Safety and Efficacy Study of PA9159 Nasal Spray for the T... | NCT05234580

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PA9159 10 μg	Experimental	Fifty subjects will be randomly assigned to receive 10 μg of PA9159 Nasal Spray for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 5 μg/spray; Spray Bottle B: 0 μg/spray.	Drug: PA9159 nasal spray solution, 10 μg once daily for 14 days
PA9159 20 μg	Experimental	Fifty subjects will be randomly assigned to receive 20 μg of PA9159 Nasal Spray for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 0 μg/spray; Spray Bottle B: 10 μg/spray.	Drug: PA9159 nasal spray solution, 20 μg once daily for 14 days
PA9159 40 μg	Experimental	Fifty subjects will be randomly assigned to receive 40 μg of PA9159 Nasal Spray for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 10 μg/spray; Spray Bottle B: 10 μg/spray.	Drug: PA9159 nasal spray solution, 40 μg once daily for 14 days
Placebo	Placebo Comparator	Fifty subjects will be randomly assigned to receive placebo Nasal Spray without active of PA9159 for 14 days. Subjects will be administered two vials of drug (spray bottle A and spray bottle B) once daily in the morning, one spray each in the left and right nostril, in the order of first spray A and then spray B. Spray Bottle A: 0 μg/spray; Spray Bottle B: 0 μg/spray.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PA9159 nasal spray solution, 10 μg once daily for 14 days	Drug	PA9159 of 10 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Evaluation the change from baseline in daily subject-reported AM and PM Reflective Total Nasal Symptom Score (rTNSS) averaged over the 14-day treatment period.	Total Nasal Symptom Score (TNSS) is the sum of individual symptoms of runny nose, sneezing, itchy nose, and nasal congestions. Subjects assess each individual symptoms on a scale of 0-3 where: 0 = absent = mild = moderate = severe Therefore, Total Nasal Symptom Score (TNSS) values range from 0-12 (with 0 representing an absence of symptoms and higher scores reflecting more severe symptoms). The parameter of Reflective Total Nasal Symptom Score (rTNSS) measures these symptoms over the previous 12-hour time interval. Difference was calculated as the 14-day treatment average - baseline. Greater reductions in the change from baseline score indicate greater improvement.	From pre-dose until 14 days post-dose

Secondary Outcomes

Measure	Description	Time Frame
Evaluation the proportion and frequency of patients using the antihistamine drug of loratadine tablets during the treatment period;	If the subject is intolerant of symptoms, loratadine tablets may be taken with the consent of the investigator, 10 mg once a day, without overdose; If symptoms improve, they will no longer be used; It can be used once or continuously for ≤ 3 days, preferably avoiding intermittent use. Continue study drug while taking salvage medication.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥ 12 years, male or female;
Clinical diagnosis is based on the Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (2018 Edition) issued by the Rhinology Group of the Otorhinolaryngology Head and Neck Surgery Branch of the Chinese Medical Association, with a clear history of Seasonal Allergic Rhinitis (SAR) ≥ 1 year (written or verbal confirmation), and positive test for one or more allergens before randomization. Recognize the results of any one of the skin prick test (SPT), intradermal test, and serum specific IgE test; Clinical manifestations may include:
1. Symptoms: 2 or more symptoms such as sneezing, runny nose, itchy nose and nasal congestion, lasting or accumulating for more than 1 h each day, may be accompanied by ocular symptoms such as itching, lacrimation, and red eyes;
2. Signs: pallor and edema of the nasal mucosa and watery nasal secretions;
3. Allergic symptoms are characterized by seasonal onset in spring and/or fall, and at the time of this enrollment, it is during the onset of symptoms.
Reflective Total Nasal Symptom Score (rTNSS) ≥ 6 points, nasal congestion ≥ 2 points, and one of the three symptoms of sneezing, runny nose and itchy nose ≥ 2 points, all these three conditions are met simultaneously at the time of screening, baseline and the first dosing during treatment; The mean rTNSS at baseline was the mean of a total of 8 scores on evening of D-4, morning and evening of D-3, D-2 and D-1, and the morning of D1;
Capable of demonstrating the correct use of nasal spray techniques after training at screening;
Capable of performing respiratory exercise as required at the time of intranasal administration after training at screening;
Is willing to sign the informed consent form (ICF), comply with the study procedures, including the correct use of the nasal spray device, and understand and accurately record the patient diary card; Ability to understand and receive treatment, laboratory tests, and other study procedures as planned.

Exclusion Criteria:

Previous intolerance to intranasal administration;
Patients with asthma requiring long-term treatment (patients with occasional acute asthma, or mild, exercise-induced asthma requiring no medication or only beta-agonist treatment during the study may be included);
Active or inactive tuberculosis infection, untreated local or systemic fungal, bacterial, viral, or parasitic infection;
Presence of glaucoma, cataract, ocular herpes simplex, infectious conjunctivitis, or other ocular infections (except allergic conjunctivitis);
Any nasal mucosal erosion, septal ulceration, or nasal septal perforation at screening or prior to the first dose on D1;Presence of other nasal disorders that may affect intranasal drug deposition as judged by the investigator, such as acute or chronic sinusitis, drug-induced rhinitis, nasal polyps, or nasal septal deviation;
History with sinus surgery within 3 months or nasal trauma that have not completely healed;
Respiratory tract infections treated with antibiotics within 4 weeks prior to screening;
Patients with severe lung diseases, such as COPD (chronic obstructive pulmonary disease), etc.;
Patients with unstable heart disease with drug-control;
Patients who have received desensitization therapy within 6 months prior to screening;
Severe liver and kidney disease, or abnormal liver and kidney function tests (ALT, AST ≥ 2 times the upper limit of normal, or Cr > 1.2 times the upper limit of normal);
Use of short-lasting prescriptions and OTC antihistamines within 3 days prior to screening; Use of nasal glucocorticoids within four weeks; Inhalation, oral, intramuscular/intravascular injection, topical hormones (except hydrocortisone cream containing ≤ 1%) within 8 weeks prior to screening; Use of nasal or ophthalmic cromoglycic acid within 14 days prior to screening; Use of long-lasting antihistamines such as loratadine, desloratadine, fexofenadine, or cetirizine within 10 days prior to screening; Oral or nasal decongestants, nasal anticholinergics, or oral antileukotrienes within 72 h prior to screening; Use of Omalizumab subcutaneously within 5 months prior to screening; Use of anti-allergic Chinese herbal medicines within 14 days prior to screening.
Planned use of the following medications or/and treatments during the study: a. Strong CYP3A4 inhibitors, such as ketoconazole, clarithromycin, etc.; b. Chronic or intermittent use of inhaled, oral, intramuscular, intravenous, and/or potent topical corticosteroids; c. Antihistamines (except salvage medications required during the trial); d. Leukotriene modulators; e. Mast cell membrane stabilizers (including cromoglycate sodium, nidolate sodium, tetrazolone, nedocromil sodium, pemirolast potassium, and tranilast, etc.); f. Decongestants; g. Anticholinergics; h. Immunotherapeutic agents; i. Anti-allergic Chinese herbal medicine;
Planned to travel outside the local area for 2 consecutive days (48 h) or a total of more than 3 days during the trial;
Alcohol addicts in the previous 1 year (alcoholism defined as: greater than 14 units of alcohol per week;1 unit of alcohol ≈ 360 mL of beer or 45 mL of spirits or 150 mL of wine containing 40% alcohol), drug abusers, drug addicts, or smoking addicts (average of more than 10 cigarettes per day);
Allergic to the investigational drug and its excipients;
Pregnant or lactating women, and male subjects (or their partners) or female subjects who have a pregnancy plan throughout the trial and for 3 months after the end of the study;
Participated in other drug clinical trials within 3 months prior to screening, and used the study drug;
Based on the judgment of the investigator, the subject may have an impact on compliance with any aspect of the protocol (including visit plan and completion of diary cards or questionnaires) due to physical, educational level, or geographic location;
Based on the opinion of the investigator, there are any circumstances that may affect the subject's informed consent or compliance with the protocol, or that the subject's participation in the trial may affect the results of the study or their own safety.

Facility	Status	City	State	ZIP	Country	Contacts
The First Affiliated Hospital of Bengbu Medical College		Bengbu	Anhui		China
The Second Hospital of Anhui Medical University

ID	Term
D065631	Rhinitis, Allergic
D006255	Rhinitis, Allergic, Seasonal

ID	Term
D012220	Rhinitis
D009668	Nose Diseases
D012140	Respiratory Tract Diseases
D012130	Respiratory Hypersensitivity
D010038	Otorhinolaryngologic Diseases
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases