Dymista in Chinese Adolescents

Trial Design and Rationale for Trial Design:

This is a multicenter, phase 4, single arm clinical trial to evaluate the efficacy and safety of Dymista nasal spray (137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate) in the treatment of AR in Chinese adolescents with or without ocular symptoms. Because Dymista has already been approved, this trial design is selected to gather additional data on efficacy and safety of Dymista in Chinese adolescents in a close to real-world setting but under clinical oversight.

Number of Participants: Approximately 100 participants will be enrolled into the study.

Number of Arms: Single arm

Duration: Total duration of trial participation for each participant will vary from 29 to 60 days (depending on extended periods of screening, treatment, and follow-up).

This trial starts with approximately -7 to 1 day of screening period, i.e., Visit 2 (start of treatment) can eventually be on the same day of Visit 1 or up to 7 days later. Treatment period will be for 2 weeks (14+5 days) during which participants will administer Dymista nasal spray (137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate) in each nostril, twice daily (BID) and then return to the study site at Visit 3 for end of study examination on Day 15 (+5). Subsequently, participants will be followed up for any AEs for 2 weeks (14+5 days) after the last dose via phone. Once an AE is detected and ongoing, it should be followed up at least two weeks later (i.e., 28 (+5) days after last dose) until its resolution or until it is judged by the principal investigator to be stable or permanent.

Blinding: Not Applicable (No blinding).

Main Selection Criteria - Inclusion and Exclusion criteria of Trial Population:

The Inclusion Criteria for the study focus on enrolling Chinese participants aged 12-17 years who have moderate-to-severe seasonal and/or perennial AR, with or without ocular symptoms. Participants must show signs of Immunoglobulin E (IgE)-mediated hypersensitivity confirmed by diagnostic tests, have acute allergic rhinitis symptoms at inclusion, and be in general good health. They must also be able to use Dymista nasal spray correctly, agree to complete study requirements such as the patient diary, and provide informed consent/assent along with their legal guardians.

The Exclusion Criteria aim to ensure participant safety and study integrity. Individuals with known allergies to Dymista or its components, pregnant or breastfeeding females, or those unable to comply with study requirements are excluded. Additional exclusions include nasal conditions that interfere with drug delivery, recent nasal or sinus surgery, chronic sinusitis, recent use of investigational drugs or certain medications, respiratory infections, asthma (except mild intermittent), and recent immunotherapy. Individuals anticipating significant environmental changes are also excluded.

Trial Treatment:

Dymista nasal spray (137 μg of azelastine hydrochloride and 50 μg of fluticasone propionate, administered twice daily)

Inclusion criteria

• Male or female Chinese participants aged 12 to 17 years (inclusive) at screening.
• informed consent/assent from participants and from parent(s) or legal guardian(s) in compliance with local requirements.
• Participants must have moderate-to-severe seasonal and/or perennial AR with or without ocular symptoms, defined as rhinitis with one or more of the following being present:

• Sleep disturbance
• Impairment of daily activities, leisure, and/or sport
• Impairment of learning or work
• Troublesome symptoms
• Moderate to severe seasonal and/or perennial AR with or without ocular symptoms in whom intranasal antihistamines or glucocorticoid monotherapy is not considered sufficient at the discretion of the Investigator and/or designee.
• Presence of Immunoglobulin E (IgE)-mediated hypersensitivity to one or more aeroallergens present in the current participant environment, confirmed by a positive response to an established standard diagnostic test at the site within the last year (before treatment start). Accepted diagnostic tests include:

• Skin prick tests
• Specific IgE tests Diagnosis of hypersensitivity will follow the current clinical practice at study sites.
• Acute allergic rhinitis symptoms at the day of inclusion evidenced by a 12-hour reflective TNSS ≥8 out of 12.
• General good health and free of any disease or concomitant treatment that may increase the risk associated with study participation or investigational product administration or could interfere with the interpretation of the study results as determined by the Investigator or the Sponsor's medical officer. When in doubt, the Investigator should confer with the Sponsor's medical monitor or designee to determine eligibility for the study.
• Negative pregnancy test in females with childbearing potential.
• Ability to understand and follow the instructions for using Dymista nasal spray according to the participant information leaflet.
• Willingness to complete and return the Patient Diary and comply with the study requirements.

Exclusion criteria

Safety concerns:

• Known allergic reaction from and/or intolerance to Dymista, azelastine hydrochloride, fluticasone propionate nasal sprays or any of the ingredients
• Pregnancy/planned pregnancy or breastfeeding during this study

Lack of suitability for the study:

• Participants or parent(s)/legal guardian(s) are not able to fulfil study requirements according to Investigator's opinion.
• Clinically significant nasal or sinus disease that may affect intranasal drug deposition, including but not limited to nasal mucosal erosion/ulceration or septum perforation (Grade 1b - 4), significant polyposis, marked septum deviation, active or recurrent sinusitis (>3 episodes/year), or nasal/sinus surgery within the past 12 months.
• The use of any investigational drug within 30 days or within 5 half-lives of the investigational drug (whichever is longer) prior to inclusion. No other investigational products are permitted for use during the conduct of this study.
• Respiratory tract infections within 7 days prior to inclusion.
• Asthma (with the exception of mild intermittent asthma). Participants with mild intermittent asthma who only require short-acting inhaled bronchodilators and who do not have nocturnal awakening as a result of asthma are eligible for enrolment.
• Current use or expected requirement of ritonavir or strong P4503A4 inhibitors including cobicistat-containing products.
• Specific immunotherapy within 6 months prior to Screening Visit. If the participant received immunotherapy a 6-month washout period is required following the last dose of immunotherapy.
• Use of the following medications or therapies within the time period specified below prior to Screening Visit:

Medication/Therapy Time Prior to Screening Visit

• Antihistamines: including oral, ocular, intranasal, prescribed and over the counter, biological active supplements, cold preparation, sleep aids containing such components (5 days)
• Oral and intranasal anticholinergic agents including ipratropium nasal spray (5 days)
• Inhaled, oral corticosteroids (30 days)
• Intranasal corticosteroids (14 days)
• Systemic steroids, includes oral, injected, intravenous [IV], (30 days)
• Ocular corticosteroids (7 days)
• Leukotriene inhibitors (14 days)
• Oral antibiotics for Respiratory tract infections (14 days)
• Cromolyn compounds, all mast cell stabilizers (14 days)
• Ephedrine or pseudoephedrine containing products (5 days)
• Decongestants including cold preparations (5 days)
• Traditional Chinese Medicines (TCM) for treatment of AR with known active ingredient, e.g. antihistamines, ephedrine or pseudoephedrine, (5 days)
• TCM for treatment of AR with unknown active ingredient (14 days)
• Tricyclic antidepressants (30 days)
• Monoamine oxidase inhibitors (14 days)
• Immunosuppressives/immunomodulators, e.g., anti-tumour necrosis factor (TNF) agents (30 days)
• IgE antagonist or other biologics (130 days)

Administrative reasons:

• Participants anticipating significant changes in their daily environmental exposure (e.g. travel more than 3 days).