Allergy
Conditions
Keywords
Sublingual Immunotherapy (SLIT), Non-seasonal allergic rhinitis, Immunotherapy, Allergic rhinitis, Cat, Perennial allergy, Non-seasonal allergy
Brief summary
The purpose of this study is to identify an effective dose of allergen-specific immunotherapy for cat hair (Felis domesticus) administered by the oral/sublingual route.
Detailed description
This was a phase 2, randomized, double-blind, placebo-controlled, parallel groups study conducted in 3 centers in the US (NCT00689299). Study drug was sublingually dosed once daily as 0.15 mL of US standardized cat hair extract dosed either undiluted, as 1:10 dilution, or placebo. Target dose was obtained on Day 3 of dose titration escalating through 1:100 and 1:10 dilutions on Day 1 and Day 2 in the high dose group or placebo and 1:100 dilutions in the low dose group. Treatment duration was 20 weeks. Adult (\>18 years) study subjects had positive history for cat allergy without asthma, positive skin test to cat allergen, absence of immunotherapy during the prior 2 years, and absence of other confounding baseline conditions. The primary outcome parameter was average Total Symptom Score (TSS) during a 1-hour cat chamber exposure. TSS is the sum of 7 items rated from 0 - 3 (none to severe) for nasal symptoms (rhinorrhea, nasal congestion, nasal itching, and sneezing) and non-nasal symptoms (eye watering, eye itching, and itching palate/ ear/ throat).
Interventions
BIOLOGICALStandardized Allergenic Extract, Cat Hair
Standardized Cat Hair Allergenic Extract sublingual drops
BIOLOGICALPlacebo
Placebo Sublingual Drops
Sponsors
Antigen Laboratories, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients between ages of 18 and 55 years (inclusive). * Written informed consent to participate in the study. * Documented allergy to cat hair as demonstrated by a positive epicutaneous skin test (wheal \>3 mm) and symptoms of allergic rhinitis during exposure to cats. * Female subjects of childbearing potential, defined as not surgically sterile or at least 2 years postmenopausal, must agree to use one of the following forms of contraception from screening through the 4 week follow-up period following the last dose of clinical trial: hormonal begun \>30 days prior to screening, barrier, intrauterine device or vasectomized partner (6 months minimum). * No clinically significant abnormal findings on physical examination, with the exception of head, ears, eyes, nose, and throat (HEENT) findings consistent with allergic rhinitis, medical history, or clinical laboratory results during screening which would jeopardize the safety of the subject or impact validity of study results.
Exclusion criteria
* Previous allergen immunotherapy (subcutaneous immunotherapy (SCIT), oral immunotherapy, sublingual immunotherapy (SLIT) or recombinant peptide) for cat within 24 months of Screening Visit. * History of severe allergic reaction requiring medical intervention. * Intolerance of or severe allergic reaction to previous immunotherapy (SCIT, oral immunotherapy, SLIT, or recombinant peptide). * Allergy to any of the non-antigen ingredients in the study drug formulation, including, but not limited to: Food, Drug and Cosmetic Act (FD&C) Yellow #5, Red #40 and Blue #1; sodium chloride; sodium bicarbonate; and glycerine. * History of asthma requiring daily medication. * Subjects receiving anti-IgE monoclonal antibodies. * Congenital immune deficiency or acquired immune suppression. Causes of acquired immune suppression may include, but are not limited to, systemic illnesses such as malignancy and infection, the use of medications such as corticosteroids and chemotherapeutic agents, and radiation therapy. * History of organ transplant, hematologic malignancy, autoimmune disease, myocardial infarction, or congestive heart failure. * History of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, psychiatric, or cardiovascular disease, or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. * Inability or unwillingness to stop using drugs that may inhibit the wheal-and-flare reaction or rhinitic response prior to the study and for the duration of dosing clinical trial material (CTM), with the exception of protocol-specified rescue medications provided by the study site for use after Study Day 0. This includes, but is not limited to: * Decongestants for 3 days prior to Study Day 0 * H1 antagonists (antihistamines) (oral, nasal or ocular) for 7 days prior to Study Day 0 * Topical intranasal corticosteroids for 14 days prior to Study Day 0 * Cromolyn or nedocromil for 14 days prior to Study Day 0 * Systemic corticosteroids for 28 days prior to Study Day 0 * Tricyclic antidepressants for 28 days prior to Study Day 0 * Leukotriene modifiers for 7 days prior to study Day 0 * Inability or unwillingness to stop using drugs that may inhibit the ability to treat a severe allergic adverse event. This includes, but is not limited to: beta blockers such as atenolol (Tenormin®), metoprolol (Lopressor®, Toprol-XL®) and propranolol (Inderal®, Inderal LA®) for 14 days prior to Study Day 0 and for the duration of the study. * Female subjects who are trying to conceive, are pregnant, or are lactating. * Positive serum pregnancy test at screening or a positive human chorionic gonadotropin (HCG) urine test on Study Day 0 prior to administration of study drug for women of childbearing potential. * Positive blood screen for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbSAg), or Hepatitis C. * Forced Expiratory Volume in 1 second (FEV1) \<70% of the predicted value. * History of alcohol or drug abuse within the year prior to the Screening Visit, or current evidence of substance dependence or abuse. * Participation in a clinical trial or receipt of a non-FDA approved therapy within 30 days prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scores on a Scale (Average of Total Symptom Scores) | 20 weeks | Sum of individual symptoms scores, 7 items, 21 points maximum Total Symptom Scores during environmental chamber exposures at week 20. The Total Symptom Score was defined as the sum of the scores from the following seven symptoms rated 0-3 (0=absent, 1=mild, 2= moderate, 3=severe): runny nose, sneezing, itching nose, nasal congestion, watery eyes, itchy eyes, and itchy ears/palate/throat. Total Symptom score could range from 0-21; the lower the score, the more favorable the outcome. Each symptom parameter was graded by the study subject every 10 minutes for up to 60 minutes during the baseline (Day 0) and during the Week 20 environmental chamber exposures. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo - Dose Group C | 58 |
| 0.21 Units Fel d 1 Standardized Allergenic Extract, Cat Hair ( Active Dose Group A | 54 |
| 2.1 Units Fel d 1 Standardized Allergenic Extract, Cat Hair (F Active Dose Group B | 57 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 3 |
Baseline characteristics
| Characteristic | 0.21 Units Fel d 1 Standardized Allergenic Extract, Cat Hair ( | 2.1 Units Fel d 1 Standardized Allergenic Extract, Cat Hair (F | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 57 Participants | 58 Participants | 169 Participants |
| Age, Continuous | 36 years STANDARD_DEVIATION 8 | 33 years STANDARD_DEVIATION 9 | 34 years STANDARD_DEVIATION 9 | 34.5 years STANDARD_DEVIATION 9 |
| Region of Enrollment United States | 54 participants | 57 participants | 58 participants | 169 participants |
| Sex: Female, Male Female | 33 Participants | 38 Participants | 39 Participants | 110 Participants |
| Sex: Female, Male Male | 21 Participants | 19 Participants | 19 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 58 | 20 / 54 | 33 / 57 |
| serious Total, serious adverse events | 0 / 58 | 2 / 54 | 0 / 57 |
Outcome results
Primary
Scores on a Scale (Average of Total Symptom Scores)
Sum of individual symptoms scores, 7 items, 21 points maximum Total Symptom Scores during environmental chamber exposures at week 20. The Total Symptom Score was defined as the sum of the scores from the following seven symptoms rated 0-3 (0=absent, 1=mild, 2= moderate, 3=severe): runny nose, sneezing, itching nose, nasal congestion, watery eyes, itchy eyes, and itchy ears/palate/throat. Total Symptom score could range from 0-21; the lower the score, the more favorable the outcome. Each symptom parameter was graded by the study subject every 10 minutes for up to 60 minutes during the baseline (Day 0) and during the Week 20 environmental chamber exposures.
Time frame: 20 weeks
Population: Modified Intent to Treat. All subjects with at least 1 symptom assessment during post treatment chamber exposure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Scores on a Scale (Average of Total Symptom Scores) | 7.02 Scores on a scale | Standard Deviation 4.48 |
| 0.21 Units Standardized Allergenic Extract, Cat Hair | Scores on a Scale (Average of Total Symptom Scores) | 8.30 Scores on a scale | Standard Deviation 5.14 |
| 2.1 Units Standardized Allergenic Extract, Cat Hair | Scores on a Scale (Average of Total Symptom Scores) | 7.87 Scores on a scale | Standard Deviation 4.99 |
Comparison: ANOVA with baseline score as covariatep-value: <0.05ANOVA