4S - Seasonal Symptoms Suppression Study

Study Overview
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Brief Summary
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ASIT naïve patients sensitized to grass pollens will be recruited for the study. All of them will be instructed to treat bothersome in-season symptoms when they appear (on as needed, pro re nata basis) with rescue medication. They will be given 5 different options and will be informed about the effects of each of them in order to make their optimal choice for different symptoms and their combination: local decongestant (xylomethazoline, when congestion is leading), local antihistamine (azelastine, when itching, sneezing and rhinorhea a predominant), nasal corticosteroid (momethasone, when all nasal symptoms are pressing and no adequate relief is obtained form the other 2 local treatments), oral antihistamine (bilastine, when itching and sneezing persist despite the local treatments) and oral corticosteroid (prednisolone, when any or all symptoms become unbearable despite the other suggested treatments). Patients who are reluctant to use immunotherapy or who are too late to initiate it will be randomized to be treated with the listed medications on as needed basis, the nasally applied formulations will be followed by either HPMC to prolong and enhance their effect (Group HPMC) or placebo (lactose powder) (Group Placebo) to serve as control. Patients indicated and willing to carry out ASIT will be treated according to the standard protocol with grass allergens sublingually (Staloral #688) and will receive rescue medication (Group Immunotherapy).

Detailed Description
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Rationale. Assessment and follow up of specifically sensitized subjects with allergic rhinitis during the pollen season is traditionally based on symptom scores. Accounting for the use of rescue medication on top of symptom scores provides another dimension to the overall clinical characterization of the patients. Thus, using combined symptom and medication scores (CSMS) allows thorough characterization of the disease course. Guidelines recommend that CSMS are used for assessment of the effect of allergen specific immunotherapy in subjects with allergic rhinitis. Different allergic rhinitis management strategies can be evaluated and compared by means of CSMS. In the update of the ARIA guidelines of 2010, 24 recommendations have been made in relation to pharmacologic treatment. Special position paper has been devoted to severe chronic upper airway disease (SCUAD), the treatment for which has been earmarked as unmet need. Consequently, a standardized and universally recognized rescue treatment strategy does not exist. The most common approach for handling nasal complaints in real life consists in using rescue medication for symptoms whenever they appear. This is certainly the case when symptoms appear for the first time ever, or when patients do not want to resort to allergen specific immunotherapy (ASIT) and / or regular oral antihistamine treatment for financial reasons or personal beliefs. Under these circumstances, a long list of pharmacological choices for local or systemic application is possible including antihistamines, corticosteroids, leukotriene antagonists, cromones and antimuscarinic drugs. Formulations for local application in the nose appeal to patients with their ease of use and immediate relief. They comprise a variety of generic drugs: decongestants, antihistamines, corticosteroids and antimuscarinics. The fact that they are not ingested makes them first choice for people reluctant to take oral medications. In many cases it is possible to control the symptoms of allergic rhinitis with these formulations used per se or as adjunct rescue medication in the course of ASIT. The question stays whether the effectiveness of nasally applied drugs can further be improved. Despite the good rationale for their mechanism of action, their efficacy is diminished by the cleaning mechanisms of the nose, rhinorrhea in particular. Slowing down of the clearance of the nasal mucosa and prolonging the contact time with the nasal mucosa would enhance their pharmaceutical effects. The investigators have demonstrated by objectively measuring nasal flow rates that sealing in place locally applied oxymetazoline in subjects with persistent allergic rhinitis by means of commercially available hydroxyl-propyl-methyl-cellulose (HPMC) significantly enhances the resulting decongestion and that this effect is augmented over a time span of 2 weeks without noticeable tachyphylaxis or adverse events. The investigators set the aim to investigate whether this beneficial effect of HPMC translates into clinical benefits in a real life clinical trial for other available drug preparations for nasal delivery. Study design. ASIT naïve patients sensitized to grass pollens will be recruited for the study. All of the patients will be instructed to treat bothersome in-season symptoms when they appear (on as needed, pro re nata basis) with rescue medication. The patients will be given 5 different options and will be informed about the effects of each of them in order to make their optimal choice for different symptoms and their combination: local decongestant (xylomethazoline, when congestion is leading), local antihistamine (azelastine, when itching, sneezing and rhinorhea a predominant), nasal corticosteroid (momethasone, when all nasal symptoms are pressing and no adequate relief is obtained form the other 2 local treatments), oral antihistamine (bilastine, when itching and sneezing persist despite the local treatments) and oral corticosteroid (prednisolone, when any or all symptoms become unbearable despite the other suggested treatments). Patients who are reluctant to use immunotherapy or who are too late to initiate it will be randomized to be treated with the listed medications on as needed basis, the nasally applied formulations will be followed by either HPMC to prolong and enhance their effect (Group HPMC) or placebo (lactose powder) (Group Placebo) to serve as control. Patients indicated and willing to carry out ASIT will be treated according to the standard protocol with grass allergens sublingually (Staloral #688) and will receive rescue medication (Group Immunotherapy).

Official Title
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Real Life Proof-of-Concept Study to Assess the Effect of Methylcellulose as add-on Seal to the In-season Pharmacologic Rescue Treatment in Subjects With Allergic Rhinitis

Conditions
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Seasonal Allergic Rhinitis

Intervention / Treatment
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* Drug: Xylometazoline - intranasal application
* Drug: Azelastine - intranasal application
* Drug: Mometasone furoate - intranasal application
* Drug: Hydroxyl-propyl-methyl cellulose powder - intranasal application
* Other: Placebo - Lactose powder
* Drug: Bilastine 20 mg
* Drug: Prednisolone 5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients Age ≥ 18 and ≤ 55 years Personal history of rhinitis during the pollen season Moderately severe / severe seasonal allergic rhinitis (grass) Positive skin prick test for grass/cereals Exclusion Criteria: Subjects with arterial hypertension, arrhythmia or evidence of heart ischemia Subjects with other serious chronic comorbidities and bad therapeutic control Subjects with nasal polyposis Any contraindications for xylometazoline Any contraindications for HPMC Any contraindications for azelastine Any contraindications for bilastine Any contraindications for mometasone Any contraindications for prednisolone Subjects unable to give informed consent Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group HPMC<br>Hydroxyl-propyl-methyl-cellulose (HPMC) powder added immediately after other intranasal treatment options | Drug: Xylometazoline - intranasal application<br>* Applied as needed up to 5 consecutive days when prominent congestion<br>Drug: Azelastine - intranasal application<br>* Applied as needed when prominent symptom is rhinorrhea<br>* Other names: Allergodil;Drug: Mometasone furoate - intranasal application<br>* Applied once daily (2 puffs) when no satisfactory therapeutic control from other intranasal treatment<br>* Other names: Nasonex;Drug: Hydroxyl-propyl-methyl cellulose powder - intranasal application<br>* Applied intranasally immediately after every application other intranasal formulation<br>* Other names: Nasaleze;Drug: Bilastine 20 mg<br>* 1 tablet per os - as needed<br>* Other names: Fortecal;Drug: Prednisolone 5 mg<br>* Per os - if needed (only in case of broncial obstruction)<br>|
| Placebo Comparator: Group Placebo<br>Lactose powder (placebo) added immediately after other intranasal treatment options | Drug: Xylometazoline - intranasal application<br>* Applied as needed up to 5 consecutive days when prominent congestion<br>Drug: Azelastine - intranasal application<br>* Applied as needed when prominent symptom is rhinorrhea<br>* Other names: Allergodil;Drug: Mometasone furoate - intranasal application<br>* Applied once daily (2 puffs) when no satisfactory therapeutic control from other intranasal treatment<br>* Other names: Nasonex;Other: Placebo - Lactose powder<br>* Applied intranasally immediately after every application other intranasal formulation<br>Drug: Bilastine 20 mg<br>* 1 tablet per os - as needed<br>* Other names: Fortecal;Drug: Prednisolone 5 mg<br>* Per os - if needed (only in case of broncial obstruction)<br>|
| Other: Group Immunotherapy<br>Immunotherapy group with grass allergens sublingually (Staloral #688) and rescue medication | Drug: Xylometazoline - intranasal application<br>* Applied as needed up to 5 consecutive days when prominent congestion<br>Drug: Azelastine - intranasal application<br>* Applied as needed when prominent symptom is rhinorrhea<br>* Other names: Allergodil;Drug: Mometasone furoate - intranasal application<br>* Applied once daily (2 puffs) when no satisfactory therapeutic control from other intranasal treatment<br>* Other names: Nasonex;Drug: Bilastine 20 mg<br>* 1 tablet per os - as needed<br>* Other names: Fortecal;Drug: Prednisolone 5 mg<br>* Per os - if needed (only in case of broncial obstruction)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Sypmtom and Medication Score | The primary outcome will be comparison of total combined symptoms and medication scores (TCSMS) collected from patients' diaries for a fixed period during the pollen season | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Specific Combined Sypmtom and Medication Score | Drug specific combined symptoms and medication scores (DsCSMS) will be calculated for each rescue medication and compared between the 3 arms of the trial. | Up to 6 months | 
| Visual Analogue Scale | Visual analogue scale (VAS) scores (Scores range from 0 [no symptoms] to 10 [worst possible symptoms]) at each visit and compared between groups. | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pollenosis, Congestion, Mucoadhesive Treatment, Nasal Decongestant, Nasal Antihistamine, Nasal Corticosteroid