Safety and Efficacy Study of PA9159 Nasal Spray for the Treatment of Seasonal Allergic Rhinitis

NCT05234580 | Completed Phase 2

• 1 other identifier: PA9159-201
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 17

Brief Summary

PA9159 is a highly potent novel corticosteroid. The purpose of this study is to evaluate the safety, efficacy and characteristics of population pharmacokinetics of multiple dosing of PA9159 Nasal Spray in patients with seasonal allergic rhinitis.

Conditions

Allergic Rhinitis

Keywords

Seasonal Allergic Rhinitis

Outcome Measures

Primary Outcomes (1)

• 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 1. = mild 2. = moderate 3. = 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 (16)

• Evaluation the proportion and frequency of patients using the antihistamine drug of loratadine tablets during the treatment period;

  From pre-dose until 14 days post-dose

• Evaluation the change from baseline in daily subject-reported AM and PM Instantaneous Total Nasal Symptoms Scores (iTNSS) averaged over the 14-day treatment period.

  From pre-dose until 14 days post-dose

• Evaluation the Area Under the Curve (AUC) of Reflective Total Nasal Symptom Score (rTNSS) over time in subjects.

  From pre-dose until 14 days post-dose

• Evaluation the change from baseline in subject-reported Instantaneous Total Nasal Symptoms Scores (iTNSS) at 4 h ± 0.5 h, 8 h ± 0.5 h, and 12 h ± 1 h after the first dose in the treatment period.

  Day 1 of the first dose

• Evaluation the change from baseline in daily subject-reported AM Reflective Total Nasal Symptom Score (rTNSS) averaged over the 14-day treatment period.

  From pre-dose until 14 days post-dose

Study Arms (4)

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.

Drug: Placebo nasal spray solution without PA9159, once daily for 14 days

Interventions

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.

PA9159 10 μg

PA9159 nasal spray solution, 20 μg once daily for 14 days DRUG

PA9159 of 20 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

PA9159 20 μg

PA9159 nasal spray solution, 40 μg once daily for 14 days DRUG

PA9159 of 40 μg is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

PA9159 40 μg

Placebo nasal spray solution without PA9159, once daily for 14 days DRUG

Placebo nasal spray solution is delivered intranasally through a metered-dose mechanical spray pump, once daily in the morning for 14 days.

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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;
• Signs: pallor and edema of the nasal mucosa and watery nasal secretions;
• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• Anhui Palo Alto Pharmaceuticals, Inc.: lead

Study Sites (17)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

Location

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

Location

Beijing Shijitan Hospital

Beijing, Beijing Municipality, China

Location

Beijing TongRen Hospital

Beijing, Beijing Municipality, China

Location

Dongfang Hospital Beijing University of Chinese Medicine

Beijing, Beijing Municipality, China

Location

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Location

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, China

Location

The Affiliated Hospital of Changchun University of Chinese Medicine

Changchun, Jilin, China

Location

Tonghua Central Hospital

Tonghua, Jilin, China

Location

Yanbian University Hospital(Yanbian Hospital)

Yanji, Jilin, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Location

Yantai Yuhuangding Hospital

Yantai, Shandong, China

Location

Zibo Central Hospital

Zibo, Shandong, China

Location

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Location

Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, China

Location

Tianjin People's Hospital

Tianjin, Tianjin Municipality, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Rhinitis, Allergic; Rhinitis, Allergic, Seasonal

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Luo Zhang, phD

  Beijing Tongren Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 10, 2022
• Study Start: April 15, 2022
• Primary Completion: October 10, 2022
• Study Completion: December 25, 2022
• Last Updated: February 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (17)