Allergy, Asthma
Conditions
Keywords
Perennial Allergic Rhinitis, Asthma, Sublingual Immunotherapy (SLIT)
Brief summary
Immunotherapy may help reduce symptoms of allergy and asthma. Problems concerning compliance and adverse events with subcutaneous allergen immunotherapy have generated interest in delivering immunotherapy sublingually (under the tongue). The purpose of this study is to evaluate the safety of a cockroach extract given sublingually to people with perennial (year-round) allergic rhinitis, with or without asthma.
Detailed description
The prevalence of asthma has dramatically increased in many parts of the world. Currently, there is no effective way to prevent development of allergic rhinitis and asthma and no cure. Sublingual immunotherapy (SLIT), a type of therapy in which allergens are placed under the tongue, may be a way to control and possibly prevent allergic rhinitis and asthma. However, detailed research of this approach is limited. The purpose of this study is to evaluate the safety and tolerability of a sublingual cockroach extract given to people with perennial allergic rhinitis. Participants in this study will include people both with and without asthma. Participation in this study will last a little more than 2 weeks. Participants will be stratified by age (oldest to youngest age group) and degree of cockroach sensitivity. Each age group will be enrolled after the previous group's safety data have been reviewed. At study entry (Day 0), participants will receive a dose of placebo and then up to seven incremental doses of cockroach extract at 15-minute intervals while observed by the clinic nurse. Doses will continue to be given until a sign or symptom occurs that indicates the participant is having difficulty tolerating the drug, or until the maximum study dose is reached. At the Principal Investigator's discretion, participants who were able to achieve the maximum study dose will be invited to continue onto the 2-week treatment course of the study. These participants will return on Days 1 and 2 to the clinic to self-administer the maximum study dose of cockroach extract. After self-administering the maximum study dose, participants will be observed by the clinic nurse for 30 minutes. On Days 3 through 14, participants will take the maximum study dose of cockroach extract daily at home. Participants will be asked to keep a diary and record signs or symptoms experienced after taking each dose. Skin tests, breathing tests, and blood collection will occur at study screening. At study entry, participants will be taught to use an EpiPen in the event of a severe allergic reaction at any time during the study. A physical exam/fitness assessment will be done at study screening, study entry, and the final visit. Unused extract will be collected at the final visit from participants who entered the 2-week treatment course of the study. The reference for this study is SCSS (Sublingual Cockroach Safety Study) in the provided citation: Wood RA, Togias A, Wildfire J et al. Development of cockroach immunotherapy by the Inner-City Asthma Consortium. J Allergy Clin Immunol. 2014 Mar;133(3):846-52. PubMed ID: 24184147).
Interventions
Initially each subject underwent a 1-day, 8-dose escalation (e.g., one dose of placebo, 0.14 milliliters \[mL\], followed by 7 escalating doses of Glycerinated German Cockroach Allergenic Extract until the Maximum Study Dose \[0.42 mL, 1:10 wt/vol\] or Maximum Tolerated Dose was achieved). This maximum dose became the daily dose - maintenance dose- of Glycerinated German Cockroach Allergenic Extract for the following 14 days.The maintenance dose of 0.42 mL was calculated to contain 3685 bioequivalent allergy units (BAU), with approximately 4.2 mg of German cockroach allergen Bla g 2 and 50 mg of Bla g 1 per dose. Route of administration: sublingual-oral route.
DRUGPlacebo
Placebo was administered only as the first dose (e.g., representing no Glycerinated German Cockroach bioequivalent allergy units) during the initial 1-day, 8-dose escalation, otherwise referred to as the Preliminary Dosing Visit. Refer to the Glycerinated German cockroach allergenic extract treatment for more details. Route of administration: sublingual-oral route.
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
5 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
for All Participants: * History of perennial allergic rhinitis with or without asthma for a minimum of 1 year prior to study entry * Positive skin prick test to German cockroach performed along with negative (saline) and positive (histamine) controls * Willing to sign EpiPen training form * Parent or guardian willing to provide informed consent, if applicable Inclusion Criteria for Participants with Asthma: * Diagnosis of well-controlled, mild to moderate persistent asthma, defined as having symptoms at least 3 times a week with no controller medication OR less than 3 times a week on controller medication. More information about this criterion can be found in the protocol. * Diagnosis of asthma made over 1 year prior to study entry
Exclusion criteria
* Have severe, persistent asthma (according to National Asthma Education and Prevention Program \[NAEPP\] classification) as evidenced by those who require a dose of greater than 500 mcg of fluticasone/day or equivalent of another inhaled corticosteroid OR who have been hospitalized for asthma within 6 months prior to study entry * Life-threatening asthma exacerbation requiring intubation or mechanical ventilation or resulting in a hypoxic seizure in the 2 years prior to study entry * History of anaphylaxis of Grade 2 or higher as defined in the protocol * Unstable angina, significant arrhythmia, uncontrolled hypertension, or other chronic or immunologic diseases that, in the opinion of the investigator, may interfere with the study or pose additional risk to the patient. More information about this criterion can be found in the protocol. * Taking medications that could induce gastrointestinal reactions during the study. Participants taking such medications must prove to be stable with no side effects for at least 3 months prior to study screening to be considered eligible. * Received an investigational drug in the 30 days prior to study entry OR plan to receive an investigational drug during the study * Received allergen immunotherapy in the 180 days prior to screening or plan to initiate or resume allergen immunotherapy during the study * Taking tricyclic antidepressants or beta-adrenergic blocker drugs * Received omalizumab in the 3 months prior to study screening * Known contraindication to therapy with cockroach extract used in this study * Mental illness that would interfere with the participant's ability to comply to study requirements * History of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the study * Plan to leave study area during the study * Does not primarily speak English, including caretakers of participants when the participant is a child * Cannot perform spirometry * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Discontinue Study | Initial placebo dose to end of 2-week treatment course (maximum study dose) | Proportion of participants who discontinued study for any reason following initiation of treatment (any participant who receives the initial placebo dose will be considered initiated onto treatment) |
Countries
United States
Participant flow
Recruitment details
The result tables represent the safety population: all subjects that initiated the 1-day, 8-dose escalation, otherwise referred to as the Preliminary Dosing Visit. One subject in the 8-17 age group withdrew from the study after this timepoint and was replaced with another participant.
Participants by arm
| Arm | Count |
|---|---|
| German Cockroach Allergen Dosing Group Initially each subject underwent a 1-day, 8-dose escalation (e.g., one dose of placebo, 0.14 milliliters \[mL\], followed by 7 escalating doses of Glycerinated German Cockroach Allergenic Extract until the Maximum Study Dose \[0.42 mL, 1:10 wt/vol\] or Maximum Tolerated Dose was achieved). This maximum dose became the daily dose - maintenance dose- of Glycerinated German Cockroach Allergenic Extract for the following 14 days.The maintenance dose of 0.42 mL was calculated to contain 3685 bioequivalent allergy units (BAU), with approximately 4.2 mg of German cockroach allergen Bla g 2 and 50 mg of Bla g 1 per dose. Route of administration: sublingual-oral route. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non-compliance with study treatment | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | German Cockroach Allergen Dosing Group |
|---|---|
| Age, Categorical <=18 years | 19 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Customized 18-55 years | 9 participants |
| Age, Customized 5-7 years | 9 participants |
| Age, Customized 8-17 years | 10 participants |
| Asthma status (Mild-to-moderate persistent asthma) No | 18 participants |
| Asthma status (Mild-to-moderate persistent asthma) Yes | 10 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| German Cockroach Skin Test Sensitivity High | 18 participants |
| German Cockroach Skin Test Sensitivity Low | 10 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Proportion of Participants Who Discontinue Study
Proportion of participants who discontinued study for any reason following initiation of treatment (any participant who receives the initial placebo dose will be considered initiated onto treatment)
Time frame: Initial placebo dose to end of 2-week treatment course (maximum study dose)
Population: Safety Population: All study participants who were initiated onto the initial placebo study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| German Cockroach Allergen Dosing Group | Proportion of Participants Who Discontinue Study | 7.1 Percentage of Participants |