The Impact of Grass SLIT Treatment on Birch Pollen Induced Allergic Rhinitis - a Pilot Evaluation

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.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinoconjunctivitis
• Intervention / Treatment: Drug: Grastek®; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 exclusion criteria), or gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, immunological, dermatological, connective tissue diseases or disorders, or a history of malignancy within the past 5 years, with the exception of non-melanoma skin cancer.
4. Has any significant abnormalities found during physical exam as determined by the investigator.
5. Has a current medical history of significant pulmonary disease and/or active asthma requiring daily drug therapy. Mild, intermittent asthma is permitted (managed with short acting beta-agonist less than 3 times per week). Isolated exercise-induced bronchospasm is also permitted.
6. Has received an investigational drug within the last thirty (30) days.
7. Has had use of immunotherapy containing grass or birch within the last 3 years.
8. Has significant nasal polyps, nasal septal perforation, or nasal tract malformations as noted on physical exam.
9. Administration of adrenaline (epinephrine) is contraindicated (e.g. participants with acute or chronic symptomatic coronary heart disease or concomitant beta-blocker therapy).
10. Is unlikely to cooperate with the requirements of the study including having the ability to communicate with the investigator appropriately.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Grastek®; 48 participants will receive Grastek® once per day for 120 days. Grastek® is a standardized sublingual immunotherapy (SLIT) tablet containing 2800 BAU of standardized allergen extract from Timothy grass (Phleum pretense). This SLIT product is approved by Health Canada and the Food and Drug Administration (FDA) for the treatment of grass-pollen induced allergic rhinoconjunctivitis (AR) in Canada and the United States respectively.	Drug: Grastek®; one tablet daily for four months
Placebo Comparator: Placebo; 48 participants will receive placebo once per day for 120 days.	Drug: Placebo; one tablet daily for four months; Other Names: sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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®	4 months

Collaborators and Investigators

• Sponsor: Queen's University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Anne K Ellis, MD, Queen's University

Publications and helpful links

General Publications

• Ellis AK, Tenn MW, Steacy LM, Adams DE, Day AG, Walker TJ, Nolte H. Lack of effect of Timothy grass pollen sublingual immunotherapy tablet on birch pollen-induced allergic rhinoconjunctivitis in an environmental exposure unit. Ann Allergy Asthma Immunol. 2018 May;120(5):495-503.e2. doi: 10.1016/j.anai.2018.02.003. Epub 2018 Feb 9.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: March 4, 2015
• First Submitted That Met QC Criteria: March 16, 2015
• First Posted (Estimate): March 20, 2015

Study Record Updates

• Last Update Posted (Actual): January 29, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: allergy; rhinitis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: EEU-MERCK 001