Allergic Rhinoconjunctivitis
Conditions
Keywords
rhinitis, allergy
Brief summary
This pilot study is a Phase IV, single center, placebo-controlled, parallel study design conducted using the Environmental Exposure Unit (EEU). The study will aim to be determine whether there are any benefits from Grastek® for the treatment of birch-pollen induced allergic rhinoconjunctivitis. Grastek® is a Health Canada and FDA approved sublingual immunotherapy (SLIT) for the treatment of grass-pollen induced allergic rhinoconjunctivitis. The EEU provides a closed environment in which participants are exposed to a predetermined, controlled, constant level of airborne pollen. 96 participants will complete this study and will either receive Grastek® or placebo in a 1:1 ratio. The study will consist of a screening visit, a pre-treatment pollen exposure visit, 60 days of treatment with Grastek® or placebo, two treatment visits and a follow-up pollen exposure visit.
Interventions
DRUGGrastek®
one tablet daily for four months
DRUGPlacebo
one tablet daily for four months
Sponsors
Merck Sharp & Dohme LLC
Queen's University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Participant demonstrates understanding and has provided an appropriately signed and dated informed consent. 2. Male or Female, 18 to 65 years of age, at time of the Screening visit. 3. Participant has a history of at least moderate allergic rhinoconjunctivitis due to hypersensitivity to birch pollen for a minimum of 2 years. 4. Participant responds to the birch pollen and timothy grass pollen through a standard skin prick test administered at the Screening visit. A positive test will be defined as a wheal diameter at least 5mm or larger than the negative control (normal saline) wheal. A historical skin-prick test performed within three-hundred sixty-five (365) days or one (1) year at the site will be accepted in lieu of performing a new skin prick test. 5. Participant understands and is willing, able and likely to comply with study procedures and restrictions. 6. Participant, if female, has a negative urine pregnancy test at Visit 1 and is willing to use a medically acceptable form of birth control. Acceptable methods of birth control for this study include: * oral, patch, or intra-vaginal hormonal contraceptives * Norplant System® * Depo-Provera® * IUD * double barrier method * abstinence * surgically sterile females (hysterectomy or tubal ligation) * \> 1 year post-menopausal females * same sex partner * partner vasectomy (\> 3 months) 7. Participant is healthy as determined by pre-study medical history, physical examination and vital signs. 8. Participant is able to read, comprehend, and record all information in English. 9. Participant has a serum specific IgE level to both birch and timothy grass of ≥0.7 ku/L.
Exclusion criteria
1. Has significant current nasal or ocular symptoms that the study doctor associates with perennial allergic or non-allergic rhinitis. 2. Female participant who is pregnant or lactating. 3. Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study. This includes a clinically relevant medical or surgical history or presence of other respiratory disease (exceptions made for asthma and allergic rhinitis as defined in further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Nasal Symptom Score (TNSS) From Baseline to Post-treatment. | 4 months | To determine the effect of 4 months of treatment with Grastek® on the symptoms of birch pollen induced AR in participants with both timothy grass pollen-induced and birch pollen-induced allergen rhinitis (AR) TNSS is comprised of the sum of 4 symptoms: runny nose, itchy nose sneezing and nasal congestion. Each of these symptoms are evaluated based on a 4 point Likert scale from 0-3. 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. TNSS can therefore have a range from 0 to 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of Blood Samples for Potential Biomarkers by Comparing Baseline and Post-treatment Samples. | 4 months | To determine potential biomarkers predictive of clinical efficacy for birch pollen-induced AR following treatment with Grastek® |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Grastek 4 months of once per day Grastek sublingual immunotherapy | 47 |
| Placebo 4 months of once per day matching placebo sublingual tablet | 46 |
| Total | 93 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Grastek | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants | 45 Participants | 46 Participants |
| Age, Continuous | 38.03 years | 37.89 years | 38.17 years |
| Region of Enrollment Canada | 93 Participants | 47 Participants | 46 Participants |
| Sex: Female, Male Female | 48 Participants | 25 Participants | 23 Participants |
| Sex: Female, Male Male | 45 Participants | 22 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 47 | 23 / 46 |
| serious Total, serious adverse events | 0 / 47 | 1 / 46 |
Outcome results
Primary
Change in Total Nasal Symptom Score (TNSS) From Baseline to Post-treatment.
To determine the effect of 4 months of treatment with Grastek® on the symptoms of birch pollen induced AR in participants with both timothy grass pollen-induced and birch pollen-induced allergen rhinitis (AR) TNSS is comprised of the sum of 4 symptoms: runny nose, itchy nose sneezing and nasal congestion. Each of these symptoms are evaluated based on a 4 point Likert scale from 0-3. 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. TNSS can therefore have a range from 0 to 12.
Time frame: 4 months
Population: 93 participants were randomized into this study. The final number of participants that completed and were included for analysis are listed above.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Grastek | Change in Total Nasal Symptom Score (TNSS) From Baseline to Post-treatment. | 2.3 Scores on a scale |
| Placebo | Change in Total Nasal Symptom Score (TNSS) From Baseline to Post-treatment. | 2.2 Scores on a scale |
Secondary
Analysis of Blood Samples for Potential Biomarkers by Comparing Baseline and Post-treatment Samples.
To determine potential biomarkers predictive of clinical efficacy for birch pollen-induced AR following treatment with Grastek®
Time frame: 4 months
Population: As the primary outcome showed that there was no significant difference between Grastek and placebo this outcome was not able to be completed.