the 24-week treatment with two injections per week, separated by at least 2 days. Dose escalation continued until maximum study dose was achieved in a maximum of 18 weeks. For the remaining time of the 24-week treatment, participants received one injection of investigational agent every 2 weeks and were asked to report any symptoms possibly related to the investigation agent to the study sites. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Subject received depot steroid injection | 1 |
Baseline characteristics
| Characteristic | Mouse Allergenic Extract |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 27.3 years STANDARD_DEVIATION 7.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mouse-Specific Serum Immunoglobulin E (IgE) Levels | 2.34 kU/L STANDARD_DEVIATION 0.45 |
| Mouse-Specific Serum Immunoglobulin G4 (IgG4) Levels | 0.08 kU/L STANDARD_DEVIATION 0.35 |
| Mouse-Specific Serum Immunoglobulin G (IgG) Levels | 1.23 kU/L STANDARD_DEVIATION 0.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 6 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Number of Reported Adverse Events (AEs)
Frequency of any AEs tabulated by preferred event term.
Time frame: Baseline (Pre-Treatment) through 24 Weeks of Treatment
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Total adverse events | 9 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Abdominal pain | 1 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Vomiting | 1 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Injection site swelling | 2 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Peak expiratory flow rate decreased | 2 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Pruritus generalized | 1 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Skin lesion | 1 Events |
| Mouse Allergenic Extract | Number of Reported Adverse Events (AEs) | Flushing | 1 Events |
Primary
Number of Reported Serious Adverse Events (SAEs)
Frequency of any Serious Adverse Events (SAEs) throughout the duration of study participation.
Time frame: Baseline (Pre-Treatment) through 24 Weeks of Treatment
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mouse Allergenic Extract | Number of Reported Serious Adverse Events (SAEs) | 0 Number of SAEs |
Secondary
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.
Time frame: Baseline (Pre-Treatment) to Week 24
Population: No analysis conducted: Sponsor's decision to not pursue assay development in this study.
Secondary
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.
Time frame: Baseline (Pre-Treatment) through Week 24
Population: Intent-to-treat
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Mouse Allergenic Extract | Change in Mouse-Specific IgE Antibodies | 3 Ratio |
p-value: <0.00195% CI: [2.09, 4.29]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (Pre-Treatment) to Week 24
Population: Intent-to-treat
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Mouse Allergenic Extract | Change in Mouse-Specific IgG4 Antibodies | 6.55 Ratio |
p-value: <0.00195% CI: [3.87, 11.06]Mixed Models Analysis
Secondary
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.
Time frame: Baseline (Pre-Treatment) to Week 24
Population: Intent-to-treat
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Mouse Allergenic Extract | Change in Mouse-Specific IgG Antibodies | 3.82 Ratio |
p-value: <0.00195% CI: [2.77, 5.25]Mixed Models Analysis